Recommendations by the Spanish Society of Rheumatology on Osteoporosis

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array:1 [ 0 => array:4 [ "autoresLista" => "Antonio Naranjo Hernández, Petra Díaz del Campo Fontecha, María Pilar Aguado Acín, Luis Arboleya Rodríguez, Enrique Casado Burgos, Santos Castañeda, Jordi Fiter Aresté, Laia Gifre, Carmen Gómez Vaquero, Gloria Candelas Rodríguez, Félix Manuel Francisco Hernández, Núria Guañabens Gay" "autores" => array:12 [ 0 => array:4 [ "nombre" => "Antonio" "apellidos" => "Naranjo Hernández" "email" => array:1 [ 0 => "anarher@gobiernodecanarias.org" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Petra" "apellidos" => "Díaz del Campo Fontecha" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "María Pilar" "apellidos" => "Aguado Acín" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "c" "identificador" => "aff0015" ] ] ] 3 => array:3 [ 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Hospital Universitario La Paz, Madrid, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Sección de Reumatología, Hospital Universitario Central de Asturias, Oviedo, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "Servicio de Reumatología, Hospital Universitari Parc Taulí (UAB), Sabadell, Barcelona, Spain" "etiqueta" => "e" "identificador" => "aff0025" ] 5 => array:3 [ "entidad" => "Servicio de Reumatología, IIS Princesa, Madrid, Spain" "etiqueta" => "f" "identificador" => "aff0030" ] 6 => array:3 [ "entidad" => "Servicio de Reumatología, Hospital Universitario Son Espases, Palma de Mallorca, Spain" "etiqueta" => "g" "identificador" => "aff0035" ] 7 => array:3 [ "entidad" => "Servicio de Reumatología, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain" "etiqueta" => "h" "identificador" => "aff0040" ] 8 => array:3 [ "entidad" => "Servicio de Reumatología, Hospital Universitari de Bellvitge, Hospitalet de Llobregat, Barcelona, Spain" "etiqueta" => "i" "identificador" => "aff0045" ] 9 => array:3 [ "entidad" => "Servicio de Reumatología, Hospital Clínic, Barcelona, Spain" "etiqueta" => "j" "identificador" => "aff0050" ] 10 => array:3 [ "entidad" => "Servicio de Reumatología, Hospital Universitario Clínico San Carlos, Madrid, Spain" "etiqueta" => "k" "identificador" => "aff0055" ] 11 => array:3 [ "entidad" => "Grupo de Revisores de Evidencia de la SER, Madrid, Spain" "etiqueta" => "l" "identificador" => "aff0060" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Recomendaciones de la Sociedad Española de Reumatología sobre osteoporosis" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1331 "Ancho" => 2500 "Tamanyo" => 190050 ] ] "descripcion" => array:1 [ "en" => "Recommendations to initiate prophylaxis or Op treatment in patients who will receive glucocorticoids in the following 3 months." ] ] ] "textoCompleto" => "Introduction and objectivesOsteoporosis (OP) is a diffuse skeletal disorder characterised by a general reduction in bone strength leading to a higher risk of fracture due to fragility.In Spain and in other countries the rate of fragility fractures is increasing, mainly due to higher life expectancies.<a class="elsevierStyleCrossRef" href="#bib1000">1</a> One study reported that in 2010 2.4 million Spaniards (1.9 million women and 0.5 men) over 50 suffered from OP,<a class="elsevierStyleCrossRef" href="#bib1005">2</a> and as a consequences of this there were 204,000 new fractures at a cost of 2842 million euros (2.8%of the total healthcare costs in Spain).<a class="elsevierStyleCrossRef" href="#bib1010">3</a> It has been estimated that in 2025 there will be an 40% increase in the rate of fractures and a 30% increase in costs.<a class="elsevierStyleCrossRef" href="#bib1010">3</a>Recent years have witnessed advances in the diagnosis and treatment of OP but only a minority of patients with high fracture risk are being accurately assessed and treated in keeping with the recommendations of clinical practice guidelines.<a class="elsevierStyleCrossRef" href="#bib1015">4</a>This document contains the updated recommendations of the Spanish Society of Rheumatology (Spanish acronym: SER) on OP from the previous ones of 2011.<a class="elsevierStyleCrossRef" href="#bib1020">5</a> These recommendations aim at helping physicians take decision for the management of post-menopausal OP and secondary OP (glucocorticoids, inflammatory diseases, OP of the male and other clinical forms).MethodologyDesignQualitative synthesis of scientific evidence and consensus techniques have been used in this project which reflect the agreement by experts based on their clinical experience and scientific evidence.Procedural stagesA series of steps were taken during the development of the recommendations document, which were:<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005">1.Creation of the work group. The document began with the formation of a panel of experts formed by 9 SER member rheumatologists. They were selected through an open call to all SER members. The Clinical practice Guideline and Recommendations Committee (Spanish acronym: GPC) of the SER assessed the curriculum vitae of all applicants, in accordance with objective criteria of contribution to knowledge on OP, taking into consideration publications in significant journals over the last 5 years. Coordination of clinical and methodological aspects was made, respectively, by one of these rheumatologists as the main researcher (MR) and a methodology specialist executive from the Research Unit of the SER.</li><li class="elsevierStyleListItem" id="lsti0010">2.Identification of the key areas for updating of the previous agreement. All workgroup members were involved in giving shape to the document, and in establishing its content and key aspects. First they identified the clinical questions of research which could have the greatest impact in offering information on OP management: diagnosis, assessment, prevention, treatment and special circumstances. After this, they decided which of these required a response through the formulation of a PICO question (patient, intervention, comparison, and outcome). The methodology to be followed in the recommendation creation process was also defined.</li><li class="elsevierStyleListItem" id="lsti0015">3.Literature review search. To respond to the non PICO clinical questions an updated systematic review (SR) search and GPC was made in MEDLINE and specialised sources in guidelines. The other clinical questions were reformatted in four questions with the PICO format. To respond to the PICO questions a search strategy was designed and a review of scientific evidence was made of studies published up until May 2017. The following databases were used: PubMed (MEDLINE), EMBASE and Cochrane Library (Wiley Online). The process was completed with a reference manual, posters and congress abstracts search which the reviewers and experts considered to be of interest.</li><li class="elsevierStyleListItem" id="lsti0020">4.Analysis and synthesis of scientific evidence. The SR and GPC identified for the non PICO questions were assessed by the methodology coordinator. It was agreed that only those of high quality were considered apt for their incorporation as a source of evidence. Two rheumatologists from the workgroup of SER evidence reviewers were responsible for systematically reviewing the scientific evidence available for the PICO questions. After a critical reading of the complete test of the selected studies for each review, they drew up a summary using a homogenised formula including tables and texts to describe the methodology, results and quality of each study. They made in-depth notes on the reasons for exclusion of articles not included in the selection. The overall level of the scientific evidence was assessed using the Scottish Intercollegiate Guidelines Network (SIGN) (see <a class="elsevierStyleCrossRef" href="#sec0235">Appendix 1</a>) evidence levels.</li><li class="elsevierStyleListItem" id="lsti0025">5.Formulation of recommendations. When the critical reading was completed, the MR and the panel of experts proceeded with the formulation of specific recommendations based on the available scientific evidence. This formulation was based on “formal assessment” or “reasoned judgement,” previously summarising the evidence for each of the clinical questions. They also took into account quality, quantity and consistency of the scientific evidence, the generality of the results, its applicability and its clinical impact. For the formulation of the recommendations two rounds of consensus were used. First, with the “reasoned judgement” system, where all of the experts drafted and discussed the recommendations. Then, in the presence of the methodologist, using the modified technique of nominal consensus, the level of agreement of the experts with the drafting of each recommendation was agreed upon. It was established that there was a high level of consensus when the percentage of experts who agreed with the recommendation draft was 75% or above. The agreement was evaluated using a dichotomous reply (yes: agreed with the wording; no: disagreed with the wording). Grading of the recommendations was made with the SIGN system (see <a class="elsevierStyleCrossRef" href="#sec0235">Appendix 1</a>). The recommendations were divided into four main areas: diagnosis and evaluation; treatment; special circumstances; new treatments.</li><li class="elsevierStyleListItem" id="lsti0030">6.Public exposure. The draft of this document of SER recommendations was submitted to a process of public exposure by the members of SER and different interest groups (pharmaceutical industry, other scientific societies and patient associations) aimed at receiving scientific evaluation and discussion of its methodology and recommendations. The complete information of this process is found in the appendix to the SER web site (<a href="http://www.ser.es/">www.ser.es</a>), in the section under SER Research and Recommendations.</li></ul>StructureThe document includes all the formulated recommendations subdivided into the different above-mentioned areas. Management algorithms were formulated from the recommendations and these offer a summarised approach to the treatment of OP.ResultsThere is a total of 28 formulated recommendations on OP (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 1</a>).<elsevierMultimedia ident="tbl0015"></elsevierMultimedia>Diagnosis and evaluationDefinition and diagnosisOP is a diffuse skeletal disease characterised by a reduction in bone resistance which leads to a higher risk of fragility fractures. The concept of “bone resistance” encompasses factors relating both to bone mineral density (BMD) and the quality of the bone tissue.<a class="elsevierStyleCrossRef" href="#bib1025">6</a>A fragility fracture is that brought on by a low impact trauma. A fall, standing up or being seated would be included in this concept. The most frequent and relevant fractures are those of the proximal femur, the spine and the distal forearm.<a class="elsevierStyleCrossRef" href="#bib1030">7</a>OP may be defined in any of the following circumstances:<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0035">a)T-score in spine columnar, femoral neck or total hip ≤−2.5 SD.</li><li class="elsevierStyleListItem" id="lsti0040">b)Femoral fracture due to fragility, regardless of the BMD value, in postmenopausal women and in men >50 years of age.</li><li class="elsevierStyleListItem" id="lsti0045">c)Fracture due to fragility of the spine, proximal humerus or pelvis in postmenopausal women and in men >50 years of age, if there is a low BMD (T-score <−1.0SD).</li></ul>The conceptual definition of OP by the World Health Organisation (WHO) is solely based on the results of the BMD. An individual has OP if the T-score in lumbar spine, femoral neck or total hip is equal to or under −2.5 standard deviation (SD) compared with the population peak bone mass.<a class="elsevierStyleCrossRefs" href="#bib1035">8,9</a>In normal clinical practice this definition fails to be operative due to many fragility fractures occurring in patients with a T-score >−2.5 SD. For this reason the National Bone Health Alliance has proposed the consideration diagnosing OP in postmenopausal women and in men >50 years of age with femoral fracture caused by fragility, regardless of the BMD value, and also when there is a low impact spinal fracture, of the proximal humerus or the pelvis, if the T-score <−1.0 SD.<a class="elsevierStyleCrossRef" href="#bib1045">10</a> Doubts exist regarding forearm fracture, which in some cases could be included depending on age or the mechanism of the fracture. The authors also included OP diagnosis for the American population a quantified risk with the Fracture Risk Assessment (FRAX®) for the primary fracture ≥20% (proximal humerus, forearm, hip or clinical spine fracture) or a risk of femoral fracture ≥3%.<a class="elsevierStyleCrossRef" href="#bib1045">10</a>In view of the recommendations of these groups of experts and in accordance with clinical experience, the panel of experts considered it appropriate to include postmenopausal women and men >50 years of age with fragility fracture of the femur (regardless of BMD) in the OP diagnosis, as well as spinal fracture, fracture of the humerus or the pelvis, if it was accompanied by low bone mass (AL: 89%).Fracture risk factorsThe main aim in OP management is fracture prevention and it is therefore essential to identify those individuals with the highest risk of presenting with them.<a class="elsevierStyleCrossRef" href="#bib1050">11</a><a class="elsevierStyleCrossRef" href="#tbl0020">Table 2</a> describes high fracture risk factors (RF) (relative risk ≥2) and moderate RF (relative risk 1–2).<a class="elsevierStyleCrossRef" href="#bib1020">5</a><elsevierMultimedia ident="tbl0020"></elsevierMultimedia>Several risk factors, such as age, fracture history and the use of glucocorticoids, among others contribute to the risk of fracture regardless of the BMD. Patients with a recent fracture are at a particularly high risk of suffering from a new fracture.<a class="elsevierStyleCrossRef" href="#bib1050">11</a>The term “imminent fracture risk” has recently been proposed to refer to patents with a short term highs risk, such as those with a recent fracture, elderly fragile people with frequent falls or people treated with glucocorticoids at high level doses.<a class="elsevierStyleCrossRefs" href="#bib1055">12,13</a>Recommendation:It is recommended that evaluation of fracture risk due to fragility should not be exclusively based on BMD figures but also bear in mind clinical risk factors (RR: B; AL: 100%).The combination of the BMD with clinical RF provides the best estimation of fracture risk.<a class="elsevierStyleCrossRefs" href="#bib1065">14,15</a> This has led to the development of fracture risk calculation tools which are able to include many factors. Among the most popular and widely used is the FRAX®.<a class="elsevierStyleCrossRef" href="#bib1040">9</a>Evaluation of fracture riskRecommendation:It is recommended that the tool FRAX®be used, with or without BMD, to assess the fracture risk (RR: √; AL: 78%).The FRAX® calculates the probability of presenting a primary fracture (this include hip, clinical spine, humerus and forearm) or a hip fracture in the following 10 years, with the inclusion or non inclusion of the BMD score. When the BMD is included in the FRAX® tool the prediction of fracture risk is more precise and reliable.<a class="elsevierStyleCrossRefs" href="#bib1075">16,17</a>FRAX® limitations are mostly determined by insufficiencies in the data from which it was calculated. Thus the FRAX® does not consider the dose-response factor for several RF, nor lumbar BMD, nor the greater risk of fracture in patients with a recent fracture, and it does not encompass falls.<a class="elsevierStyleCrossRefs" href="#bib1040">9,16–18</a>The Spanish version of the FRAX® underestimates the risk of the primary fracture.<a class="elsevierStyleCrossRef" href="#bib1090">19</a> However, the application of a decision algorithm with bone densimetry threshold indication (DXA) and treatment based on FRAX® has been shown to be cost-effective with regard to the exclusive use of T-score −2.5SD.<a class="elsevierStyleCrossRef" href="#bib1095">20</a> Despite its limitations, the current version of the Spanish FRAX® may help to classify patients better with regard to fracture risk.Recommendation:It is recommended that patients be classified as high fracture risk when the risk quantified by FRAX®for hip fracture is ≥3% (RR: √; AL: 100%).Recommendation:To classify patients as high risk using the FRAX®for the primary fracture it is suggested that the threshold ≥10% without BMD be used or ≥7.5% with BMD (RR: √; AL: 78%).The validity of the Spanish FRAX® was analysed in two prospective cohorts studies and in both the primary fracture risk was underestimated. The relationship between observed fractures and expected fractures was 2.2 in the FRIDEX<a class="elsevierStyleCrossRef" href="#bib1095">20</a> study and 1.5 in the ECOSAP<a class="elsevierStyleCrossRef" href="#bib1100">21</a> Study. However, the estimation of the Spanish FRAX® for hip fracture appears to be appropriate. A workgroup estimated the thresholds of the FRAX® in the Spanish population<a class="elsevierStyleCrossRefs" href="#bib1095">20,22,23</a> defining high primary fracture risk as a FRAX®, with or without BMD, ≥7.5% and intermediate risk between 5% and 7.5%. This was a single study which defined risk thresholds in Spain and had methodological limitations such as not being validated in regions other than Catalonia, including only 8.9% of subjects with intermediate risk and 8.5% with high fracture risk, as well as overlapping in the confidence interval of the high risk threshold. In this sense, the panel considers that a women aged around 70 years with a prior fracture (is approximately equivalent to as Spanish FRAX® for the principal fracture without BMD of 10%) is an example of high fracture risk.From the scarce evidence and low level of agreement in classifying the patient as high fracture risk based on the FRAX®, the panel of experts agreed to consider a high risk fracture as FRAX® ≥3% for a hip fracture. Since no further studies on the FRAX® thresholds and/or national official positioning were available, the panel of experts also considered high fracture risk a FRAX® for primary fracture ≥10% without BMD or ≥7.5% with BMD.The panel of experts also considered as high fracture risk, but without reaching an acceptable level of agreement (AL: 55%), the combination of two or more high RF. Should the FRAX® tool not be used, the presence of two high risk factors may serve as the starting point for assessing the BMD.Bone densimetryThe technique of choice today for measuring BMD is the DXA dual energy X-ray absorptiometry.<a class="elsevierStyleCrossRefs" href="#bib1025">6,10,11</a> The measurement is made in the lumbar spine and the proximal femur (femoral neck and total hip). According to the experts, measurement using DXA of the distal third of the forearm should only be performed when measurement in the lumbar spine or the proximal femur is not feasible and/or in specific pathologies such as hyperparathyrodism.<a class="elsevierStyleCrossRef" href="#bib1115">24</a>The DXA has a high specificity for the reduction of fracture risk, but a low sensitivity. The risk increases exponentially as the BMD descends.<a class="elsevierStyleCrossRef" href="#bib1120">25</a> However, the majority of fragility fractures occur in patients with a T-score above −2.5 SD. Studies made in patients diagnosed with OP using DXA and without other RF of fractures conclude that it could be appropriate to estimate risk using FRAX® before evaluating treatment.<a class="elsevierStyleCrossRefs" href="#bib1125">26,27</a>Different groups of experts agree that the BMD determined in the peripheral skeleton using DXA of the phalanx and heel spur and the ultrasound technique of the heel spur may be useful for prediction of fracture risk but not for diagnosing OP.<a class="elsevierStyleCrossRefs" href="#bib1135">28,29</a>Bone densitometry indicationsCriteria for requesting a DXA vary widely nationally and internationally. The majority of international guidelines on OP recommend evaluation of BMD in postmenopausal women ≥65 years of age, regardless of other RF.<a class="elsevierStyleCrossRefs" href="#bib1145">30–32</a> There is controversy regarding the screening age in males. The National Osteoporosis Foundation (NOF) and the International Society for Clinical Densitometry (ISCD) recommend measurement in males ≥70 years of age, whilst the Canadian guidelines put the threshold at ≥65 years of age.<a class="elsevierStyleCrossRef" href="#bib1150">31</a>According to the conclusions of a cross-sectional study the aim of which was to evaluate DNX indication criteria in postmenopausal Spanish women based on the FRAX® tool, the indication of the test should be based on clinical criteria to allow for patients to be selected where its evaluation is more efficient.<a class="elsevierStyleCrossRef" href="#bib1160">33</a> The authors conclude that the strategy should begin with calculation of the fracture risk according to clinical RF, and in this setting using FRAX®<a class="elsevierStyleCrossRef" href="#bib1160">33</a> could be helpful.Based on the accepted international recommendations on DXA indications, the panel of experts considers that its main applications in clinical practice are: OP diagnosis, evaluation of fracture risk, evaluation of treatment and monitorisation of response to treatment.In patients with an imminent risk of fracture performing a DXA should not impede treatment initiation. Thus patients with a high fracture risk may be treated without the need to carry out a DXA, although it seems appropriate to know the baseline BMD for evaluation of treatment effectiveness at a later date. The panel of experts agree that when the fracture risk is low no DXA should be performed and that a DNA should not be recommended to all women going through the menopause.Recommendation:It is recommended to perform a densitometry in the following cases (RR: D):<ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0050">1.Fragility fracture (AL: 100%).</li><li class="elsevierStyleListItem" id="lsti0055">2.Presence of two or more high risk fracture factors (AL: 100%).</li><li class="elsevierStyleListItem" id="lsti0060">3.FRAX®for primary fracture ≥5% (AL: 78%).</li><li class="elsevierStyleListItem" id="lsti0065">4.Treatment with aromatase inhibitor drugs, antiandrogens and glucocorticoids (AL: 100%).</li><li class="elsevierStyleListItem" id="lsti0070">5.Diseases associated with secondary OP (AL: 100%).</li></ul>Based on these international studies, the panel of experts considered the use of FRAX® without BMD as initial assessment of fracture risk. When the risk calculated using the Spanish FRAX® without BMD, for the principal fracture is ≥5% it is advisable to perform DXA.<a class="elsevierStyleCrossRef" href="#bib1165">34</a> Low risk patients are therefore not recommended to have DXA.The panel also considered measuring in BMD, regardless of age, in the population which present with RF for fragility fractures such as: previous fragility fracture, women who begin treatment with aromatase inhibitors for breast cancer,<a class="elsevierStyleCrossRef" href="#bib1170">35</a> males treated with androgen deprivation therapy for prostate cancer and patients treated with glucocorticoids. The recent guideline of the American College of Rheumatology (ACR) for the prevention and treatment of OP using glucocorticoids recommends performing DXA in patients who start chronic treatment with glucocorticoids in the following cases: (1) adults <40years of age when there is a background of fracture or high RF of fracture and (2) adults ≥40 years of age in all cases and calculate the FRAX® with BMD.<a class="elsevierStyleCrossRef" href="#bib1175">36</a> the oncology guidelines and those of the International Osteoporosis Foundation (IOF) recommend DXA to decide whether to initiate treatment for OP in women receiving aromatase inhibitors<a class="elsevierStyleCrossRef" href="#bib1170">35</a> and in males in androgen deprivation therapy.<a class="elsevierStyleCrossRef" href="#bib1180">37</a>In cases of recent fracture due to fragility or treatment with high doses of glucocorticoids, studies concluded that performing a DXA should not delay initiation of treatment to prevent new fractures.<a class="elsevierStyleCrossRefs" href="#bib1055">12,13</a>Other patients who are eligible for DXA due to presenting with high OP and fragility fracture risks are those suffering from diseases associated with secondary OP, such as chronic inflammatory arthropathies, inflammatory bowel disease, intestinal malabsorption syndromes, chronic liver disease or advanced chronic kidney disease. In these cases the panel considers BMD reasonable in order to establish prevention measures and appropriate treatment for each individual patient.Trabecular Bone ScoreThe Trabecular Bone Score (TBS) is an analysis of the bone texture obtained from the DXA which evaluates parameters related to the bone micro architecture of the lumbar spine and has good correlation with computerised tomography.<a class="elsevierStyleCrossRefs" href="#bib1185">38,39</a> Low TBS values are associated with an increased risk of primary osteoporotic fracture, regardless of BMD.<a class="elsevierStyleCrossRef" href="#bib1185">38</a> The combination of TBS and lumbar BMD increases the reduction of the risk of developing fractures.<a class="elsevierStyleCrossRef" href="#bib1190">39</a> Furthermore, the introduction of the TBS in the FRAX® algorithm enables a better prediction of the development of future fractures.<a class="elsevierStyleCrossRefs" href="#bib1185">38,40,41</a> As a result, according to studies, the TBS could be an additional tool for the evaluation of fracture risk in patients with OP<a class="elsevierStyleCrossRefs" href="#bib1185">38–40</a> and in some causes of secondary OP (diabetes, hyperparathyroidism, glucocorticoids). However, its usefulness in the monitorisation of the therapeutic response has not yet been established.<a class="elsevierStyleCrossRef" href="#bib1185">38</a>To sum up, the panel of experts consider that although TBS could have several advantages in the evaluation of fracture risk, further studies are required to recommend its use in clinical practice.AnalysisRecommendation:It is recommend that a basic analytical study be performed to rule out secondary causes of osteoporosis (RR: √; AL: 100%).Basic laboratory tests to identify secondary OPs and make the differential diagnosis with other bone disease include<a class="elsevierStyleCrossRefs" href="#bib1145">30,42,43</a>: haemogram, serum calcium and phosphate tests, alkaline phosphatase, test, proteingram, albumin, creatinine, liver function tests, calciuria and 25-hydroxy vitamin D tests.Different scientific societies<a class="elsevierStyleCrossRefs" href="#bib1145">30,42,43</a> have produced documents with the following recommendations:<ul class="elsevierStyleList" id="lis0020"><li class="elsevierStyleListItem" id="lsti0075">•Additional tests will be carried out if there is suspicion of an associated condition:<ul class="elsevierStyleList" id="lis0025"><li class="elsevierStyleListItem" id="lsti0080">1.PTH (primary or secondary hyperparathyroidism).</li><li class="elsevierStyleListItem" id="lsti0085">2.TSH (hyperthyroidism).</li><li class="elsevierStyleListItem" id="lsti0090">3.Immunoelectrophoresis (myeloma).</li><li class="elsevierStyleListItem" id="lsti0095">4.Antitransglutaminase antibodies (celiac disease).</li><li class="elsevierStyleListItem" id="lsti0100">5.Urinary cortisol (Cushing's).</li><li class="elsevierStyleListItem" id="lsti0105">6.Serum tryptase (mastocytosis).</li><li class="elsevierStyleListItem" id="lsti0110">7.Sexual hormone study (young people).</li><li class="elsevierStyleListItem" id="lsti0115">8.Genetic study (imperfect osteogenesis, hypophosphatase and others).</li></ul></li></ul>Bone turnover markersRecommendation:The routine use of bone turnover markers has not been established. However, they could be considered in initial assessment and in follow-up of patients with osteoporosis (RR: B; AL: 89%).The reductions of the greatest magnitude in markers of bone turnover (MBT) are significantly associated to more marked reductions in the non vertebral fracture risk,<a class="elsevierStyleCrossRef" href="#bib1215">44</a> and the initial changes in a formation marker predict the efficacy of the bisphosphonates (BP) in the reduction of vertebral fracture risk.<a class="elsevierStyleCrossRef" href="#bib1220">45</a> However, there is not sufficient evidence to conclude that MBT are able to identify a reduction in risk fracture unequivocally.<a class="elsevierStyleCrossRef" href="#bib1225">46</a>The majority of GPC recommend the consideration of the use of MBT in the initial evaluation and in follow-up, as an additional test. In the initial evaluation, the high levels may predict a faster loss of bone mass and a higher risk of fracture. But their main indication is in follow-up, since they can contribute to assessing treatment adherence and efficacy, and also contribute to monitoring the duration of therapeutic holidays.<a class="elsevierStyleCrossRefs" href="#bib1145">30,42,43,47</a> The groups of international experts conclude that further research studies are required prior to making a recommendation based on the evidence.<a class="elsevierStyleCrossRef" href="#bib1210">43</a> To conclude, although the use of bone turnover markers has not been established as a routine, the panel of experts suggest that they could provide additional information in the initial evaluation and in the patient follow-up with OP.The two main serum references of MBT which are recommended to use by the IOF and the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) are the precollagen type I N-terminal propeptide (PINP), bone turnover marker and the Carboxyl-terminal telopeptide of type I collagen (CTX), a reabsorption marker.<a class="elsevierStyleCrossRef" href="#bib1235">48</a>Vertebral fracture screeningRecommendation:It is recommended that the presence of vertebral fractures be assessed in the patient with a high fracture risk or with osteoporosis, when kyphosis or significant loss of height has presented and when there is back pain or low back pain of recent onset (RR: D; AL: 100%).Chest and lumbar spine X-rays (focused on T7 and L3, respectively) are the method of choice for diagnosis of a vertebral fracture. A side projection is usually sufficient, thus minimising the radiation the patient receives.<a class="elsevierStyleCrossRef" href="#bib1240">49</a> These are useful in the initial evaluation of all patients diagnosed with OP when there is a significant loss of height or a change in relevant statics (especially thoracic kyphosis) and dorsolumbar pain of recent onset with or without a history of trauma<a class="elsevierStyleCrossRef" href="#bib1245">50</a> in a patient with a risk of OP or fracture. Height loss which is significantly associated with the presence of vertebral fractures is not defined, varying between 2cm compared with measurement in previous years to 4cm of historic loss since youth.<a class="elsevierStyleCrossRefs" href="#bib1145">30,51</a> The presence of a vertebral fracture, the number of them and their degree of severity are highly relevant indicators of the risk of new vertebral fractures, even those of the hip.<a class="elsevierStyleCrossRef" href="#bib1255">52</a>The panel of experts has thus considered that the presence of vertebral fractures should be assessed in the evaluation of the patient with OP or with a high risk of fracture when kyphosis or significant loss of height is present and there are clinical features of vertebral fracture. Some DXA teams also use the Vertebral Fracture Assessment (VFA) to assess fractures.TreatmentNon pharmacological therapiesRecommendation:Included in the prevention of primary and secondary osteoporosis and fractures is the recommendation for a healthy lifestyle, consisting of a balanced diet and regular physical exercise, not smoking, limiting alcohol consumption and using preventative measures against falls (RR: √; AL: 100%).Several studies have concluded that the first step to the prevention of OP and the avoidance of fractures is to maintain healthy life habits.<a class="elsevierStyleCrossRefs" href="#bib1260">53–57</a> Evidence suggests that exercise has a modest effect on reducing fractures and preventing falls.<a class="elsevierStyleCrossRef" href="#bib1280">57</a><a class="elsevierStyleCrossRef" href="#tbl0025">Table 3</a> contains a summary of the most important measures to be taken into consideration.<elsevierMultimedia ident="tbl0025"></elsevierMultimedia>Studies show that the adoption of fall prevention measures, in which exercise programmes and actions on environmental safety and minimisation of the use of drugs such as hypnotics, diuretics, antihypertensives and others which impair balance, also contribute both to primary and secondary fragility fracture prevention.<a class="elsevierStyleCrossRefs" href="#bib1280">57,58</a>In contrast, exercises which require great effort or are abrupt and those which involve repeated flexion or twisting of the trunk and abdominals are ill-advised.Regarding specific measures for the patient who has kyphosis, studies have proven the effectiveness of exercise, and training in muscular strength and balance.<a class="elsevierStyleCrossRef" href="#bib1290">59</a>The effectiveness of hip protectors in the prevention of fractures is inconclusive, and adherence to their use is very low.<a class="elsevierStyleCrossRef" href="#bib1295">60</a> Finally, vibratory platforms have not demonstrated any consistent efficacy.<a class="elsevierStyleCrossRef" href="#bib1300">61</a>Calcium and vitamin DRecommendation:It is recommended that a daily intake of calcium between 1000 and 1200mg be taken and that it should mainly originate from a regular diet (RR: D; AL: 100%).Recommendation:In the following cases a daily intake of 800UI of vitamin D is recommended (RR: D; GA: 100%):<ul class="elsevierStyleList" id="lis0030"><li class="elsevierStyleListItem" id="lsti0120">1.Patients with osteoporosis.</li><li class="elsevierStyleListItem" id="lsti0125">2.People over 65 years of age with fracture risk.</li><li class="elsevierStyleListItem" id="lsti0130">3.People with a vitamin D deficit.</li><li class="elsevierStyleListItem" id="lsti0135">4.People with limited exposure to the sun.</li><li class="elsevierStyleListItem" id="lsti0140">5.People with an insufficient calcium intake (under 700–800mg daily).</li></ul>Studies coincide in the need to ensure an adequate provision of calcium as an essential feature in any OP treatment programme.<a class="elsevierStyleCrossRef" href="#bib1230">47</a> Thus patients in pharmacological treatment for OP must use calcium and vitamin D supplements because practically all clinical trials which have demonstrated the efficacy of the antiosteoporotic drugs routinely include calcium supplements and cholecalciferol (vitamin D3). When the calcium provided in the diet is insufficient, it is recommended that calcium and vitamin D supplements be taken. In postmenopausal women with OP the international expert groups advise an intake of 800–1.200mg/of calcium per day and 800UI/of vitamin D per day.<a class="elsevierStyleCrossRefs" href="#bib1305">62,63</a>In primary prevention a daily intake of calcium of 1000–1200mg for women >50 years of age and men >70 years of age is advised, preferably in the diet, and 1000mg/of calcium per day in women <50 years of age and men aged between 51 and 70.Some foods are rich in calcium, such as milk products (milk, cheese, and yoghurt) tinned oily fish, beans and almonds. A list of foods and an online calculator are available in the IOF website.<a class="elsevierStyleCrossRefs" href="#bib1315">64,65</a> if supplements are used, the experts advise bearing in mind the optimum dose for calcium absorption which is situated in 500mg of calcium, and if larger doses are administered they should be spread over time.<a class="elsevierStyleCrossRef" href="#bib1325">66</a>With regard to the possible side effects of calcium supplements, constipation and dyspeptic upsets are the most notable. An increased risk of nephrolithiasis was demonstrated (RR 1.17) in the Women's Health Initiative<a class="elsevierStyleCrossRef" href="#bib1330">67</a> study, attributed to a diet rich in calcium of the women studied. However, a systematic review concluded that the calcium supplements in OP treatment, alone or in combination with other types of treatment, did not significantly increase the risk of nephrolithiasis or renal colic.<a class="elsevierStyleCrossRef" href="#bib1335">68</a> Controversy exists regarding the possible increased cardiovascular risk associated with calcium supplements, particularly if the recommended maximum dose is exceeded. The available evidence suggests that a total daily intake of calcium (obtained by adding up dietary intake plus supplements) under 2000mg did not increase cardiovascular risk.<a class="elsevierStyleCrossRefs" href="#bib1340">69,70</a>Regarding vitamin D, in OP patients, the conclusion reached by the experts is to maintain minimum serum concentrations of 25-hydroxy cholecalciferol (calcidiol) of 30ng/ml. They therefore recommend measuring the calcidiol levels in patients with a risk of vitamin D deficiency and in patients with OP. Given the essential role of sunlight as a source of vitamin D, they advise an exposure to the sun of 10–15min per day.<a class="elsevierStyleCrossRefs" href="#bib1305">62,63</a> When necessary; they advise vitamin D supplements with a dose between 800 and 2000UI/day, depending on baseline levels. In patients with hepatopathies, malabsorption syndromes, treatment with anticonvulsives or other situations where the vitamin 25D hydroxylation may be compromised, administration of the metabolite calcidiol is recommended.Current scientific evidence enables us to state that neither the increase of dietary calcium nor the isolated intake of calcium supplements is able to protect against the presence of fractures.<a class="elsevierStyleCrossRefs" href="#bib1350">71,72</a> Vitamin D administered as a monotherapy is not effective in reducing fragility fractures either, in non institutionalised elderly people.<a class="elsevierStyleCrossRefs" href="#bib1355">72,73</a> Calcium and vitamin D supplements have been show to be effective in the population >65 years of age who reside in care homes, reducing the risk of non vertebral fracture and marginally of hip fracture.<a class="elsevierStyleCrossRefs" href="#bib1355">72,74</a> This effect depends to a large extent on the vitamin D dose (≥800UI daily) and is more obvious at a greater age and with lower vitamin D levels.<a class="elsevierStyleCrossRef" href="#bib1355">72</a> Calcium and vitamin D supplements do not reduce the risk of vertebral fracture.<a class="elsevierStyleCrossRef" href="#bib1355">72</a>The efficacy of calcium and vitamin D supplements in the non institutionalised population >65 years of age (residents in the community) is questionable, as evidenced by the high number required to treat (NNT) to prevent fracture in this low risk population group<a class="elsevierStyleCrossRef" href="#bib1365">74</a> and the results of a recent meta-analysis.<a class="elsevierStyleCrossRef" href="#bib1370">75</a>There are contradictory data on the efficacy of vitamin D in the prevention of falls. Some results indicate that vitamin supplements, with and without calcium, would be effective in the prevention of falls,<a class="elsevierStyleCrossRef" href="#bib1375">76</a> and especially in the elderly with vitamin D deficit.<a class="elsevierStyleCrossRef" href="#bib1380">77</a> Other studies do not show this beneficial effect of vitamin D,<a class="elsevierStyleCrossRef" href="#bib1385">78</a> and even the administration of annual high doses could increase the risk of falls.<a class="elsevierStyleCrossRef" href="#bib1390">79</a>Treatment to prevent fracturesRecommendation:It is recommended that pharmacological treatment be initiated to reduce the Risk of osteoporotic fracture in the following situations (RR: √):<ul class="elsevierStyleList" id="lis0035"><li class="elsevierStyleListItem" id="lsti0145">1.Fragility fracture of vertebra or hip in patients >50 years of age (AL: 100%).</li><li class="elsevierStyleListItem" id="lsti0150">2.Other fragility fractures in patients >50 years of age and with low bone mass (T-score <−1 S) (AL: 89%).</li><li class="elsevierStyleListItem" id="lsti0155">3.OP defined by T-score ≤−2.5 SD in spine, femoral neck or total hip, always evaluating age, BMD figures and other risk factors (AL: 100%).</li><li class="elsevierStyleListItem" id="lsti0160">4.Patients with a high hip fracture risk according to FRAX®with BMD ≥3% (AL: 100%).</li><li class="elsevierStyleListItem" id="lsti0165">5.Males in androgen deprivation treatment and T-score ≤−2.5 SD (AL: 100%).</li><li class="elsevierStyleListItem" id="lsti0170">6.Women in treatment with aromatase inhibitors and T-score ≤−2 or with a T-score <−1.5 SD and an additional risk factor, or with ≥2 risk factors without BMD (AL: 100%).</li><li class="elsevierStyleListItem" id="lsti0175">7.Patients in treatment with glucocorticoids and: (a) initial dose ≥30mg/day of prednisone; (b) postmenopausal women and men >50 years of age with a dose of ≥5 mg/day and previous fragility fracture or T-score ≤−1.5 SD or high risk of fracture: FRAX®for hip ≥3% or for primary fracture ≥10% without BMD or ≥7.5% with BMD (AL: 78%).</li></ul>The drugs used for the treatment of OP have been shown to be more effective in patients with a high risk of fracture and in those with an existing fracture or with a T-score ≤−2.5 SD.<a class="elsevierStyleCrossRef" href="#bib1395">80</a>The NOF recommendations and those of other expert groups support the use of FRAX® in selecting candidates for treatment, including cases without OP using DXA.<a class="elsevierStyleCrossRefs" href="#bib1145">30,80</a>The panel thus considers that treatment is indicated in patients with fragility fracture, OP from DXA T-score ≤−2.5 SD, high fracture risk (FRAX® for hip fracture with BMD ≥3%)<a class="elsevierStyleCrossRefs" href="#bib1110">23,34</a> and in sub-groups of patients who take glucocorticoids, aromatase inhibitors<a class="elsevierStyleCrossRef" href="#bib1170">35</a> or antiandrogens.<a class="elsevierStyleCrossRef" href="#bib1180">37</a> The specific circumstances where osteoporotic antifracture treatment should be assessed is commented upon in detail in other sections.Regarding patients with fragility fractures, the NOF recommends treating all hip and vertebra fractures, whilst the other fractures would be treated depending on the results of the DXA and the risk of new fractures calculated using the FRAX®.<a class="elsevierStyleCrossRef" href="#bib1145">30</a>Regarding the evaluation of treatment based on the DXA outcome with a T-score ≤−2.5 SD, the panel wishes to highlight that in these cases clinical risk factors and the FRAX® should also be considered when decision are to be taken.Prophylaxis and treatment of OP induced by glucocorticoids are dealt with in a separate section.Several international guidelines, including those on oncology, advise that treatment be indicated for OP in women who receive aromatase inhibitors and have a T-score below or equal to −2 SD or with a T-score <−1.5 SD with an additional risk factor, or with ≥2 risk factors without BMD.<a class="elsevierStyleCrossRef" href="#bib1170">35</a> For men in androgen deprivation therapy, the IOF fixes the threshold for treating OP in a T-score of −2.5 SD or a raised fracture risk by FRAX®<a class="elsevierStyleCrossRef" href="#bib1180">37</a> (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).<elsevierMultimedia ident="fig0005"></elsevierMultimedia>Antifracture treatment choiceRecommendation:When selecting treatment, among other factors, it is recommended to take the following into consideration (RR: √; AL: 100%):<ul class="elsevierStyleList" id="lis0040"><li class="elsevierStyleListItem" id="lsti0180">1.The efficacy and safety of the drugs.</li><li class="elsevierStyleListItem" id="lsti0185">2.Cost-effectiveness ratio.</li><li class="elsevierStyleListItem" id="lsti0190">3.The value of the BMD.</li><li class="elsevierStyleListItem" id="lsti0195">4.The presence of fractures, particularly vertebral or multiple fractures due to fragility.</li><li class="elsevierStyleListItem" id="lsti0200">5.Treatments prior to this and adherence to them.</li><li class="elsevierStyleListItem" id="lsti0205">6.Age.</li><li class="elsevierStyleListItem" id="lsti0210">7.Comorbidities and polymedication.</li><li class="elsevierStyleListItem" id="lsti0215">8.Limitations for oral administration.</li></ul>The final aim of OP treatment is the prevention of fractures. <a class="elsevierStyleCrossRef" href="#tbl0025">Table 3</a> contains the efficacy in primary and secondary prevention of vertebral and non vertebral fractures of the drugs used in Spain.<a class="elsevierStyleCrossRefs" href="#bib1400">81–94</a>In the main studies conducted with drugs in patients who only had osteopenia without prevalent fracture (primary prevention) no fracture reduction occurred in primary outcome.In primary fracture prevention in patients with OP, the drugs which demonstrated a reduction of vertebral fracture were: alendronic acid, zoledronic acid, raloxifene, bazedoxifene and denosumab, whilst denosumab also reduced non vertebral fracture and hip fracture in this group.In patients with OP and vertebral fracture, alendronic acid, risedronic acid and zoledronic acid reduced new vertebral, non vertebral and hip fractures, whilst teriparatide reduced vertebral and non vertebral fractures and denosumab reduced vertebral fractures. For their part, ibandronic acid, raloxifene and bazedoxifene reduced vertebral fractures in patients with previous fracutre.<a class="elsevierStyleCrossRefs" href="#bib1400">81–94</a> With regard to forearm fractures, alendronic acid demonstrated a significant reduction of new wrist fractures in meta-analysis in patients with previous vertebral fracture.<a class="elsevierStyleCrossRef" href="#bib1400">81</a><a class="elsevierStyleCrossRefs" href="#tbl0030">Tables 4–7</a> contain details of the risk reduction for different fractures in the published studies.<a class="elsevierStyleCrossRefs" href="#bib1410">83–94</a><elsevierMultimedia ident="tbl0030"></elsevierMultimedia><elsevierMultimedia ident="tbl0035"></elsevierMultimedia><elsevierMultimedia ident="tbl0040"></elsevierMultimedia><elsevierMultimedia ident="tbl0045"></elsevierMultimedia>In patients with at least two moderate vertebral fractures or at least one severe fracture teriparatide was significantly more effective than risedronic acid for reducing new morphometric and clinical vertebral fractures after 24 months of treatment. There were no significant differences in the rate of new non vertebral fractures.<a class="elsevierStyleCrossRef" href="#bib1470">95</a>Strontium renalate has not been included in these recommendations because its production has been suspended, nor calcitonin, because of the limitation its technical record has in treatment indication and duration. However, therapy with oestrogens reduces vertebral and hip fractures, but is currently not used due to its poor risk/benefit profile and because safer treatments exist.The following aspects have to be taken into consideration when integrating trial outcomes into clinical practice: (1) the patient profile included is a postmenopausal woman with a high baseline risk due to age and the presence of previous fractures; (2) the populations of the trials are different to one another, and therefore may not be directly compared; (3) the studies were conducted with calcium and/or vitamin D supplements and (4) real treatment adherence is lower than that reported in the trials. Moreover, treatment should be individualised according to the circumstances of each patient.Another aspect to take into account is the cost/effectiveness ratio of treatment. The studies undertaken in other countries fix the threshold of FRAX® for primary fracture, so that the cost-effectiveness of the treatment is 8.8% (Portugal),<a class="elsevierStyleCrossRef" href="#bib1475">96</a> 13.8% (Switzerland)<a class="elsevierStyleCrossRef" href="#bib1480">97</a> and 10%–15% (Greece).<a class="elsevierStyleCrossRef" href="#bib1485">98</a> For estimation the cost of alendronic acid was considered (Portugal and Switzerland) and the average cost of treatment for OP (Greece). When drugs other than alendronic acid were considered, the FRAX® threshold for cost effectiveness was higher.<a class="elsevierStyleCrossRefs" href="#bib1475">96–98</a> Despite no cost-effectiveness studies existing for Spain based on fracture risk, the panel of experts advised taking into account BP as first line option in OP treatment.The panel of experts therefore consider that when choosing treatment to prevent fractures the efficacy and safety of the drugs, cost-effectiveness ratio, BMD figures, and presence of previous features (location, number and time passed since fracture) and oral administration route limitations should be contemplated. Other factors which also were to be taken into account were previous treatments and adherence to them, co morbidities and patient preferences. Thus, in patients with several fractures, oral intolerance, dementia, malabsorption and poor adherence, parenteral therapy could be considered.Sequential and combined therapyThe risk of long-term complications in OP treatments<a class="elsevierStyleCrossRefs" href="#bib1490">99–101</a> and the increase in the risk of fracture after their suspension<a class="elsevierStyleCrossRefs" href="#bib1505">102,103</a> often obliges physicians to put forward a sequential treatment strategy.Although there are currently no outcomes on fracture reduction with sequential treatment,<a class="elsevierStyleCrossRefs" href="#bib1515">104,105</a> the bone forming sequence (teriparatide) followed by antiresorptive sequence (denosumab or BP)<a class="elsevierStyleCrossRefs" href="#bib1515">104–106</a> is the most effective in terms of gaining BMD. Teriparatide followed by denosumab appears to be more effective than teriparatide followed by BP.<a class="elsevierStyleCrossRef" href="#bib1530">107</a>The administration of teriparatide after an antiresorptive drug is also effective, although its anabolic effect may slow down (less change in bone markers and lower increase of BMD),<a class="elsevierStyleCrossRef" href="#bib1535">108</a> and if administered after denosumab it has been described as a loss of initial BMD in the hip.<a class="elsevierStyleCrossRef" href="#bib1525">106</a> Sequential treatment with romosozumab followed by an antiresorptive drug is dealt with in the section relating to new treatments.Little information exists on the use of one antiresorptive drug followed by another, especially if the first was administered for years. A review of 11 prospective studies of patients previously treated with alendronic acid or risedronic acid showed that the change to ranelate from strontium or denosumab achieved an additional increase in BMD.<a class="elsevierStyleCrossRef" href="#bib1540">109</a> However, no data were available on fracture reduction either.<a class="elsevierStyleCrossRef" href="#bib1540">109</a> In one study denosumab showed increases in BMD in patients who had been treated with zoledronic acid.<a class="elsevierStyleCrossRef" href="#bib1545">110</a>There are studies which show greater efficacy in combined therapy (bone formation and antiresorptive) compared with monotherapy. The combination of zoledronic acid and teriparatide has been associated with a higher increase in femoral BMD one year after treatment compared with teriparatide in monotherapy.<a class="elsevierStyleCrossRefs" href="#bib1515">104,111</a> The combination of denosumab and teriparatide has been associated with a greater increase in lumbar spine and proximal femur BMD, compared with both drugs in monotherapy.<a class="elsevierStyleCrossRef" href="#bib1555">112</a> Notwithstanding, there is no evidence of reduction of fractures with these combinations. After a review of the literature, the panel concluded that combined (bone formation and antiresorptive) treatment did not appear to be an option to recommend in general, although its use could be justified in highly selected serious cases of OP.Treatment durationOP is a chronic disease, and treatment must therefore be maintained indefinitely or at least for several years. However, there is no recommended maximum treatment for each drug used.<a class="elsevierStyleCrossRefs" href="#bib1205">42,100</a>The antiresorptive drugs (selective oestrogen receptor modulators, SERM, BP and denosumab) generally reduce fracture risk from 12 to 18months<a class="elsevierStyleCrossRefs" href="#bib1435">88,91,113</a> and have no maximum approved duration.In the case of BP, its efficacy, in terms of BMD and fracture risk reduction is maintained for at least 3 years of treatment.<a class="elsevierStyleCrossRefs" href="#bib1565">114,115</a> Some studies show that from the 4th or 5th year BMD slightly rises or remains stable and the risk of some complications increases so that after 5 years of treatment with oral BP or 3 years with zoledronic acid it is advisable to evaluate the risk/benefit of continuing with treatment.<a class="elsevierStyleCrossRef" href="#bib1575">116</a> The Groups of experts agrees in recommending maintaining treatment (up to 10 years for oral BP or up to 6 years for zoledronic acid) in patients with a high fracture risk (fractures prior or during treatment, age >75 years or T-score ≤−2.5 SD in femoral neck or total hip).<a class="elsevierStyleCrossRefs" href="#bib1205">42,100,117,118</a>Denosumab produces a progressive increase of BMD for at least 10 years of treatment, maintaining its ant fracture efficacy over time.<a class="elsevierStyleCrossRef" href="#bib1590">119</a> Although there is no consensus regarding the duration of this treatment, some authors indicate that it could be established according to a predefined objective (treat to target strategy), i.e. after reaching a certain BMD value.<a class="elsevierStyleCrossRef" href="#bib1595">120</a> however, they should not suspend treatment with denosumab without establishing other treatment for OP (see section “Suspension or discontinuation of treatment”).Although data exist on efficacy and safety of SERM (raloxifene and bazedoxifene) up to 8 years, maximum duration of the treatment is conditioned by the risk of complications such as thromboembolism, which is more frequent in patients over 70.<a class="elsevierStyleCrossRef" href="#bib1600">121</a>Regarding patients who receive glucocorticoids, aromatase inhibitors or androgen deprivation therapy, the panel of experts consider that antiresorptive treatment should be maintained at least whilst the patient receives the inductor drug of OP (see “Osteoporosis by glucocorticoids”).Teriparatide has been shown to reduce the risk of fracture after 6–12months of treatment initiation. However, to achieve maximum efficacy, both in trabecular and cortical bones, different groups of experts agree that it is recommendable to maintain it for 2 years, which is the maximum period approved.<a class="elsevierStyleCrossRefs" href="#bib1205">42,100,108</a>Treatment suspension or discontinuationRecommendation:It is recommended that fracture risk be reassessed after 5 years of treatment with oral bisphosphonates or after 3 years of treatment with zoledronic acid (RR: D; AL: 100%).Recommendation:When treatment with denosumab it suspended an alternative treatment for osteoporosis should be contemplated (RR: D; AL: 100%).Recommendation:In patients with high fracture risks like those with a previous fragility fracture, or with a T-score of proximal femur <−2.5 SD, it is not recommended to discontinue osteoporosis treatment (RR: D; AL: 89%).OP treatment implies that the patient will receive medication for years, although in some cases it is possible to have interruptions. The so-called “therapeutic holidays” are a temporary suspension of treatment with BP to reduce the presence of adverse effects, because they accumulate in the bone tissue and maintain their effect even years after having been suspended.<a class="elsevierStyleCrossRefs" href="#bib1570">115,122–124</a> This residual effect is not observed with other drugs such as SERM, denosumab or teriparatide.Although the decision to discontinue treatment with BP must be individualised, the consensus of experts advise reassessing treatment in patients with low fracture risk and who have not presented with incident fractures after 5 years of treatment with oral BP or 3 years with zoledronic acid.<a class="elsevierStyleCrossRef" href="#bib1495">100</a> The duration of this discontinuation is unknown and has been calculated to be between 2 and 3years, depending on the BP used.<a class="elsevierStyleCrossRefs" href="#bib1495">100,125</a> Although there is little evidence, the changes in BMD and bone turnover markers could help with decision-making.<a class="elsevierStyleCrossRef" href="#bib1495">100</a>The majority of international guidelines advise not to suspend treatment with BP in high fracture risk patients, like those with previous fragility fractures, a low T-score in hip or in those who present with a fragility fracture during treatment.<a class="elsevierStyleCrossRefs" href="#bib1495">100,126,127</a> Regarding the value of the BMD capable of predicting a high fracture risk on suspending treatment, the post hoc analysis of the FLEX and HORIZON studies state this as a femoral T-score <−2.5 SD.<a class="elsevierStyleCrossRefs" href="#bib1605">122,124</a> If treatment with BP is prolonged, it seems reasonable to reassess after 5 years of treatment with oral BP or 3 years with zoledronic acid.<a class="elsevierStyleCrossRefs" href="#bib1495">100,126</a>According to different scientific societies and groups of experts, the concept of treatment suspension should not be applied to other drugs such as denosumab, since its removal may lead to an increase in bone remodelling, with a decrease in BMD and an increase in fracture risk, including multiple fractures after its suspension.<a class="elsevierStyleCrossRefs" href="#bib1630">127–130</a> For this reason, they concluded that if it is decided to suspend treatment for any reason with denosumab, an alternative treatment should always be considered.<a class="elsevierStyleCrossRef" href="#bib1635">128</a> The panel of experts, despite little evidence regarding the consequences of suspension of denosumab and its alternative treatment efficacy, recommend that when treatment is suspended with denosumab an alternative OP treatment be sought.Follow-up, monitorisation and adherenceRecommendation:Periodical clinical evaluation for confirming compliance and efficacy of treatment, incidence of fractures and the possible presence of adverse effects is recommended (RR: √; AL: 100%).AdherenceLow OP treatment adherence is a frequent problem, after 12 months of treatment less than half of the patients stick to the therapy they were prescribed.<a class="elsevierStyleCrossRef" href="#bib1650">131</a> Low adherence is also associated with an increased fracture risk.<a class="elsevierStyleCrossRef" href="#bib1655">132</a>The efficacy of different measures has been studied to improve adherence, such as telephone calls or meetings with patients, but none of them appear to have been truly effective.<a class="elsevierStyleCrossRef" href="#bib1660">133</a> In a systematic review of 20 studies it was observed that the simplification of posology, electronic prescription and the intervention of the pharmacist improved adherence or persistence of OP treatment. Patient education has demonstrated its effectiveness in several studies, but not in all of them, whilst monitorisation and supervision had no significant impact on adherence.<a class="elsevierStyleCrossRef" href="#bib1665">134</a> However, the Fracture Liaison Service (FLS) units for secondary fracture prevention reported an adherence >70% at 1–2 years, which was related partly to the educational efforts made by the nurse.<a class="elsevierStyleCrossRefs" href="#bib1670">135,136</a>MBT could help with follow-up and adherence. The IOF and European Calcified Tissue Society (ECTS), in a workgroup for analysing the usefulness of the MBT in oral BP adherence, recommended measuring PINP and CTX at the beginning of treatment and after 3 months, to verify whether there was a greater reduction to the minimum significant change of the MBT.<a class="elsevierStyleCrossRef" href="#bib1680">137</a> The same workgroup considered a significant change to be a reduction that was higher than 38% for PINP and above 56% for CTX, whilst absence of change suggested the need for reassessment to identify problems with treatment, mainly low adherence.<a class="elsevierStyleCrossRef" href="#bib1680">137</a> In one meta-analysis of 6 studies which assessed the efficacy of the MBT to improve treatment adherence, compliance was a high average, and it was difficult to assess the repercussion of the act of informing of the outcomes of the MBT.<a class="elsevierStyleCrossRef" href="#bib1225">46</a> In the meta-analysis one study stood out where higher persistence was observed if the patient was informed of their response to treatment (HR for discontinuation 0.71; 95% CI: .53–.95), whilst informing of the poor response to the drug reduced it (HR for discontinuation 2.22; 95% CI: 1.27–3.89).<a class="elsevierStyleCrossRef" href="#bib1685">138</a> The reinforcement using the outcomes of the MBT thus had an influence on persistence, depending on the response of the MBT.MonitorisationOP treatment monitorisation includes the analytical determinations and the DXA, as well as asking the patient about new fractures. Several studies conclude that the bone remodelling markers could be useful for early monitoring of compliance and response to treatment,<a class="elsevierStyleCrossRef" href="#bib1690">139</a> but the panel of experts consider that they cannot recommend their systematic determination in patient follow-up. The panel recommends monitoring the response to treatment through central DXA, bearing in mind patient characteristics.There are no controlled, good quality studies on the frequency with which measurement of the BMD should be repeated during treatment.<a class="elsevierStyleCrossRef" href="#bib1695">140</a> Possible variation in BMD with current treatments is slow to occur and usually of little magnitude. Given the risk of DXA measurement error, international experts concluded that measurement should be made when the expected change is equal to or higher than the minimum significant difference.<a class="elsevierStyleCrossRef" href="#bib1155">32</a> For this reason, in general, it is not advised to repeat measurement of the BMD before 2–3 years.<a class="elsevierStyleCrossRefs" href="#bib1020">5,141</a> Other guidelines advise lengthening this time period to 3 years for zoledronic acidy and up to 5 years for oral BP.<a class="elsevierStyleCrossRefs" href="#bib1625">126,142,143</a> In situations of high fracture risk,<a class="elsevierStyleCrossRef" href="#bib1020">5</a> in treatment with high doses of glucocorticoids or when there is a suspicion of failure in therapy, such as when a new fracture occurs, the period for repeating DXA may be shortened.<a class="elsevierStyleCrossRef" href="#bib1715">144</a> The aim is to detect the patients who, despite treatment, suffer from a significant drop in BMD. It is also advised to carry out a DXA when planning temporary suspension of the drug for “therapeutic holidays”.<a class="elsevierStyleCrossRef" href="#bib1615">124</a> Although the greatest changes in BMD are detected in the lumbar spine, it is useful to also monitor the hip, as it is less dependent on artefacts impacted by degenerative changes.Several authors propose using a treat to target strategy in OP where the objectives would be to reach a certain value of the T-score (for example, T-score: −2.5 SD) or BMD. If this occurred, monitorisation of the BMD would enable the knowledge of whether the therapeutic aim had been reached. However, not all drugs lead to an improvement of BMD proportional to the reduction of fracture risk, and the real value of this strategy in clinical practice is also yet to be defined.<a class="elsevierStyleCrossRef" href="#bib1580">117</a>Determination of TBS provides information on the changes which treatment may produce on bone microarchitecture,<a class="elsevierStyleCrossRef" href="#bib1720">145</a> but insufficient data is available to recommend its use in clinical follow-up.Therapy failureThe definition of therapeutic failure in the treatment of OP is complex and there are no established criteria. Experts agree that it is advisable to ensure that treatment adherence is correct, confirm an adequate supply of calcium and vitamin D and rule out secondary OP causes. With regard to treatment failure, after one year of treatment with any antiosteoporotic drug, a group of international experts suggest the following criteria of assessment for treatment changes<a class="elsevierStyleCrossRef" href="#bib1715">144</a>:<ul class="elsevierStyleList" id="lis0045"><li class="elsevierStyleListItem" id="lsti0220">1.Two or more fragility fractures during treatment.</li><li class="elsevierStyleListItem" id="lsti0225">2.One fragility fracture together with one of the following factors:<ul class="elsevierStyleList" id="lis0050"><li class="elsevierStyleListItem" id="lsti0230">-Significant loss of BMD (>5% in lumbar spine or >4% in proximal femur).</li><li class="elsevierStyleListItem" id="lsti0235">-Absence of significant changes in the MBT (reduction of PINP or CTX >25% with antiresorptive treatment, or increase >25% with bone turnover treatment after 6 months).</li></ul></li><li class="elsevierStyleListItem" id="lsti0240">3.Absence of significant changes in the MBT together with a significant loss of BMD.</li></ul>Treatment safetyIn general the drugs approved for OP treatment are safe and present with good tolerability.<a class="elsevierStyleCrossRef" href="#bib1725">146</a> Oral BP may lead to a series of adverse digestive effects (pyrosis, dyspepsia, esophagitis, dysphagia or abdominal pain) and oral effects (conjuntivitis, anterior uveitis), of minor intensity in most cases, which disappear when the drug is withdrawn. After the first infusion of zoledronic acids symptoms of unclarified origin have been described characterised by fever, myalgias and bone pains and this occurs in between 20% and 30% of patients. In subsequent infusions the symptoms tend to disappear. This effect may occur rarely with oral BP.Treatment with BP does not increase cardiovascular risk. No association has been demonstrated between the development of auricular fibrillation and treatment with oral BP. In one study an increased risk of auricular fibrillation was observed with the use of intravenous zoledronic acid.<a class="elsevierStyleCrossRef" href="#bib1730">147</a> Isolated cases of cancer of the oesophagus have been published in patients on oral BP, but the most recent studies have not confirmed this relationship.<a class="elsevierStyleCrossRef" href="#bib1735">148</a> Osteomuscular pain, kidney damage and hepatotoxicity from BP are exceptional and will rarely lead to withdrawal of the drug.<a class="elsevierStyleCrossRef" href="#bib1740">149</a> Use of BP is not advised in patients with glomerular filtration rate <30ml/min, since there are no available studies that have demonstrated a reduction in fractures in these patients and on the contrary, they increase the risk of impairment of a reduced remodelling osteodystrophy.Denosumab, in the guideline approved for the treatment of OP, is a drug which is generally well tolerated. A higher rate of infections has been observed, and in particular cutaneous<a class="elsevierStyleCrossRef" href="#bib1435">88</a> and urinary,<a class="elsevierStyleCrossRef" href="#bib1745">150</a> but their overall rate is very low.<a class="elsevierStyleCrossRef" href="#bib1750">151</a> However, due to their structure, they are not eliminated by the kidney, which is an advantage for patients with kidney diseases where a higher risk of hypocalcaemia must be monitored. As with BP, denosumab should not be used when there is clinical suspicion or histomorphometric evidence of reduced remodelling osteodystrophy.Adverse reactions to teriparatide are generally not serious. Muscle pain, cramps and dizziness are frequent. Treatment with teriparatide may raise calcaemia and calciuria, and it is therefore advisable to determine the levels of calcium in the blood and urine prior to initiating treatment.In recent years complications have appeared which are associated with prolonged treatment with antiresorptives (BP and denosumab) and which have generated uncertainty about safety. The relative importance of these rare adverse effects (osteonecrosis of the jawbones and atypical femur fracture) in the treatment of OP is a highly controversial issue.The fear of patients in suffering these complications may be an impediment for adherence and therapeutic compliance, although the benefit–risk balance of maintaining treatment is highly favourable for high fracture risk patients. A brief analysis will now be made of both complications, based on the systematic reviews carried out to complete this document.Osteonecrosis of the jawbonesRecommendation:If any invasive dental procedures has been indicated to the OP patient (dental extraction or implant) it is recommended that antiresorptive treatment initiation be postponed until the surgical wound has completely healed (RR: D; AL: 100%).Recommendation:In patients treated with antiresorptives who are going to carry out a dental procedure it is not recommended that they discontinue treatment with BP or denosumab. If other additional osteonecrosis of the jawbone risks prevail or the surgical procedure is to be extensive, temporary suspension of the treatment with BP may be considered (RR: D; AL: 78%).Osteonecrosis of the jawbones has been associated with the prolonged use of BP or denosumab, although its rate in patients with OP is very low (between 1/10,000 and 1/100,000).<a class="elsevierStyleCrossRefs" href="#bib1755">152–154</a>According to the outcomes of a previous review, published in 2013, available evidence on BP is scarce and of low quality.<a class="elsevierStyleCrossRef" href="#bib1765">154</a> There is insufficient data to confirm that oral BP or intravenous BP used for OP treatment confers any significant risk of osteonecrosis of the jawbones. There have not been enough studies to assess the role of denosumab in the development of osteonecrosis of the jawbones (level of evidence 3).<a class="elsevierStyleCrossRefs" href="#bib1755">152,153</a> Several systemic factors such as previous treatment with BP or dental extractions are associated with the development of osteonecrosis of the jawbones in patients treated with denosumab (level of evidence 3).<a class="elsevierStyleCrossRef" href="#bib1760">153</a>Several medical associations have published recommendations to reduce the risk of this complication. In general, guidelines include correct dental hygiene in their proposals and dental check-up if poor dental health is observed. If any invasive dental procedures has been indicated (dental extraction or implant) it is recommended that treatment initiation be postponed until the surgical wound has completely healed.<a class="elsevierStyleCrossRef" href="#bib1770">155</a> The use of CTX marker thresholds have been suggested to assess the baseline risk of osteonecrosis of the jawbones. However, available evidence does not endorse its use.<a class="elsevierStyleCrossRef" href="#bib1775">156</a>There is some controversy regarding the which approach to take in patients who are already taking BP or denosumab. The majority of guidelines advise not to suspend antiresorptive treatment in non oncological patients. In 2011, the American Dental Association guide recognised that the risk of osteonecrosis of the jawbones was very low in patients with OP, and it was therefore not necessary to suspend an oral BP prior to a dental procedure.<a class="elsevierStyleCrossRef" href="#bib1780">157</a> However, and according to the recommendations made by the international panel of experts, in patients who have undergone extensive oral surgery and with associated risk factors (diabetes, periodontal disease, immunodeficiency, tobacco habit), clinical judgement may suggest temporal suspension of treatment.<a class="elsevierStyleCrossRef" href="#bib1770">155</a> In this situation, and given that withdrawal of denosumab leads to a bone remodelling and the risk of appearance of multiple vertebral fractures, the panel considers that treatment with denosumab should not be interrupted.During OP treatment, invasive dental procedures may be made only after careful consideration of their necessity. In the case of denosumab, and whenever possible, surgery must be avoided in periods close to drug administation.<a class="elsevierStyleCrossRef" href="#bib1785">158</a> In this situation a prolonged unnecessary suspension should be avoided, especially in patients treated with denosumab. Should a relevant adverse event occur such as osteonecrosis of the jawbones, and although no scientific evidence demonstrates withdrawal of the drug will help the process evolve, the same document considers it prudent to suspend treatment and assess drug indication with a different mechanism of action.<a class="elsevierStyleCrossRef" href="#bib1770">155</a>Atypical femur fractureRecommendation:In patients with high fracture risk and prolonged treatment with bisphosphonates (>5 years for orals or >3 years for intravenous) it is recommended not to suspend treatment, since the risk of atypical femur fracture is very low and the benefits of fracture reduction greatly outweigh the risk of atypical fracture (RR: D; AL: 100%).Atypical fracture of the femur is a potential complication from prolonged treatment with BP or denosumab, although real incidence is very low.According to the definition proposed by the American Society for Bone and Mineral Research (ASBMR),<a class="elsevierStyleCrossRef" href="#bib1790">159</a> the atypical fracture of the femur is located between the lesser trochanter and the suprachondylar crest and should present with a minimum of 4 out of the following 5 criteria: (1) minimum or absent trauma; (2) origin of the fracture in the external cortical and directed cross-sectionally or obliquely; (3) without comminution or, if this exists, it must be minimal; (4) periostic or endostic thickening of the external, localised cortical, and (5) involvement of the external side cortical (incomplete fracture) or both corticals (complete fracture). Minor criteria are not essential for diagnosis, but they increase it: (a) cortical thickness increased diffusely in femoral diaphysis; (b) pain in thighs or groin area, prior to fracture; (c) bilateral fracture of similar characteristics, and (d) delay in consolidation.Apart from prolonged treatment with antiresorptives, the atypical fracture of the femur has also been associated with several comorbidities or with taking medication such as proton pump inhibitors or glucocorticoids.According to the results of a previous 2011 review, the rate of atypical fracture of the femur was very low and it could not be confirmed that there was a significant increase in the risk of atypical fracture of the femur in patients with Op treated with BP. Since then several poor quality studies have been published which show that the rate of atypical fracture of the femur as very low. Two of the 3 published meta-analyses,<a class="elsevierStyleCrossRefs" href="#bib1795">160,161</a> based on randomised clinical trials (RCT), cohort, case and control studies, with a high degree of overlapping, demonstrated a significant increase in the risk of subtrochanteric or diaphysary fracture with the use of BP ranged between 1.70 and 1.99, although with a high level of heterogeneity. In a third meta-analysis which only explored alendronic acid,<a class="elsevierStyleCrossRef" href="#bib1805">162</a> the relative risk of atypical fracture of the femur with this drug was 3.23 (95% CI: .88–11.84), but the differences were not significant. When a stratified analysis was made with the studies to assess the effect of alendronic acid over 5 years, heterogeneity was insignificant. Using a model of fixed effects, the relative risk was 2.55 (95% CI: 2.26–2.88), concluding that the alendronic acid did not increase the risk of atypical fracture of the femur short-term, but it did in the long term (>5 years).<a class="elsevierStyleCrossRef" href="#bib1805">162</a>A recent systematic review<a class="elsevierStyleCrossRef" href="#bib1805">162</a> concluded that the rate of atypical fracture of the femur associated with BP was very low, but that the relative risk (RR) increased with prolonged use (especially if it was over 3 years). According to the authors, the benefits of BP in reduction of OP fractures greatly outweigh the risk of atypical femur fracture. A limiting feature highlighted was that almost all studies were retrospective and of variable duration (4–9 years), limiting the interpretation of long term exposure.Regarding the RCT,<a class="elsevierStyleCrossRefs" href="#bib1810">163,164</a> isolated cases have been reported on atypical femur fractures, but these studies present with relevant limitations, such as the short duration of the same, the non-inclusion of this outcome as a main variable or the losses in follow-up, which impede the obtainment of reliable outcomes. If we analyse observational studies,<a class="elsevierStyleCrossRefs" href="#bib1820">165,166</a> the incidence and absolute risk of atypical fracture of the femur in patients treated with BP have very low rates (between 10.8 and 19.1 per 100,000 patients per year).The rate of atypical femur fracture represents 0.3% of the total of femur fractures or 5% of the total of subtrochanteric/diaphyseal fractures. Women represent 80% of all diaphyseal fractures and 95% of the atypical fractures of the femur, with a relative risk which is higher in men. The outcome of recent review studies and meta-analyses suggest a favourable benefit/risk ratio to maintain treatment up until 10 years with antiresorptives.Regarding denosumab, the systematic review results on the risk of atypical femur fracture are very limited due to the scarcity of high quality studies. The studies included were one RCT,<a class="elsevierStyleCrossRef" href="#bib1730">147</a> two follow-up studies<a class="elsevierStyleCrossRefs" href="#bib1830">167,168</a> and one cohort study.<a class="elsevierStyleCrossRef" href="#bib1840">169</a>According to observational studies, long-term treatment with denosumab (between 7 and 10 years) is associated with a nil<a class="elsevierStyleCrossRef" href="#bib1835">168</a> or very low rate of atypical fracture of the femur (.8 per 10,000 patients per year).<a class="elsevierStyleCrossRef" href="#bib1830">167</a> A clinical trial of postmenopausal women with OP who had switched from BP to denosumab was unable to demonstrate that the rare cases of atypical fracture of the femur which appeared early on could be attributable to the use of denosumab, in contrast they appeared to be derived from prior use of BP.<a class="elsevierStyleCrossRef" href="#bib1795">160</a>Although cases of atypical femur fracture have been described in patients treated with denosumab, the panel of experts decided not to make a specific recommendation on the risk of atypical femur fracture with denosumab due to low evidence and the need for further studies with a higher number of cases and longer time period.To reduce the clinical impact of atypical femur fracture, in patients under prolonged treatment with BP or denosumab attention must be paid to the presence of pain in the thighs. In these cases it is recommended that X-rays be performed to detect stress fractures or cortical thickening and for early determination of atypical femur fracture. It may also be useful to use magnetic resonance or a bone scan to confirm diagnosis.Treatment of an atypical femur fracture is surgical. When this complication arises, studies conclude that antiresorptive treatment should be withdrawn, the pain treated, an adequate provision of calcium and vitamin D ensured and a drug with a different mechanism of action be indicated.<a class="elsevierStyleCrossRef" href="#bib1845">170</a> No control studies exist On the efficacy of teriparatide in patients who have suffered an atypical femur fracture. In a short series of cases, treatment with teriparatide increased the bone mass and the bone remodelling markers, but with no consistent effect on fracture consolidation.<a class="elsevierStyleCrossRef" href="#bib1845">170</a>Special situationsFragility fractureRecommendation:It is recommended that all patients’ ≥50 years of age with a recent fragility fracture be assessed systematically to prevent further fractures (RR: D; AL: 100%).Patients with fragility fracture have a significant increase in the risk of further fractures. However, it is normal that fewer than 25% of them start treatment for OP after a fracture.<a class="elsevierStyleCrossRef" href="#bib1015">4</a> The term “imminent fracture risk” has recently been introduced to refer to patients with recent fractures, fragile elderly people with frequent falls and fracture patients who have started treatment with high doses of glucocorticoids.<a class="elsevierStyleCrossRef" href="#bib1055">12</a>In keeping with the EULAR<a class="elsevierStyleCrossRef" href="#bib1850">171</a> recommendations the panel of experts suggested that all patients with recent osteoporotic fracture aged ≥50 years of age should be systematically assessed to prevent new fractures.The FLS model, or Fracture Unit appears to be the most effective<a class="elsevierStyleCrossRef" href="#bib1855">172</a> in terms of evaluation and treatment initiation. It is also cost-effective<a class="elsevierStyleCrossRef" href="#bib1860">173</a> and positive experiences have been had with it in Spain.<a class="elsevierStyleCrossRef" href="#bib1675">136</a> The central element of a Fracture Unit is the coordinator (in Spain this is usually a medical bone metabolism expert), who works in close collaboration with a specialised nurse. The keys to success in the Fracture Unit are: (a) identification of all cases, usually from a list of emergencies and of hospitalised patients; (b) study of the patients, including determination of risk factors, DXA and analysis; (c) the advice of the nurse on non pharmacological measures and adherence to medication; (d) early initiation of antifracture treatment and (e) the drawing up of a report with precise indications for the primary care physician.In patients with fragility fracture the panel of experts concludes that it would be useful to assess fracture risk factors and falls and identify secondary OP. They advise the carrying out of DXA and assessment of the presence of vertebral fractures.Vertebral fractureRecommendation:The treatment of choice for an acute vertebral fracture is rest, rapidly scaled analgesics to control pain, and if necessary the use of a brace (RR: √; AL: 100%).Acute vertebral fracture may lead to serious pain and disability, lasting for several months.<a class="elsevierStyleCrossRef" href="#bib1865">174</a> General measures that have been shown to be useful and shorten the recovery period are bedrest (for 4 days or less) and rapidly scaled analgesics (including the use of powerful opiates when necessary).<a class="elsevierStyleCrossRef" href="#bib1870">175</a>Ortheses (rigid or semi-rigid brace) are useful for acute episode in combination with analgesic treatment, as they help to immobilise the fracture, reduce load and improve spinal alignment in patients who can tolerate them. The type of orthesis will depend on fracture location. Prolonged use is not advisable. It has not been demonstrated that the rate of new fractures will decrease.<a class="elsevierStyleCrossRef" href="#bib1875">176</a>In patients with persistent and highly intense pain (visual analogue scale [VAS] ≥7), after 4–6 weeks of treatment as described above, some studies concluded that facet infiltrations could be considered or radiofrequency ablation of the lumbar medial branch,<a class="elsevierStyleCrossRef" href="#bib1880">177</a> before prescribing a vertebroplasty or kyphoplasty. According to other studies, in the sub-acute and chronic phase it would be beneficial to have physical therapy using heat applied techniques, ultrasound or hydrotherapy and a progressive initiation of an exercise programme to strengthen the paravertebral and thoracoabdominal muscles.<a class="elsevierStyleCrossRef" href="#bib1885">178</a> Weight-bearing exercises and balance training prevent falls and fractures and improve the patient's quality of life.<a class="elsevierStyleCrossRefs" href="#bib1290">59,176</a>Vertebroplasty and kyphoplastyIn which cases would vertebroplasty and kyphoplasty be indicated?Recommendation:Vertebroplasty and kyphoplasty are recommended for the treatment of vertebral fracture only in cases of serious refractory pain on a WHO analgesic scale, including opiates (RR: D; AL: 100%).Systematic reviews of the clinical efficacy of vertebroplasty in patients with fractures due to OP, with pain which is refractory to analgesic treatment, conclude that in open trials vertebroplasty has better results than an optimum analgesic treatment in improving quality of life and reducing pain and disability.<a class="elsevierStyleCrossRefs" href="#bib1890">179,180</a> However, in double blind trials there is no evidence that vertebroplasty is superior to placebo with local anaesthesia. Also, after a month, the average pain, according to the VAS, was 5 points in the placebo group and 4.3 points in the vertebroplasty group, with an absolute reduction in pain of 7% and a relative reduction of 10%.<a class="elsevierStyleCrossRef" href="#bib1890">179</a> Evidence of its clinical efficacy is not consistent. The complications associated with the procedure are rare, but may be serious. Notwithstanding, it cannot be determined with certainty whether vertebroplasty leads to an increased risk of new fractures in adjacent vertebra.<a class="elsevierStyleCrossRefs" href="#bib1890">179,180</a>Systematic reviews of the clinical efficacy of kyphoplasty conclude that in open studies it has better outcomes than conservative treatment in improving quality of life and reducing pain and disability, but the evidence of its clinical efficacy is not consistent as there are no available double blind studies to compare with placebo.<a class="elsevierStyleCrossRefs" href="#bib1890">179,181</a>Reduction in pain associated with kyphoplasty analysed through VAS, compared with conservative treatment, was −1.82 after 30 days, −1.45 after 3 months and −1.48 after 6 months, but −.84 and −.69 after 12 and 24 months, respectively.<a class="elsevierStyleCrossRef" href="#bib1900">181</a> The authors conclude that vertebroplasty and kyphoplasty could improve quality of life and reduce pain in vertebral fractures refractory to analgesic treatment, with a doubtful increase in the rate of new fractures in the adjacent vertebra. There is therefore not sufficient evidence for their recommendation in standard clinical practice.Osteoporosis from glucocorticoidsRecommendation:In patients who receive or who are going to receive treatment with glucocorticoids fracture risk must be assessed and the initiation of treatment for osteoporosis as soon as possible (RR: D; AL: 100%) (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>).<elsevierMultimedia ident="fig0010"></elsevierMultimedia>Recommendation:It is recommended that pharmacological treatment be initiated to prevent OP in patients who are going to receive glucocorticoids for over 3 months in the following cases (RR: D):<ul class="elsevierStyleList" id="lis0055"><li class="elsevierStyleListItem" id="lsti0245">1.Patients with an initial dose ≥30 mg/day of prednisone. In these cases it is recommended that treatment be imitated for the OP immediately (AL: 100%).</li><li class="elsevierStyleListItem" id="lsti0250">2.Postmenopausal women and men >50 years of age with doses of prednisone ≥5mg/day who also present with some of the following conditions:<ul class="elsevierStyleList" id="lis0060"><li class="elsevierStyleListItem" id="lsti0255">a)Previous fragility fracture (AL: 100%).</li><li class="elsevierStyleListItem" id="lsti0260">b)Low BMD (T-score ≤−1.5 SD in spine or hip) (AL: 89%).</li><li class="elsevierStyleListItem" id="lsti0265">c)High fracture risk: FRAX®for hip ≥3% or for primary fracture ≥10% without BMD or ≥7.5% with BMD (AL: 78%).</li></ul></li><li class="elsevierStyleListItem" id="lsti0270">3.Premenopausal women and men <50 years of age and dose ≥7.5mg/day of prednisone who also present with some of the following conditions:<ul class="elsevierStyleList" id="lis0065"><li class="elsevierStyleListItem" id="lsti0275">a)Previous fragility fracture (AL: 100%).</li><li class="elsevierStyleListItem" id="lsti0280">b)Low BMD (Z-score ≤−3 SD) (AL: 78%).</li></ul></li></ul>OP induced by glucocorticoids is the most frequent cause of secondary OP, and is associated with the presence of fractures in up to 30%–50% of cases.<a class="elsevierStyleCrossRef" href="#bib1905">182</a> The risk of fracture depends on factors such as age, prior BMD, daily accumulated dose of glucocorticoids and baseline disease. The loss of BMD is fast, especially in the first 6–12 months, even with low doses of glucocorticoids, with trabecular bone being the most affected.<a class="elsevierStyleCrossRef" href="#bib1905">182</a> According to studies, the fractures associated with treatment with glucocorticoids appear with BMD which is not too low, due to the fact that the glucocorticoid mainly affects the whole bone micro architecture, and the TBS and FRAX® adjusted with TBS could have a certain additional usefulness in the assessment of the risk of these patients.<a class="elsevierStyleCrossRef" href="#bib1910">183</a> However, the application of the FRAX® in OP through glucocorticoids has certain limitations and underestimates the real risk of fracture, since it does not adjust from accumulated dose from daily dose or treatment duration.ACR recommendations consider that in patients who receive or are going to receive treatment with glucocorticoids the fracture risk must be assessed (preferably using FRAX®) and treatment initiation as soon as possible should be assessed. Furthermore, general preventative OP measures would have to be used in all patients, such as healthy life habits for bones and diet (see section on non pharmacological treatment, calcium and vitamin D). Furthermore, the lowest possible dose of glucocorticoid should be used and for as short a time as possible, and using immunosuppressants if necessary.<a class="elsevierStyleCrossRef" href="#bib1175">36</a>In patients with an intermittent corticoid regime and who have an accumulated dose of prednisone >5g/year or those with annual losses of BMD above 10% the panel of experts consider that treatment for OP would also be indicated.Premenopausal women or men <50 years of age are at a lower fracture risk. There are also fewer data on efficacy and safety or OP treatments for this population group and treatment indications appear to be more restrictive.The pharmacological treatment of choice is oral BP (risedronic acid and alendronic acid) or intravenous zoledronic acid since they stabilise or increase the BMD and reduce the risk of vertebral fractures in comparison with control groups.<a class="elsevierStyleCrossRef" href="#bib1915">184</a> According to the technical specifications, the drugs which currently have an glucocorticoid OP indication in Spain are teriparatide, risedronic acid and zoledronic acid.In women with established OP, teriparatide has been demonstrated to be more effective than risedronic acid in reducing vertebral fractures and clinical fractures, regardless of having received previous treatment with BP.<a class="elsevierStyleCrossRef" href="#bib1920">185</a> In fact, teriparatide has demonstrated superiority against alendronic acid in both gain in BMD and reduction in morphometric vertebral fractures, in premenopausal, postmenopausal women and men treated with glucocorticoids after 18 months of follow-up.<a class="elsevierStyleCrossRef" href="#bib1925">186</a> As a result, the panel of experts consider that high risk patients or those refractory or who have contraindications to antiresorptive treatment could evaluate the treatment with teriparatide.<a class="elsevierStyleCrossRef" href="#bib1230">47</a>In patients who start or have already received glucocorticoids, the administration of denosumab for 12 months has shown an increase in BMD which is significantly higher than with risedronic acid,<a class="elsevierStyleCrossRef" href="#bib1930">187</a> and the European Medicines Agency (EMA) has recommended that denosumab be added into the technical specification as a new indication: for treatment of the loss of BMD associated with the prolonged use of glucocorticoids in adult patients at high risk of fracture.According to the recommendations of the International Groups, the treatment of choice should be maintained for as long as treatment with glucocorticoids lasts and for at least 6 months after suspending the glucocorticoid, unless fractures exist, in which case it would be continued.<a class="elsevierStyleCrossRef" href="#bib1175">36</a>Rheumatic, inflammatory and systemic diseasesRecommendation:It is advisable to assess the risk of fracture and consider performing DXA in patients with rheumatoid arthritis, systemic lupus erythematosus and ankylosing spondylitis especially those over 50 years of age and who are being treated with glucocorticoids or with a severe or evolved disease (RR: √; AL: 100%).Patients with rheumatoid arthritis, systemic lupus erythematosus and ankylosing spondylitis are at greater risk of OP and/or fractures.<a class="elsevierStyleCrossRefs" href="#bib1935">188–194</a> One study reported an increased fracture risk in psoriasis arthritis and in severe psoriasis.<a class="elsevierStyleCrossRef" href="#bib1970">195</a> The conclusions of some studies in patients with rheumatoid arthritis advise screening for fragility fracture and performing rheumatoid DXA, especially in patients >50 years of age in those with severe disease or evolved disease or those treated with glucocorticoids.<a class="elsevierStyleCrossRefs" href="#bib1935">188,189</a> Moreover, several documents of consensus on the management of comorbidities in rheumatoid arthritis, psoriasis arthritis and systemic lupus erythematosus suggested making an accurate prophylaxis of OP.<a class="elsevierStyleCrossRefs" href="#bib1975">196–198</a> In relation to antifracture treatments, all the drugs approved for OP were used. In the case of denosumab, safety data was limited in patients treated with biologic agents for their baseline disease, although according to the outcome of some studies there does not appear to be a different safety profile from the postmenopausal OP one.<a class="elsevierStyleCrossRef" href="#bib1990">199</a>Osteoporosis in the maleRecommendation:The study of the causes of secondary osteoporosis in all men with low bone mass or fragility fracture is recommended (RR: D; AL: 100%).It has been observed in different studies that OP in the male is underdiagnosed.<a class="elsevierStyleCrossRef" href="#bib1995">200</a> in fact it has been estimated that a third of hip fractures worldwide occur in males, especially after the age of 70 years. Furthermore, mortality after a hip fracture (over 37% in the first year) is higher than that in women.<a class="elsevierStyleCrossRef" href="#bib2000">201</a> Also, in the male secondary OP is more frequent and studies therefore conclude that appropriate, accurate clinical assessment is needed for systematic exclusion. The most frequent OP causes and risk factors in the man are hypogonadism, alcohol consumption, tobacco and glucocorticoids. Fracture risk assessment in the male would include clinical risk factors, the existence of previous fractures and the measurement of BMD by DXA (if indicated) to better stratify those patients more susceptible for treatment.<a class="elsevierStyleCrossRef" href="#bib2005">202</a> With regard to DXA, the same reference values are used in men as in women.<a class="elsevierStyleCrossRef" href="#bib2010">203</a>With regard to non pharmacological prevention measures, the same may be considered as for OP in women. For hormonal treatment, there are no data on fracture reduction efficacy with testosterone treatment, and the experts therefore only indicate treatment in males with symptomatic hypogonadism and also advising it should be combined with another antiosteoporotic treatment.<a class="elsevierStyleCrossRef" href="#bib2015">204</a> The drugs which have shown improvement of BMD and reduction of vertebral risk fracture both in eugonadal and hypogonadal males are oral BP (alendronic acid and risedronic acid),<a class="elsevierStyleCrossRefs" href="#bib2020">205,206</a> zoledronic acid (the only one which was established as the primary aim)<a class="elsevierStyleCrossRef" href="#bib2030">207</a> and teriparatide.<a class="elsevierStyleCrossRefs" href="#bib2035">208,209</a> Denosumab was also approved in males with a high fracture risk and to reduce the loss of BMD in the patient with prostate cancer in androgen deprivation treatment.<a class="elsevierStyleCrossRef" href="#bib2045">210</a> All these drugs, except the alendronic acid, have an indication in Spain for OP in the male.Osteoporosis in premenopausal womenRecommendation:It is recommended that a study of secondary osteoporosis causes be made in all premenopausal women with a low bone mass measured by DXA or with a fragility fracture (RR: √; AL: 100%).According to the different scientific societies and expert groups, in the premenopausal woman a DXA should be carried out when there are fragility fractures and/or risk factors associated with the loss of bone mass.<a class="elsevierStyleCrossRefs" href="#bib1205">42,211</a> In this patient group the Z-score would have to be used (which compares with individuals of the same age and sex) instead of the T-score.<a class="elsevierStyleCrossRefs" href="#bib1205">42,211,212</a> Thus, “low bone mass” is considered when the Z-score is lower than −2 SD.<a class="elsevierStyleCrossRef" href="#bib2050">211</a> The presence of fragility fractures and particularly when associated with low bone mass, means that OP diagnosis may be established in the premenopausal woman.<a class="elsevierStyleCrossRef" href="#bib2055">212</a>Considering that over 50% of premenopausal women with OP present with a secondary OP<a class="elsevierStyleCrossRefs" href="#bib2055">212,213</a> the experts recommend making an exhaustive study to rule out an underlying cause,<a class="elsevierStyleCrossRefs" href="#bib2055">212,213</a> with the most frequent being the following: treatment with glucocorticoids, oestrogen deficit, malabsorption diseases and OP associated with pregnancy or breast feeding.<a class="elsevierStyleCrossRef" href="#bib2055">212</a> Idiopathic forms are frequent in premenopausal women and may be associated with hypercalciuria and with a family history of OP.<a class="elsevierStyleCrossRef" href="#bib2060">213</a>The therapeutic approach in the premenopausal woman includes optimum calcium and vitamin D intake, regular physical exercise, suspending tobacco consumption, limiting alcohol consumption and treating the underlying cause.<a class="elsevierStyleCrossRef" href="#bib2055">212</a>For premenopausal OP experts, the specific antiosteoporotic drugs (BP, teriparatide, denosumab) will be considered in patients with fragility fracture or for certain secondary causes such as treatment with glucocorticoids.<a class="elsevierStyleCrossRef" href="#bib2060">213</a> The drugs which they have studied in premenopausal OP are BP (alendronic acid and risedronic acid) and teriparatide.<a class="elsevierStyleCrossRef" href="#bib2055">212</a> According to experts, in young women certain caution should be used in the administration of BP given its long retention in the bone tissue, particularly in women who wish to get pregnant in the future. They also conclude that none of these drugs should be used in pregnancy (BP and teriparatide are in the C category according to the FDA).<a class="elsevierStyleCrossRefs" href="#bib2065">214,215</a> With regard to the SERM, it seems reasonable to avoid its use in premenopausal women, whilst with denosumab there is only an indication in postmenopausal OP (according to the FDA: category in pregnancy).<a class="elsevierStyleCrossRef" href="#bib2055">212</a>Some experts suggests that in fertile women anti conceptive measures should be prescribed if any antiosteoporotic treatment is initiated.<a class="elsevierStyleCrossRef" href="#bib2060">213</a>Other special situations: kidney disease, liver disease and digestive problemsChronic renal diseaseIn patients with chronic renal disease (CRD) certain differential aspects should be taken into consideration with postmenopausal OP: (1) DXA does not discriminate the type of underlying bone disease and (2) renal osteodystrophy should be excluded, particularly dynamic bone disease (very low osteodystrophy with remodelling) in chronic dialysis patients, since this contraindicates the use of antiresorptives. PTH levels <120pg/ml with low alkaline phosphatase suggest the presence of dynamic bone disease.<a class="elsevierStyleCrossRef" href="#bib2075">216</a>With regard to a deficiency of vitamin D in the CRD, in states 3–5D, the experts consider the use of therapeutic strategies similar to those accepted for the general population to be appropriate.Regarding antifracture treatments for stage 1–2 patients and filtered >35ml/min, its use is mostly similar to that of patients without CRD.<a class="elsevierStyleCrossRefs" href="#bib2080">217,218</a>The technical specifications of the drugs indicates that BP, teriparatide and raloxifene are not recommended when filtration is <30ml/min (<35ml/min for alendronic acid and zoledronic acid). However, some post hoc studies conducted with risedronic acid<a class="elsevierStyleCrossRef" href="#bib2090">219</a>and raloxifene<a class="elsevierStyleCrossRefs" href="#bib2095">220,221</a> in patients with glomerular filtration between 15 and 30ml/min (stage 4) have shown these drugs demonstrate most efficacy and safety. Notwithstanding, the limited evidence of this type of post hoc study must be borne in mind. Bazedoxifene has not been sufficiently documented in patients with filtration <30ml/min. Denosumab does not require dose adjustment in kidney failure, but the risk of hypocalcaemia is higher, and it is therefore advised to optimise calcium and vitamin D supplements. Evidence of their safety in patients with stage 4 CRD and in haemodialysis is also limited due to the post hoc studies having a limited number of patients.<a class="elsevierStyleCrossRef" href="#bib2105">222</a>Chronic liver diseaseAccording to the experts, patient management with chronic liver disease includes evaluation of factors which lead to bone loss and the increase in fracture risk such as malnutrition, vitamin D deficit, intensity of cholestasis, glucocorticoids and hypogonadism. The pharmacological studies of reduction in patients with liver disease are limited, with no contraindications existing for the use of BP, which increase BMD.<a class="elsevierStyleCrossRef" href="#bib2110">223</a> There is not enough experience with other treatments.Digestive diseasesStudies conclude that management of patients with celiac disease, inflammatory bowel disease, and bariatric surgery should consider malabsorption and malnutrition (evaluate calcium and vitamin D supplements), as well as the use of glucocorticoids. In inflammatory bowel disease the BP reduce the risk of vertebral fracture.<a class="elsevierStyleCrossRef" href="#bib2115">224</a>According to the data sheet, oral BP are contraindicated in patients with esophageal anomalies and other factors which may delay emptying, such as stenos is and acalasia. The panel of experts consider that when oral antiresorptive therapy is contraindicated, it is regarded as ineffective due to serious malabsorption is not tolerated, and parenteral route treatment may be considered.<a class="elsevierStyleCrossRef" href="#bib1230">47</a>New treatmentsTwo new drugs for OP treatment: romosozumab and abaloparatide are currently in an advanced phase of clinical development.Romosozumab is a humanised IgG2 monoclonal antibody which links and blocks sclerostin. It is administered monthly subcutaneously for a year, followed by denosumab or alendronic acid for a further year and has shown a significant reduction in the incidence of new vertebral and non vertebral fractures.<a class="elsevierStyleCrossRefs" href="#bib2120">225,226</a> in one of the studies an increase in the rate of serious adverse cardiovascular events was observed compared with alendronic acid,<a class="elsevierStyleCrossRef" href="#bib2125">226</a> which motivated a requirement by the US Food and Drug Administration (FDA) to provide the results of additional studies.Abaloparatide is a synthetic peptide which activate the type 1 receptor of the PTH, approved by the FDA in 2017 and rejected by the EMA in 2018. In daily subcutaneous administration it obtained a significant reaction in the rate of vertebral and non vertebral fractures compared with placebo, with no differences to teriparatide.<a class="elsevierStyleCrossRef" href="#bib2130">227</a> Its safety and tolerability profile was similar to teriparatide, but with a lower rate of hypercalcaemia.ConclusionAs mentioned in the introduction, the aim of this document was to provide an update on the new advances in the different aspects of OP relating to clinical practice: diagnosis, evaluation, treatment and follow-up.The document is based on a critical review of the previous consenus,<a class="elsevierStyleCrossRef" href="#bib1020">5</a> the best available scientific evidence and expert clinical experience. This was a joint task between panel members and the SER Unit of Research which, together with SER reviewers, carried out an extensive systematic review on the different areas of interest and provided the necessary scientific rigour to produce the recommendations with their level of evidence and also their level of consensus, to provide the reader with the most objective evaluation of these recommendations.The new definition of OP is incorporated into the diagnostic assessment of this document, and which encompasses patients with fragility fractures and low bone mass, the concept of imminent risk of fracture and the utility of TBS.With regard to treatment, the effectiveness of each drug for the prevention of fractures together with several selection criteria such as cost-effectiveness, the existence of multiple fractures or the limitations for oral use are presented. The panel members assessed the possibility of including an extensive treatment decision algorithm no agreement was reached on this.The SER reviewers for their part have updated osteonecrosis of the jawbone and atypical femur fracture guidelines. Special situations were maintained in keeping with the 2011 recommendations, adding OP of inflammatory rheumatisms and a few precautions which should be taken into account in patients with kidney disease and gastrointestinal and hepatic problems. Finally, a section on the new treatments (romosozumab and abaloparatide) was produced.We would like to highlight from these recommendations that fracture risk and treatment indication were the issues most debated among panel members. The use of the FRAX® was unanimously accepted for hip fracture with the threshold of 3% whilst the level of agreement for primary fracture was somewhat lower. In the document the reason why of this discrepancy was exposed, which was basically derived from the absence of sufficient studies on the calibration of the FRAX® for the Spanish population.To conclude, we may say that the recommendations of this document are a draft consultation framework for OP management. They are general regulations which require individualisation in each case and this is the role we must accept as professionals.Conflict of interestsAntonio Naranjo Hernández received financing from Amgen, Lilly and FAES for attendance to courses/congresses, fees from Amgen for congress presentations and grants from FHOEMO-Amgen and Lilly to contract staff and provide IT teams to the service.María Pilar Aguado Acín received financing from Lilly for attendance to congresses; fees from Alexion, Faes, Lilly and de Rubió for presentations and financing for educational programmes in the Rheumatology Unit.Luis Arboleya Rodríguez received financing from Janssen-Cilag, Lácer and Lilly for attendance at congresses and received fees from Pfizer and Lilly for congress presentations.Enrique Casado Burgos received financing from Amgen, Lilly, FAES, Gebro, ItalDrug and Rubió for attendance to courses/congresses and fees for presentations.Santos Castañeda Sanz received financing from Amgen for attendance to courses/congresses; fees from Lilly for congress presentations; and financial aid from Amgen for consultation for pharmaceutical companies or other technologies and for educational programmes or courses.Jodi Fitter Arrested received financing from Novartis, Roche, MSD, Amgen, Lilly, Maharani, UCB and Pfizer for attendance to courses/congresses; fees from Amgen-Ferrier, Roche, Maharani and Amgen for congress presentations and received financing from UCB to participate in a research study.Labia Gofer Sale received financing from Lilly for attendance to congresses; fees from Lilly, Amgen and FAES Farman e for congress presentations; and financing from Alexion for research projects.Carmen Gomez Vaquero received financing from Abby, Amgen, Bristol, Lilly, Maharani, MSD, Pfizer, Procter Gamble, Roche, Sandoz, Servicer, UCB for attendance to courses/congresses; fees from Abbie, Amgen, Lilly, MSD, Pierre Fabré, Roche and UCB for congress presentations; financing from Lilly for educational programmes or courses; financing from Novartis, Amgen and Lilly for participating in a research study; financial aid from Nycomed Pharma for consultation for pharmaceutical companies or other technologies; and received financing from Lilly for educational programmes or courses for the unit.Núria Guañabens Gay received financing from Amgen y Lilly for attendance to courses/congresses, for congress presentations and for educational programmes or courses; financing from Amgen to participate in a research study and financial aid from Lilly, Amgen, UCB y Alexion as consultation for pharmaceutical companies." "textoCompletoSecciones" => array:1 [ "secciones" => array:15 [ 0 => array:3 [ "identificador" => "xres1209516" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1126139" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1209515" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1126140" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction and objectives" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Methodology" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Design" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Procedural stages" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Structure" ] ] ] 6 => array:2 [ "identificador" => "sec0030" "titulo" => "Results" ] 7 => array:3 [ "identificador" => "sec0035" "titulo" => "Diagnosis and evaluation" "secciones" => array:6 [ 0 => array:2 [ "identificador" => "sec0040" "titulo" => "Definition and diagnosis" ] 1 => array:2 [ "identificador" => "sec0045" "titulo" => "Fracture risk factors" ] 2 => array:3 [ "identificador" => "sec0050" "titulo" => "Evaluation of fracture risk" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0055" "titulo" => "Bone densimetry" ] 1 => array:2 [ "identificador" => "sec0060" "titulo" => "Bone densitometry indications" ] 2 => array:2 [ "identificador" => "sec0065" "titulo" => "Trabecular Bone Score" ] ] ] 3 => array:2 [ "identificador" => "sec0070" "titulo" => "Analysis" ] 4 => array:2 [ "identificador" => "sec0075" "titulo" => "Bone turnover markers" ] 5 => array:2 [ "identificador" => "sec0080" "titulo" => "Vertebral fracture screening" ] ] ] 8 => array:3 [ "identificador" => "sec0085" "titulo" => "Treatment" "secciones" => array:11 [ 0 => array:2 [ "identificador" => "sec0090" "titulo" => "Non pharmacological therapies" ] 1 => array:2 [ "identificador" => "sec0095" "titulo" => "Calcium and vitamin D" ] 2 => array:2 [ "identificador" => "sec0100" "titulo" => "Treatment to prevent fractures" ] 3 => array:2 [ "identificador" => "sec0105" "titulo" => "Antifracture treatment choice" ] 4 => array:2 [ "identificador" => "sec0110" "titulo" => "Sequential and combined therapy" ] 5 => array:3 [ "identificador" => "sec0115" "titulo" => "Treatment duration" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0120" "titulo" => "Treatment suspension or discontinuation" ] 1 => array:3 [ "identificador" => "sec0125" "titulo" => "Follow-up, monitorisation and adherence" "secciones" => array:1 [ …1] ] ] ] 6 => array:2 [ "identificador" => "sec0135" "titulo" => "Monitorisation" ] 7 => array:2 [ "identificador" => "sec0140" "titulo" => "Therapy failure" ] 8 => array:2 [ "identificador" => "sec0145" "titulo" => "Treatment safety" ] 9 => array:2 [ "identificador" => "sec0150" "titulo" => "Osteonecrosis of the jawbones" ] 10 => array:2 [ "identificador" => "sec0155" "titulo" => "Atypical femur fracture" ] ] ] 9 => array:3 [ "identificador" => "sec0160" "titulo" => "Special situations" "secciones" => array:7 [ 0 => array:2 [ "identificador" => "sec0165" "titulo" => "Fragility fracture" ] 1 => array:3 [ "identificador" => "sec0170" "titulo" => "Vertebral fracture" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0175" "titulo" => "Vertebroplasty and kyphoplasty" ] ] ] 2 => array:2 [ "identificador" => "sec0180" "titulo" => "Osteoporosis from glucocorticoids" ] 3 => array:2 [ "identificador" => "sec0185" "titulo" => "Rheumatic, inflammatory and systemic diseases" ] 4 => array:2 [ "identificador" => "sec0190" "titulo" => "Osteoporosis in the male" ] 5 => array:2 [ "identificador" => "sec0195" "titulo" => "Osteoporosis in premenopausal women" ] 6 => array:3 [ "identificador" => "sec0200" "titulo" => "Other special situations: kidney disease, liver disease and digestive problems" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0205" "titulo" => "Chronic renal disease" ] 1 => array:2 [ "identificador" => "sec0210" "titulo" => "Chronic liver disease" ] 2 => array:2 [ "identificador" => "sec0215" "titulo" => "Digestive diseases" ] ] ] ] ] 10 => array:2 [ "identificador" => "sec0220" "titulo" => "New treatments" ] 11 => array:2 [ "identificador" => "sec0225" "titulo" => "Conclusion" ] 12 => array:2 [ "identificador" => "sec0230" "titulo" => "Conflict of interests" ] 13 => array:2 [ "identificador" => "xack413337" "titulo" => "Acknowledgements" ] 14 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2018-07-02" "fechaAceptado" => "2018-09-19" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1126139" "palabras" => array:6 [ 0 => "Osteoporosis" 1 => "Diagnosis" 2 => "Treatment" 3 => "Fracture" 4 => "Spanish Society of Rheumatology" 5 => "Recommendations" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1126140" "palabras" => array:6 [ 0 => "Osteoporosis" 1 => "Diagnóstico" 2 => "Tratamiento" 3 => "Fractura" 4 => "Sociedad Española de Reumatología" 5 => "Recomendaciones" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "ObjectiveTo update the recommendations on osteoporosis (OP) of the Spanish Society of Rheumatology (SER) based on the best possible evidence. MethodsA panel of nine expert rheumatologists in OP was created, previously selected by the SER through an open call. The phases of the work were: identification of the key areas for updating the previous consensus, analysis and synthesis of the scientific evidence (using the SIGN levels of evidence) and formulation of recommendations based on this evidence and consensus techniques. ResultsThis revision of the recommendations implies an update in the diagnostic evaluation and treatment of OP. It proposes some criteria to consider the high risk of fracture and some indications to start treatment. The recommendations also address issues related to the safety of treatments and the management of special situations such as inflammatory diseases and treatment with glucocorticoids. ConclusionsWe present an update of SER recommendations on OP." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "ObjetivoActualizar las recomendaciones sobre osteoporosis (OP) de la Sociedad Española de Reumatología (SER) basadas en la mejor evidencia posible. MétodosSe creó un panel formado por nueve reumatólogos expertos en OP previamente seleccionados por la SER mediante una convocatoria abierta. Las fases del trabajo fueron: identificación de las áreas claves para la actualización del consenso anterior, análisis y síntesis de la evidencia científica (utilizando los niveles de evidencia del SIGN) y formulación de recomendaciones a partir de esta evidencia y de técnicas de consenso. ResultadosEsta revisión de las recomendaciones comporta una actualización en la evaluación diagnóstica de la OP y de su tratamiento. Propone unos criterios para considerar alto riesgo de fractura y unas indicaciones para iniciar tratamiento. Las recomendaciones abordan también cuestiones relativas a la seguridad de los tratamientos y al manejo de situaciones especiales como las enfermedades inflamatorias y el tratamiento con glucocorticoides. ConclusionesSe presenta la actualización de las recomendaciones SER sobre OP." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Naranjo Hernández A, Díaz del Campo Fontecha P, Aguado Acín MP, Arboleya Rodríguez L, Casado Burgos E, Castañeda S, et al. Recomendaciones de la Sociedad Española de Reumatología sobre osteoporosis. Reumatol Clin. 2019;15:188–210." ] ] "apendice" => array:1 [ 0 => array:1 [ "seccion" => array:1 [ 0 => array:4 [ "apendice" => "<elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia>" "etiqueta" => "Annex 1" "titulo" => "Levels of evidence and SIGN recommendations" "identificador" => "sec0235" ] ] ] ] "multimedia" => array:11 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1489 "Ancho" => 2500 "Tamanyo" => 232769 ] ] "descripcion" => array:1 [ "en" => "Recommendations for initiating treatment for the prevention of fractures in patients with osteoporosis or risk of osteoporosis." ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1331 "Ancho" => 2500 "Tamanyo" => 190050 ] ] "descripcion" => array:1 [ "en" => "Recommendations to initiate prophylaxis or Op treatment in patients who will receive glucocorticoids in the following 3 months." ] ] 2 => array:8 [ "identificador" => "tbl0015" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "BMD: bone mineral density; FRAX®: Fracture Risk Assessment; AL: agreement level; RR: Recommendation rating (see <a class="elsevierStyleCrossRef" href="#sec0235">Appendix 1</a>)." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Recommendations \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">RR \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">AL \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="3" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Diagnosis and evaluation</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Recommendation: It is recommended that fragility fracture risk assessment should not be based exclusively on the measurement of BMD but should also take into account clinical risk factors. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">B \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">100% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Recommendation: The use of the FRAX®, tool is recommended, with or without BMD, to assess fracture risk. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">√ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">78% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Recommendation: The classification of patients into high fracture risk is recommended when the risk quantified by FRAX®for hip fracture is ≥3%. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">√ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">100% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Recommendation: To classify high risk patients using FRAX®for primary fracture it is recommended that the threshold used is ≥10% without BMD or ≥7.5% with BMD. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">√ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">78% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Recommendation: the use of densitometry is recommended in the following cases: \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="6" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">D</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1. Fragility fracture \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">100% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2. Presence of two or more high fracture risk factors \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">100% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3. FRAX® for primary fracture ≥5% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">78% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4. Treatment with aromatase inhibitor drugs, antiandrogen drugs and glucocorticoids \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">100% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5. Disease associated with secondary OP \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">100% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Recommendation: A basic analytical study is recommended to rule out secondary causes of osteoporosis. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">√ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">100% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Recommendation: The routine example of bone turnover markers is not established. However, they could be considered in the initial assessment and in follow-up of patients with osteoporosis. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">B \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">89% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Recommendation: Assessment of the presence of vertebral fractures is recommended in the high fracture risk patient or the patient with osteoporosis when kyphosis or significant height loss is perceived and when there is back pain or low back pain of recent onset. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">D \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">100% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="3" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="3" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Treatment</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Recommendation: A healthy lifestyle is recommended for the prevention of primary and secondary osteoporosis and fractures, including a balanced diet and regular physical exercise, avoidance of tobacco, limitation of alcohol consumption and the use of preventative measures for falls. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">√ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">100% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Recommendation: A daily intake of calcium between 1000 and 1200mg, most of which should be included in the regular diet. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">D \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">100% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Recommendation: The daily intake of 800UI of vitamin is recommended in the following cases: \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="6" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">D</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="6" align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">100%</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1. Patients with osteoporosis \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2. People over 65 years of age with fracture risk \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3. People with vitamin D deficiency \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4. People with limited exposure to sunlight \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5. People with inadequate calcium intake (under 700–800mg per day) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Recommendation: Initiation of pharmacological treatment is recommended to reduce the risk of osteoporotic fracture in the following situations. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="8" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">√</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1. Fragility fracture of vertebra or hip in patients >50 years of age \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">100% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2. Other fragility fractures in patients >50 years of age and with low bone mass (T-score <−1 SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">89% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3. OP defined by T-score ≤−25 SD in spine, femoral neck or hip, always considering age, BMD figures and other risk factors \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">100% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4. Patients with high risk of hip fracture according to FRAX® with BMD ≥3% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">100% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5. Men being treated with androgen deprivation and T-score ≤−2.5 SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">100% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6. Women in treatment with aromatase inhibitors and T-score ≤−2 SD or with a T-score <−1.5 SD and an additional risk factor, or with ≥2 risk factors without BMD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">78% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7. Patients who are going to receive glucocorticoids for over 3 months in the following cases: (a) initial dose ≥30mg/day of prednisone; (b) postmenopausal women and men >50 years of age with dose ≥5mg/day and previous fragility fracture or T-score ≤−1.5 SD or high risk of fracture: FRAX® for hip ≥3% or for primary fracture ≥10% without BMD or ≥7.5% with BMD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">100% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Recommendation: When selecting treatment, among other factors, it is recommended to consider: \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="9" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">√</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="9" align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">100%</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1. The efficacy and safety of the drugs \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2. The cost/effectiveness ratio \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3. The BMD value \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4. The presence of fractures, particularly vertebral or multiple fragility fractures \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5. Previous treatments and adherence to the same \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6. Age \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7. Comorbidities and polymedication \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8. Limitations for oral administration \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Recommendation: It is recommended that fracture risk be reassessed after 5 years of treatment with oral bisphosphonates or after 3 years of treatment with zoledronic acid. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">D \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">100% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Recommendation: When treatment with denosumab is suspended an alternative treatment for the osteoporosis must be considered. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">D \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">100% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Recommendation: In high fracture risk patients, including those with previous fragility fracture, or with a T-score of proximal femur <−.5 SD, it is not recommended to discontinue the osteoporosis treatment. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">D \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">89% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Recommendation: A periodical clinical assessment is recommended to confirm adherence to and efficacy of treatment, incidence of fractures and the possible appearance of adverse effects. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">√ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">100% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Recommendation: If the patient with OP has been subjected to any invasive dental procedure (extraction or implant) it is advised to postpone antiresorptive treatment initiation until the surgical wound has completely healed. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">D \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">100% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Recommendation: In patients treated with antiresorptives who are going to have a dental procedure it is not recommended to discontinue treatment with BP or denosumab. If risk factors additional to osteonecrosis of the jawbones exist or the surgical procedure is to be extensive temporary discontinuation of treatment with BP may be considered. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">D \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">78% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Recommendation: In patients with high fracture risk and prolonged treatment with bisphosphonates (>5 years for orals or >3 years for intravenous) it is recommended not to suspend treatment, since the risk of atypical femur fracture is very low and the benefits of fracture reduction greatly outweigh the risk of atypical fracture. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">D \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">100% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="3" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="3" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Special situations</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Recommendation: It is recommended that all patients ≥50 years of age with a recent fragility fracture be assessed systematically to prevent further fractures. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">D \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">100% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Recommendation: The treatment of choice for an acute vertebral fracture is rest, rapidly scaled analgesics to control pain, and if necessary the use of a brace. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">√ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">100% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Recommendation: Vertebroplasty and kyphoplasty are recommended for the treatment of vertebral fracture only in cases of serious refractory pain on a WHO analgesic scale, including opiates. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">D \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">100% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Recommendation: In patients who receive or who are going to receive treatment with glucocorticoids fracture risk must be assessed and the initiation of treatment for osteoporosis as soon as possible. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">D \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">100% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Recommendation: It is recommended that pharmacological treatment be initiated to prevent OP in patients who are going to receive glucocorticoids for over 3 months in the following cases: \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="9" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">D</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1. Patients with an initial dose ≥30mg/day of prednisone. In these cases it is recommended that treatment be imitated for OP immediately \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">100% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2. Postmenopausal women and men >50 years of age with a prednisone dose ≥5mg/day who also present with some of the following conditions: \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">100% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">a) Previous fragility fracture \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">89% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">b) Low BMD (T-score ≤−1.5 SD in spine or hip) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">78% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">c) High fracture risk: FRAX®for hip ≥3% or for primary fracture ≥10% without BMD or ≥7.5% with BMD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">100% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3. Premenopausal women and men <50 years of age and daily dose ≥7.5mg/of prednisone who also present with one of the following conditions: \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">78% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">a) Previous fragility fracture \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">78% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">b) Low BMD (Z-score ≤−3 SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Recommendation: It is advisable to assess the risk of fracture and consider performing DXA in patients with rheumatoid arthritis, systemic lupus erythematosus and ankylosing spondylitis especially those over 50 years of age and who are being treated with glucocorticoids or with a severe or evolved disease. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">√ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">100% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Recommendation: The study of the causes of secondary osteoporosis in all men with low bone mass or fragility fracture is recommended. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">D \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">100% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Recommendation: It is recommended that a study of secondary osteoporosis causes be made in all premenopausal women with a low bone mass or with a fragility fracture. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">√ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">100% \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2064904.png" ] ] ] ] "descripcion" => array:1 [ "en" => "SER recommendations on osteoporosis." ] ] 3 => array:8 [ "identificador" => "tbl0020" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Higher risk (relative risk ≥2) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Over 65 years of age \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Low weight: body mass index <20kg/m2 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Personal history of fragility fracture \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Maternal history of femur fracture \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Glucocorticoids (>5mg/day of prednisone or equivalent for >3 months) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">More than 2 falls in the last year \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Moderate risk (relative risk between 1and 2) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Active smoker \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Consumes >3units of alcohol per day<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Early menopause (<45 years of age), primary and secondary amenorrhea, hypogonadism in the male \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Diseases which may reduce BMD: rheumatoid arthritis and other inflammatory arthropathies, intestinal pathology, celiac disease, malabsorption, hepatopathies, hyperparathyroidism, anorexia and bulimia, solid organ transplant, etc. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Drugs with the ability to reduce BMD/increases the risk of fractures: hydantoins, antiretrovirals, anticonvulsants, aromatase inhibitors, androgen deprivation drugs, etc. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Conditions related to falls: eye conditions, neurological diseases (stroke, Parkinson), use of psychodrugs \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2064905.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "One unit of alcohol is equal to 200ml of beer or 100ml of wine or 25ml of a spirit." ] ] ] "descripcion" => array:1 [ "en" => "Clinical fracture risk factors." ] ] 4 => array:8 [ "identificador" => "tbl0025" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at3" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Cover nutritional requirements with a healthy diet which includes an adequate intake of proteins (0.8g per kilo of body weight), calcium, fruit and vegetables \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Limit caffeine intake \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Prudent exposure to sunlight \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Avoid consumption of tobacco and limited intake of alcohol to under 3 units per day<a class="elsevierStyleCrossRef" href="#tblfn0010">a</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Encourage physical activity with regular exercise both own weight bearing (examine: walking, dancing, practising taichi 30–40min per session) and muscle and postural strengthening, 3–4 days per week \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2064903.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "a" "nota" => "One unit of alcohol is equal to 200ml of beer or 100ml of wine or 25ml of a spirit." ] ] ] "descripcion" => array:1 [ "en" => "Main habits of a healthy lifestyle.<a class="elsevierStyleCrossRefs" href="#bib1260">53–57</a>" ] ] 5 => array:8 [ "identificador" => "tbl0030" "etiqueta" => "Table 4" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at4" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "ND: not demonstrated; PH: post hoc analysis by subgroups (designed after knowledge of the trial outcome); SG: subgroup analysis designed prior to knowing the trial outcome; SI: ITT (intention to try) analysis." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="3" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Vertebral</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Non vertebral</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Hip</th></tr><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Osteopenia \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Osteoporosis (no previous vertebral fracture) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Established Osteoporosis (with previous vertebral fracture) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Osteoporosis (no previous vertebral fracture) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Established Osteoporosis (with previous vertebral fracture) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Osteoporosis (no previous vertebral fracture) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Established Osteoporosis (with previous vertebral fracture) \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Alendronic acid<a class="elsevierStyleCrossRefs" href="#bib1410">83,84</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ND \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">SI \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">SI \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ND \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">SI \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">SG \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">SI \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Risedronic acid<a class="elsevierStyleCrossRefs" href="#bib1420">85,86</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ND \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">PH \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">SI \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ND \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">SI \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ND \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">SI \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Zoledronic acid<a class="elsevierStyleCrossRef" href="#bib1430">87</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ND \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">SI \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">SI \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ND \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">SI \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ND \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">SI \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Denosumab<a class="elsevierStyleCrossRef" href="#bib1435">88</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ND \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">SI \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">SG \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">SI \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ND \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">SI \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ND \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Teriparatide<a class="elsevierStyleCrossRef" href="#bib1440">89</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ND \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ND \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">SI \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ND \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">SI \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ND \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ND \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Ibandronic acid<a class="elsevierStyleCrossRef" href="#bib1445">90</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ND \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">SI \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ND \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">PH \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ND \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ND \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Raloxifene<a class="elsevierStyleCrossRef" href="#bib1450">91</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">PH \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">SI \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">SI \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ND \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">PH \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ND \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ND \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Bazedoxifene<a class="elsevierStyleCrossRef" href="#bib1455">92</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ND \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">SI \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">SI \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">PH \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">PH \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ND \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ND \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2064908.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Efficacy of the drugs to reduce vertebral, non vertebral and hip fracture." ] ] 6 => array:8 [ "identificador" => "tbl0035" "etiqueta" => "Table 5" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at5" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "SD: standard deviation; RF: risk factor; Fr: fracture; NNT: necessary number to treat; ARR: absolute risk reduction; RRR: relative risk reduction; T: T-score." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Study (duration) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Drug \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Baseline risk profile \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Mean age (years) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">RRR (%) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">RRA (%) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">NNT \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">FIT-1<a class="elsevierStyleCrossRef" href="#bib1410">83</a> (3 years) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Alendronic acid \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Vertebral Fr \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">71 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">47 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">FIT-2<a class="elsevierStyleCrossRef" href="#bib1415">84</a> (3 years) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Alendronic acid \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Without Vertebral Fr \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">68 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">44 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">60 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">BONE<a class="elsevierStyleCrossRef" href="#bib1445">90</a> (3 years) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Ibandronic acid \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Vertebral Fr \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">69 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">62 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">27 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">VERT NA<a class="elsevierStyleCrossRef" href="#bib1420">85</a> (3 years) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Risedronic acid \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Vertebral Fr \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">69 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">41 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">20 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">VERT MN<a class="elsevierStyleCrossRef" href="#bib1425">86</a> (3 years) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Risedronic acid \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Vertebral Fr \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">71 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">49 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="3" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HORIZON<a class="elsevierStyleCrossRef" href="#bib1430">87</a> (3 years)</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="3" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Zoledronic acid</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">T <−1.5 SD+Vertebral Fr \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="3" align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">73</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="3" align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">70</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="3" align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="3" align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">or \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">T <−2.5 SD±Vertebral Fr \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">MORE<a class="elsevierStyleCrossRef" href="#bib1450">91</a> (3 years)</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Raloxifene</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Vertebral Fr or \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="2" align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">67</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="2" align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">35</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="2" align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3.5</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="2" align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">16</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">T <−2.5 SD \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="3" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Silverman et al.<a class="elsevierStyleCrossRef" href="#bib1455">92</a> (3 years)</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="3" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Bazedoxifene</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Sin Vertebral Fr T <−2.5 SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="3" align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">67</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="3" align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">38</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="3" align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="3" align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">82</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">and >−4 SD \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">With Vertebral Fr T >−4 SD \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">FPT<a class="elsevierStyleCrossRef" href="#bib1440">89</a> (2 years) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Teriparatide \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Vertebral Fr \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">70 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">65 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">FREEDOM<a class="elsevierStyleCrossRef" href="#bib1435">88</a> (3 years) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Denosumab \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">T between −2.5 and −4 SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">72 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">67 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">20 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2064906.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Efficacy of treatments to reduce vertebral fracture. Reference studies used for the approval of each drug." ] ] 7 => array:8 [ "identificador" => "tbl0040" "etiqueta" => "Table 6" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at6" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "SD: standard deviation; RF: risk factor; Fr: fracture; NNT: necessary number to treat; ARR: absolute risk reduction; RRR: relative risk reduction; T: T-score." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Study (duration) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Drug \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Baseline risk profile \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Mean age (years of age) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">RRR (%) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">ARR (%) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">NNT \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">FIT-1 (3 years)<a class="elsevierStyleCrossRef" href="#bib1410">83</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Alendronic acid \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Vertebral Fr \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">71 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">20 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">FIT-2 (3 years)<a class="elsevierStyleCrossRef" href="#bib1415">84</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Alendronic acid \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Sin Vertebral Fr \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">68 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">VERT NA (3 years)<a class="elsevierStyleCrossRef" href="#bib1420">85</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Risedronic acid \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Vertebral Fr \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">69 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">40 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">31 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">VERT MN (3 years)<a class="elsevierStyleCrossRef" href="#bib1425">86</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Risedronic acid \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Vertebral Fr \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">71 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">33 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HIP (3 years)</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Risedronic acid</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Group 1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="2" align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">74</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="2" align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">20</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="2" align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.8</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="2" align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">55</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">T <−4 SD <−3 SD and RF \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="3" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HORIZON (3 years of age)<a class="elsevierStyleCrossRef" href="#bib1430">87</a></td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="3" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Zoledronic acid</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">T <−1.5 SD+Vertebral Fr \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="3" align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">73</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="3" align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">28</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="3" align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.7</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="3" align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">37</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">or \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">T <−2.5 SD±Vertebral Fr \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HORIZON-R<a class="elsevierStyleCrossRef" href="#bib1460">93</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Zoledronic acid \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Hip Fr \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">75 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">27 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">30 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">FPT (2 years)<a class="elsevierStyleCrossRef" href="#bib1440">89</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Teriparatide \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Vertebral Fr \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">70 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">35 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">34 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">FREEDOM (3 years)<a class="elsevierStyleCrossRef" href="#bib1435">88</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Denosumab \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">T between −2.5 and −4 SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">72 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">20 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">66 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2064899.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Efficacy of treatments to reduce non vertebral fracture. Reference studies used for the approval of each drug." ] ] 8 => array:8 [ "identificador" => "tbl0045" "etiqueta" => "Table 7" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at7" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "SD: standard deviation; RF: risk factor; Fr: fracture; NNT: necessary number to treat; ARR: absolute risk reduction; RRR: relative risk reduction; T: T-score." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Study (duration) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Drug \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Baseline risk profile \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Age (years) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">RRR (%) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">ARR (%) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">NNT \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">FIT-1<a class="elsevierStyleCrossRef" href="#bib1410">83</a> (3 years) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Alendronic acid \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Vertebral Fr \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">71 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">51 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">90 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HIP<a class="elsevierStyleCrossRef" href="#bib1465">94</a> (3 years)</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Risedronic acid</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Group 1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="2" align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">74</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="2" align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">40</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="2" align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.3</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="2" align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">77</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">T <−4 SD or <−3 SD and RF \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="5" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HORIZON<a class="elsevierStyleCrossRef" href="#bib1430">87</a> (3 years)</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="5" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Zoledronic acid</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Vertebral Fr+T< \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="5" align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">73</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="5" align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">41</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="5" align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.9</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="5" align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">109</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−1.5 SD \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">or \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">T <−2.5 SD±Fr \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">vertebral \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">FREEDOM<a class="elsevierStyleCrossRef" href="#bib1435">88</a> (3 years) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Denosumab \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">T <−2.5 and >−4 SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">72 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">39 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">230 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2064907.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Efficacy of treatments to reduce hip fracture. Reference studies used for the approval of each drug." ] ] 9 => array:5 [ "identificador" => "tbl0005" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => false "mostrarDisplay" => true "tabla" => array:2 [ "leyenda" => "Studies classified as 1− and 2− should not be used in the production of recommendations due to their high possibility of bias." "tablatextoimagen" => array:2 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Levels of evidence</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1++ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">High quality meta-analysis, systematic reviews of clinical trials or high quality clinical trials with very low risk of bias. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1+ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Well executed meta-analysis, systematic reviews of clinical trials or well executed clinical trials with low risk of bias. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1− \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Meta-analysis, systematic reviews of clinical trials or clinical trials with high risk of bias. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2++ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Systematic reviews of high quality cohort studies or cases and controls. Cohort studies or case and control studies with a very low risk of bias and high probability of establishing a causal relationship. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2+ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Well executed cohort studies or case and control studies with low risk of bias and a moderate probability of establishing a causal relationship. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2− \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Cohort studies or case and control studies with high risk of bias and significant risk that there will be no causal relationship. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Non analytical studies, such as case reports and case series. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Expert opinions. \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2064901.png" ] ] 1 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Recommendation rates</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">A \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">At least one meta-analysis, systematic review or clinical trial classified as 1++ and directly applicable to the target population of the guide; or a volume of scientific evidence composed by studies classified as 1+ and with major agreement between them. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">B \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">A volume of scientific evidence composed by studies classified as 2++, directly applicable to the target population of the guide and which show major concordance between them; or scientific evidence extrapolated from studies classified as 1++ or 1+. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">C \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">A volume of scientific evidence composed by studies classified as 2+, directly applicable to the target population of the guide and which shows major consistency between them; or scientific evidence extrapolated from studies classified as 2++. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">D \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Scientific evidence level 3 or 4; or scientific evidence extrapolated from studies classified as 2+. \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2064902.png" ] ] ] ] ] 10 => array:5 [ "identificador" => "tbl0010" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => false "mostrarDisplay" => true "tabla" => array:2 [ "leyenda" => "aOn occasions the drafting group notices an important practical aspect which has to be highlighted and for which there is probably no supporting evidence. In general, these cases concern some aspect of treatment which is considered good clinical practice and which nobody would usually question. These aspects are valued as points of good clinical practice. These messages are not an alternative to the recommendations based on evidence but should only be considered when there is no other way of highlight this aspect." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Good clinical practice</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">√ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Recommended practice based on clinical experience and consensus of the drafting team \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2064900.png" ] ] ] ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" 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Special Article

Recommendations by the Spanish Society of Rheumatology on Osteoporosis

Recomendaciones de la Sociedad Española de Reumatología sobre osteoporosis

Antonio Naranjo Hernándeza,

Corresponding author

anarher@gobiernodecanarias.org

Corresponding author.

, Petra Díaz del Campo Fontechab, María Pilar Aguado Acínc, Luis Arboleya Rodríguezd, Enrique Casado Burgose, Santos Castañedaf, Jordi Fiter Arestég, Laia Gifreh, Carmen Gómez Vaqueroi, Gloria Candelas Rodríguezk,l, Félix Manuel Francisco Hernándeza,l, Núria Guañabens Gayj

a Servicio de Reumatología, Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas de Gran Canaria, Spain

b Unidad de Investigación, Sociedad Española de Reumatología, Madrid, Spain

c Servicio de Reumatología, Hospital Universitario La Paz, Madrid, Spain

d Sección de Reumatología, Hospital Universitario Central de Asturias, Oviedo, Spain

e Servicio de Reumatología, Hospital Universitari Parc Taulí (UAB), Sabadell, Barcelona, Spain

f Servicio de Reumatología, IIS Princesa, Madrid, Spain

g Servicio de Reumatología, Hospital Universitario Son Espases, Palma de Mallorca, Spain

h Servicio de Reumatología, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain

i Servicio de Reumatología, Hospital Universitari de Bellvitge, Hospitalet de Llobregat, Barcelona, Spain

j Servicio de Reumatología, Hospital Clínic, Barcelona, Spain

k Servicio de Reumatología, Hospital Universitario Clínico San Carlos, Madrid, Spain

l Grupo de Revisores de Evidencia de la SER, Madrid, Spain

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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction and objectives</span><p id="par0005" class="elsevierStylePara elsevierViewall">Osteoporosis &#40;OP&#41; is a diffuse skeletal disorder characterised by a general reduction in bone strength leading to a higher risk of fracture due to fragility&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">In Spain and in other countries the rate of fragility fractures is increasing&#44; mainly due to higher life expectancies&#46;<a class="elsevierStyleCrossRef" href="#bib1000"><span class="elsevierStyleSup">1</span></a> One study reported that in 2010 2&#46;4 million Spaniards &#40;1&#46;9 million women and 0&#46;5 men&#41; over 50 suffered from OP&#44;<a class="elsevierStyleCrossRef" href="#bib1005"><span class="elsevierStyleSup">2</span></a> and as a consequences of this there were 204&#44;000 new fractures at a cost of 2842 million euros &#40;2&#46;8&#37;of the total healthcare costs in Spain&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib1010"><span class="elsevierStyleSup">3</span></a> It has been estimated that in 2025 there will be an 40&#37; increase in the rate of fractures and a 30&#37; increase in costs&#46;<a class="elsevierStyleCrossRef" href="#bib1010"><span class="elsevierStyleSup">3</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Recent years have witnessed advances in the diagnosis and treatment of OP but only a minority of patients with high fracture risk are being accurately assessed and treated in keeping with the recommendations of clinical practice guidelines&#46;<a class="elsevierStyleCrossRef" href="#bib1015"><span class="elsevierStyleSup">4</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">This document contains the updated recommendations of the Spanish Society of Rheumatology &#40;Spanish acronym&#58; SER&#41; on OP from the previous ones of 2011&#46;<a class="elsevierStyleCrossRef" href="#bib1020"><span class="elsevierStyleSup">5</span></a> These recommendations aim at helping physicians take decision for the management of post-menopausal OP and secondary OP &#40;glucocorticoids&#44; inflammatory diseases&#44; OP of the male and other clinical forms&#41;&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Methodology</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Design</span><p id="par0025" class="elsevierStylePara elsevierViewall">Qualitative synthesis of scientific evidence and consensus techniques have been used in this project which reflect the agreement by experts based on their clinical experience and scientific evidence&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Procedural stages</span><p id="par0030" class="elsevierStylePara elsevierViewall">A series of steps were taken during the development of the recommendations document&#44; which were&#58;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">1&#46;</span><p id="par0035" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Creation of the work group</span>&#46; The document began with the formation of a panel of experts formed by 9 SER member rheumatologists&#46; They were selected through an open call to all SER members&#46; The Clinical practice Guideline and Recommendations Committee &#40;Spanish acronym&#58; GPC&#41; of the SER assessed the curriculum vitae of all applicants&#44; in accordance with objective criteria of contribution to knowledge on OP&#44; taking into consideration publications in significant journals over the last 5 years&#46; Coordination of clinical and methodological aspects was made&#44; respectively&#44; by one of these rheumatologists as the main researcher &#40;MR&#41; and a methodology specialist executive from the Research Unit of the SER&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">2&#46;</span><p id="par0040" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Identification of the key areas for updating of the previous agreement</span>&#46; All workgroup members were involved in giving shape to the document&#44; and in establishing its content and key aspects&#46; First they identified the clinical questions of research which could have the greatest impact in offering information on OP management&#58; diagnosis&#44; assessment&#44; prevention&#44; treatment and special circumstances&#46; After this&#44; they decided which of these required a response through the formulation of a PICO question &#40;patient&#44; intervention&#44; comparison&#44; and outcome&#41;&#46; The methodology to be followed in the recommendation creation process was also defined&#46;</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">3&#46;</span><p id="par0045" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Literature review search</span>&#46; To respond to the non PICO clinical questions an updated systematic review &#40;SR&#41; search and GPC was made in MEDLINE and specialised sources in guidelines&#46; The other clinical questions were reformatted in four questions with the PICO format&#46; To respond to the PICO questions a search strategy was designed and a review of scientific evidence was made of studies published up until May 2017&#46; The following databases were used&#58; PubMed &#40;MEDLINE&#41;&#44; EMBASE and Cochrane Library &#40;Wiley Online&#41;&#46; The process was completed with a reference manual&#44; posters and congress abstracts search which the reviewers and experts considered to be of interest&#46;</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">4&#46;</span><p id="par0050" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Analysis and synthesis of scientific evidence</span>&#46; The SR and GPC identified for the non PICO questions were assessed by the methodology coordinator&#46; It was agreed that only those of high quality were considered apt for their incorporation as a source of evidence&#46; Two rheumatologists from the workgroup of SER evidence reviewers were responsible for systematically reviewing the scientific evidence available for the PICO questions&#46; After a critical reading of the complete test of the selected studies for each review&#44; they drew up a summary using a homogenised formula including tables and texts to describe the methodology&#44; results and quality of each study&#46; They made in-depth notes on the reasons for exclusion of articles not included in the selection&#46; The overall level of the scientific evidence was assessed using the <span class="elsevierStyleItalic">Scottish Intercollegiate Guidelines Network</span> &#40;SIGN&#41; &#40;see <a class="elsevierStyleCrossRef" href="#sec0235">Appendix 1</a>&#41; evidence levels&#46;</p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">5&#46;</span><p id="par0055" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Formulation of recommendations</span>&#46; When the critical reading was completed&#44; the MR and the panel of experts proceeded with the formulation of specific recommendations based on the available scientific evidence&#46; This formulation was based on &#8220;formal assessment&#8221; or &#8220;reasoned judgement&#44;&#8221; previously summarising the evidence for each of the clinical questions&#46; They also took into account quality&#44; quantity and consistency of the scientific evidence&#44; the generality of the results&#44; its applicability and its clinical impact&#46; For the formulation of the recommendations two rounds of consensus were used&#46; First&#44; with the &#8220;reasoned judgement&#8221; system&#44; where all of the experts drafted and discussed the recommendations&#46; Then&#44; in the presence of the methodologist&#44; using the modified technique of nominal consensus&#44; the level of agreement of the experts with the drafting of each recommendation was agreed upon&#46; It was established that there was a high level of consensus when the percentage of experts who agreed with the recommendation draft was 75&#37; or above&#46; The agreement was evaluated using a dichotomous reply &#40;yes&#58; agreed with the wording&#59; no&#58; disagreed with the wording&#41;&#46; Grading of the recommendations was made with the SIGN system &#40;see <a class="elsevierStyleCrossRef" href="#sec0235">Appendix 1</a>&#41;&#46; The recommendations were divided into four main areas&#58; diagnosis and evaluation&#59; treatment&#59; special circumstances&#59; new treatments&#46;</p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">6&#46;</span><p id="par0060" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Public exposure</span>&#46; The draft of this document of SER recommendations was submitted to a process of public exposure by the members of SER and different interest groups &#40;pharmaceutical industry&#44; other scientific societies and patient associations&#41; aimed at receiving scientific evaluation and discussion of its methodology and recommendations&#46; The complete information of this process is found in the appendix to the SER web site &#40;<a href="http://www.ser.es/">www&#46;ser&#46;es</a>&#41;&#44; in the section under SER Research and Recommendations&#46;</p></li></ul></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Structure</span><p id="par0065" class="elsevierStylePara elsevierViewall">The document includes all the formulated recommendations subdivided into the different above-mentioned areas&#46; Management algorithms were formulated from the recommendations and these offer a summarised approach to the treatment of OP&#46;</p></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Results</span><p id="par0070" class="elsevierStylePara elsevierViewall">There is a total of 28 formulated recommendations on OP &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Diagnosis and evaluation</span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Definition and diagnosis</span><p id="par0075" class="elsevierStylePara elsevierViewall">OP is a diffuse skeletal disease characterised by a reduction in bone resistance which leads to a higher risk of fragility fractures&#46; The concept of &#8220;bone resistance&#8221; encompasses factors relating both to bone mineral density &#40;BMD&#41; and the quality of the bone tissue&#46;<a class="elsevierStyleCrossRef" href="#bib1025"><span class="elsevierStyleSup">6</span></a></p><p id="par0080" class="elsevierStylePara elsevierViewall">A fragility fracture is that brought on by a low impact trauma&#46; A fall&#44; standing up or being seated would be included in this concept&#46; The most frequent and relevant fractures are those of the proximal femur&#44; the spine and the distal forearm&#46;<a class="elsevierStyleCrossRef" href="#bib1030"><span class="elsevierStyleSup">7</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">OP may be defined in any of the following circumstances&#58;<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">a&#41;</span><p id="par0090" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">T</span>-score in spine columnar&#44; femoral neck or total hip &#8804;&#8722;2&#46;5 SD&#46;</p></li><li class="elsevierStyleListItem" id="lsti0040"><span class="elsevierStyleLabel">b&#41;</span><p id="par0095" class="elsevierStylePara elsevierViewall">Femoral fracture due to fragility&#44; regardless of the BMD value&#44; in postmenopausal women and in men &#62;50 years of age&#46;</p></li><li class="elsevierStyleListItem" id="lsti0045"><span class="elsevierStyleLabel">c&#41;</span><p id="par0100" class="elsevierStylePara elsevierViewall">Fracture due to fragility of the spine&#44; proximal humerus or pelvis in postmenopausal women and in men &#62;50 years of age&#44; if there is a low BMD &#40;<span class="elsevierStyleItalic">T</span>-score &#60;&#8722;1&#46;0<span class="elsevierStyleHsp" style=""></span>SD&#41;&#46;</p></li></ul></p><p id="par0105" class="elsevierStylePara elsevierViewall">The conceptual definition of OP by the World Health Organisation &#40;WHO&#41; is solely based on the results of the BMD&#46; An individual has OP if the <span class="elsevierStyleItalic">T</span>-score in lumbar spine&#44; femoral neck or total hip is equal to or under &#8722;2&#46;5 standard deviation &#40;SD&#41; compared with the population peak bone mass&#46;<a class="elsevierStyleCrossRefs" href="#bib1035"><span class="elsevierStyleSup">8&#44;9</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">In normal clinical practice this definition fails to be operative due to many fragility fractures occurring in patients with a <span class="elsevierStyleItalic">T</span>-score &#62;&#8722;2&#46;5 SD&#46; For this reason the <span class="elsevierStyleItalic">National Bone Health Alliance</span> has proposed the consideration diagnosing OP in postmenopausal women and in men &#62;50 years of age with femoral fracture caused by fragility&#44; regardless of the BMD value&#44; and also when there is a low impact spinal fracture&#44; of the proximal humerus or the pelvis&#44; if the <span class="elsevierStyleItalic">T</span>-score &#60;&#8722;1&#46;0 SD&#46;<a class="elsevierStyleCrossRef" href="#bib1045"><span class="elsevierStyleSup">10</span></a> Doubts exist regarding forearm fracture&#44; which in some cases could be included depending on age or the mechanism of the fracture&#46; The authors also included OP diagnosis for the American population a quantified risk with the <span class="elsevierStyleItalic">Fracture Risk Assessment</span> &#40;FRAX<span class="elsevierStyleSup">&#174;</span>&#41; for the primary fracture &#8805;20&#37; &#40;proximal humerus&#44; forearm&#44; hip or clinical spine fracture&#41; or a risk of femoral fracture &#8805;3&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib1045"><span class="elsevierStyleSup">10</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">In view of the recommendations of these groups of experts and in accordance with clinical experience&#44; the panel of experts considered it appropriate to include postmenopausal women and men &#62;50 years of age with fragility fracture of the femur &#40;regardless of BMD&#41; in the OP diagnosis&#44; as well as spinal fracture&#44; fracture of the humerus or the pelvis&#44; if it was accompanied by low bone mass &#40;AL&#58; 89&#37;&#41;&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Fracture risk factors</span><p id="par0120" class="elsevierStylePara elsevierViewall">The main aim in OP management is fracture prevention and it is therefore essential to identify those individuals with the highest risk of presenting with them&#46;<a class="elsevierStyleCrossRef" href="#bib1050"><span class="elsevierStyleSup">11</span></a></p><p id="par0125" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0020">Table 2</a> describes high fracture risk factors &#40;RF&#41; &#40;relative risk &#8805;2&#41; and moderate RF &#40;relative risk 1&#8211;2&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib1020"><span class="elsevierStyleSup">5</span></a></p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><p id="par0130" class="elsevierStylePara elsevierViewall">Several risk factors&#44; such as age&#44; fracture history and the use of glucocorticoids&#44; among others contribute to the risk of fracture regardless of the BMD&#46; Patients with a recent fracture are at a particularly high risk of suffering from a new fracture&#46;<a class="elsevierStyleCrossRef" href="#bib1050"><span class="elsevierStyleSup">11</span></a></p><p id="par0135" class="elsevierStylePara elsevierViewall">The term &#8220;imminent fracture risk&#8221; has recently been proposed to refer to patents with a short term highs risk&#44; such as those with a recent fracture&#44; elderly fragile people with frequent falls or people treated with glucocorticoids at high level doses&#46;<a class="elsevierStyleCrossRefs" href="#bib1055"><span class="elsevierStyleSup">12&#44;13</span></a></p><p id="par0140" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">Recommendation&#58;</span><span class="elsevierStyleItalic">It is recommended that evaluation of fracture risk due to fragility should not be exclusively based on BMD figures but also bear in mind clinical risk factors</span> &#40;RR&#58; B&#59; AL&#58; 100&#37;&#41;&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">The combination of the BMD with clinical RF provides the best estimation of fracture risk&#46;<a class="elsevierStyleCrossRefs" href="#bib1065"><span class="elsevierStyleSup">14&#44;15</span></a> This has led to the development of fracture risk calculation tools which are able to include many factors&#46; Among the most popular and widely used is the FRAX<span class="elsevierStyleSup">&#174;</span>&#46;<a class="elsevierStyleCrossRef" href="#bib1040"><span class="elsevierStyleSup">9</span></a></p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Evaluation of fracture risk</span><p id="par0150" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">Recommendation&#58;</span><span class="elsevierStyleItalic">It is recommended that the tool FRAX</span><span class="elsevierStyleSup"><span class="elsevierStyleItalic">&#174;</span></span><span class="elsevierStyleItalic">be used&#44; with or without BMD&#44; to assess the fracture risk</span> &#40;RR&#58; &#8730;&#59; AL&#58; 78&#37;&#41;&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">The FRAX<span class="elsevierStyleSup">&#174;</span> calculates the probability of presenting a primary fracture &#40;this include hip&#44; clinical spine&#44; humerus and forearm&#41; or a hip fracture in the following 10 years&#44; with the inclusion or non inclusion of the BMD score&#46; When the BMD is included in the FRAX<span class="elsevierStyleSup">&#174;</span> tool the prediction of fracture risk is more precise and reliable&#46;<a class="elsevierStyleCrossRefs" href="#bib1075"><span class="elsevierStyleSup">16&#44;17</span></a></p><p id="par0160" class="elsevierStylePara elsevierViewall">FRAX<span class="elsevierStyleSup">&#174;</span> limitations are mostly determined by insufficiencies in the data from which it was calculated&#46; Thus the FRAX<span class="elsevierStyleSup">&#174;</span> does not consider the dose-response factor for several RF&#44; nor lumbar BMD&#44; nor the greater risk of fracture in patients with a recent fracture&#44; and it does not encompass falls&#46;<a class="elsevierStyleCrossRefs" href="#bib1040"><span class="elsevierStyleSup">9&#44;16&#8211;18</span></a></p><p id="par0165" class="elsevierStylePara elsevierViewall">The Spanish version of the FRAX<span class="elsevierStyleSup">&#174;</span> underestimates the risk of the primary fracture&#46;<a class="elsevierStyleCrossRef" href="#bib1090"><span class="elsevierStyleSup">19</span></a> However&#44; the application of a decision algorithm with bone densimetry threshold indication &#40;DXA&#41; and treatment based on FRAX<span class="elsevierStyleSup">&#174;</span> has been shown to be cost-effective with regard to the exclusive use of <span class="elsevierStyleItalic">T</span>-score &#8722;2&#46;5<span class="elsevierStyleHsp" style=""></span>SD&#46;<a class="elsevierStyleCrossRef" href="#bib1095"><span class="elsevierStyleSup">20</span></a> Despite its limitations&#44; the current version of the Spanish FRAX<span class="elsevierStyleSup">&#174;</span> may help to classify patients better with regard to fracture risk&#46;</p><p id="par0170" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">Recommendation&#58;</span><span class="elsevierStyleItalic">It is recommended that patients be classified as high fracture risk when the risk quantified by FRAX</span><span class="elsevierStyleSup"><span class="elsevierStyleItalic">&#174;</span></span><span class="elsevierStyleItalic">for hip fracture is &#8805;3&#37;</span> &#40;RR&#58; &#8730;&#59; AL&#58; 100&#37;&#41;&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">Recommendation&#58;</span><span class="elsevierStyleItalic">To classify patients as high risk using the FRAX</span><span class="elsevierStyleSup"><span class="elsevierStyleItalic">&#174;</span></span><span class="elsevierStyleItalic">for the primary fracture it is suggested that the threshold &#8805;10&#37; without BMD be used or &#8805;7&#46;5&#37; with BMD</span> &#40;RR&#58; &#8730;&#59; AL&#58; 78&#37;&#41;&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">The validity of the Spanish FRAX<span class="elsevierStyleSup">&#174;</span> was analysed in two prospective cohorts studies and in both the primary fracture risk was underestimated&#46; The relationship between observed fractures and expected fractures was 2&#46;2 in the FRIDEX<a class="elsevierStyleCrossRef" href="#bib1095"><span class="elsevierStyleSup">20</span></a> study and 1&#46;5 in the ECOSAP<a class="elsevierStyleCrossRef" href="#bib1100"><span class="elsevierStyleSup">21</span></a> Study&#46; However&#44; the estimation of the Spanish FRAX<span class="elsevierStyleSup">&#174;</span> for hip fracture appears to be appropriate&#46; A workgroup estimated the thresholds of the FRAX<span class="elsevierStyleSup">&#174;</span> in the Spanish population<a class="elsevierStyleCrossRefs" href="#bib1095"><span class="elsevierStyleSup">20&#44;22&#44;23</span></a> defining high primary fracture risk as a FRAX<span class="elsevierStyleSup">&#174;</span>&#44; with or without BMD&#44; &#8805;7&#46;5&#37; and intermediate risk between 5&#37; and 7&#46;5&#37;&#46; This was a single study which defined risk thresholds in Spain and had methodological limitations such as not being validated in regions other than Catalonia&#44; including only 8&#46;9&#37; of subjects with intermediate risk and 8&#46;5&#37; with high fracture risk&#44; as well as overlapping in the confidence interval of the high risk threshold&#46; In this sense&#44; the panel considers that a women aged around 70 years with a prior fracture &#40;is approximately equivalent to as Spanish FRAX<span class="elsevierStyleSup">&#174;</span> for the principal fracture without BMD of 10&#37;&#41; is an example of high fracture risk&#46;</p><p id="par0185" class="elsevierStylePara elsevierViewall">From the scarce evidence and low level of agreement in classifying the patient as high fracture risk based on the FRAX<span class="elsevierStyleSup">&#174;</span>&#44; the panel of experts agreed to consider a high risk fracture as FRAX<span class="elsevierStyleSup">&#174;</span> &#8805;3&#37; for a hip fracture&#46; Since no further studies on the FRAX<span class="elsevierStyleSup">&#174;</span> thresholds and&#47;or national official positioning were available&#44; the panel of experts also considered high fracture risk a FRAX<span class="elsevierStyleSup">&#174;</span> for primary fracture &#8805;10&#37; without BMD or &#8805;7&#46;5&#37; with BMD&#46;</p><p id="par0190" class="elsevierStylePara elsevierViewall">The panel of experts also considered as high fracture risk&#44; but without reaching an acceptable level of agreement &#40;AL&#58; 55&#37;&#41;&#44; the combination of two or more high RF&#46; Should the FRAX<span class="elsevierStyleSup">&#174;</span> tool not be used&#44; the presence of two high risk factors may serve as the starting point for assessing the BMD&#46;</p><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Bone densimetry</span><p id="par0195" class="elsevierStylePara elsevierViewall">The technique of choice today for measuring BMD is the DXA dual energy X-ray absorptiometry&#46;<a class="elsevierStyleCrossRefs" href="#bib1025"><span class="elsevierStyleSup">6&#44;10&#44;11</span></a> The measurement is made in the lumbar spine and the proximal femur &#40;femoral neck and total hip&#41;&#46; According to the experts&#44; measurement using DXA of the distal third of the forearm should only be performed when measurement in the lumbar spine or the proximal femur is not feasible and&#47;or in specific pathologies such as hyperparathyrodism&#46;<a class="elsevierStyleCrossRef" href="#bib1115"><span class="elsevierStyleSup">24</span></a></p><p id="par0200" class="elsevierStylePara elsevierViewall">The DXA has a high specificity for the reduction of fracture risk&#44; but a low sensitivity&#46; The risk increases exponentially as the BMD descends&#46;<a class="elsevierStyleCrossRef" href="#bib1120"><span class="elsevierStyleSup">25</span></a> However&#44; the majority of fragility fractures occur in patients with a <span class="elsevierStyleItalic">T</span>-score above &#8722;2&#46;5 SD&#46; Studies made in patients diagnosed with OP using DXA and without other RF of fractures conclude that it could be appropriate to estimate risk using FRAX<span class="elsevierStyleSup">&#174;</span> before evaluating treatment&#46;<a class="elsevierStyleCrossRefs" href="#bib1125"><span class="elsevierStyleSup">26&#44;27</span></a></p><p id="par0205" class="elsevierStylePara elsevierViewall">Different groups of experts agree that the BMD determined in the peripheral skeleton using DXA of the phalanx and heel spur and the ultrasound technique of the heel spur may be useful for prediction of fracture risk but not for diagnosing OP&#46;<a class="elsevierStyleCrossRefs" href="#bib1135"><span class="elsevierStyleSup">28&#44;29</span></a></p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Bone densitometry indications</span><p id="par0210" class="elsevierStylePara elsevierViewall">Criteria for requesting a DXA vary widely nationally and internationally&#46; The majority of international guidelines on OP recommend evaluation of BMD in postmenopausal women &#8805;65 years of age&#44; regardless of other RF&#46;<a class="elsevierStyleCrossRefs" href="#bib1145"><span class="elsevierStyleSup">30&#8211;32</span></a> There is controversy regarding the screening age in males&#46; The <span class="elsevierStyleItalic">National Osteoporosis Foundation</span> &#40;NOF&#41; and the <span class="elsevierStyleItalic">International Society for Clinical Densitometry</span> &#40;ISCD&#41; recommend measurement in males &#8805;70 years of age&#44; whilst the Canadian guidelines put the threshold at &#8805;65 years of age&#46;<a class="elsevierStyleCrossRef" href="#bib1150"><span class="elsevierStyleSup">31</span></a></p><p id="par0215" class="elsevierStylePara elsevierViewall">According to the conclusions of a cross-sectional study the aim of which was to evaluate DNX indication criteria in postmenopausal Spanish women based on the FRAX<span class="elsevierStyleSup">&#174;</span> tool&#44; the indication of the test should be based on clinical criteria to allow for patients to be selected where its evaluation is more efficient&#46;<a class="elsevierStyleCrossRef" href="#bib1160"><span class="elsevierStyleSup">33</span></a> The authors conclude that the strategy should begin with calculation of the fracture risk according to clinical RF&#44; and in this setting using FRAX<span class="elsevierStyleSup">&#174;</span><a class="elsevierStyleCrossRef" href="#bib1160"><span class="elsevierStyleSup">33</span></a> could be helpful&#46;</p><p id="par0220" class="elsevierStylePara elsevierViewall">Based on the accepted international recommendations on DXA indications&#44; the panel of experts considers that its main applications in clinical practice are&#58; OP diagnosis&#44; evaluation of fracture risk&#44; evaluation of treatment and monitorisation of response to treatment&#46;</p><p id="par0225" class="elsevierStylePara elsevierViewall">In patients with an imminent risk of fracture performing a DXA should not impede treatment initiation&#46; Thus patients with a high fracture risk may be treated without the need to carry out a DXA&#44; although it seems appropriate to know the baseline BMD for evaluation of treatment effectiveness at a later date&#46; The panel of experts agree that when the fracture risk is low no DXA should be performed and that a DNA should not be recommended to all women going through the menopause&#46;</p><p id="par0230" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">Recommendation&#58;</span><span class="elsevierStyleItalic">It is recommended to perform a densitometry in the following cases</span> &#40;RR&#58; D&#41;&#58;<ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0050"><span class="elsevierStyleLabel">1&#46;</span><p id="par0235" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Fragility fracture &#40;AL&#58; 100&#37;&#41;&#46;</span></p></li><li class="elsevierStyleListItem" id="lsti0055"><span class="elsevierStyleLabel">2&#46;</span><p id="par0240" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Presence of two or more high risk fracture factors &#40;AL&#58; 100&#37;&#41;&#46;</span></p></li><li class="elsevierStyleListItem" id="lsti0060"><span class="elsevierStyleLabel">3&#46;</span><p id="par0245" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">FRAX</span><span class="elsevierStyleSup"><span class="elsevierStyleItalic">&#174;</span></span><span class="elsevierStyleItalic">for primary fracture &#8805;5&#37; &#40;AL&#58; 78&#37;&#41;&#46;</span></p></li><li class="elsevierStyleListItem" id="lsti0065"><span class="elsevierStyleLabel">4&#46;</span><p id="par0250" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Treatment with aromatase inhibitor drugs&#44; antiandrogens and glucocorticoids &#40;AL&#58; 100&#37;&#41;&#46;</span></p></li><li class="elsevierStyleListItem" id="lsti0070"><span class="elsevierStyleLabel">5&#46;</span><p id="par0255" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Diseases associated with secondary OP &#40;AL&#58; 100&#37;&#41;&#46;</span></p></li></ul></p><p id="par0260" class="elsevierStylePara elsevierViewall">Based on these international studies&#44; the panel of experts considered the use of FRAX<span class="elsevierStyleSup">&#174;</span> without BMD as initial assessment of fracture risk&#46; When the risk calculated using the Spanish FRAX<span class="elsevierStyleSup">&#174;</span> without BMD&#44; for the principal fracture is &#8805;5&#37; it is advisable to perform DXA&#46;<a class="elsevierStyleCrossRef" href="#bib1165"><span class="elsevierStyleSup">34</span></a> Low risk patients are therefore not recommended to have DXA&#46;</p><p id="par0265" class="elsevierStylePara elsevierViewall">The panel also considered measuring in BMD&#44; regardless of age&#44; in the population which present with RF for fragility fractures such as&#58; previous fragility fracture&#44; women who begin treatment with aromatase inhibitors for breast cancer&#44;<a class="elsevierStyleCrossRef" href="#bib1170"><span class="elsevierStyleSup">35</span></a> males treated with androgen deprivation therapy for prostate cancer and patients treated with glucocorticoids&#46; The recent guideline of the <span class="elsevierStyleItalic">American College of Rheumatology</span> &#40;ACR&#41; for the prevention and treatment of OP using glucocorticoids recommends performing DXA in patients who start chronic treatment with glucocorticoids in the following cases&#58; &#40;1&#41; adults &#60;40<span class="elsevierStyleHsp" style=""></span>years of age when there is a background of fracture or high RF of fracture and &#40;2&#41; adults &#8805;40 years of age in all cases and calculate the FRAX<span class="elsevierStyleSup">&#174;</span> with BMD&#46;<a class="elsevierStyleCrossRef" href="#bib1175"><span class="elsevierStyleSup">36</span></a> the oncology guidelines and those of the <span class="elsevierStyleItalic">International Osteoporosis Foundation</span> &#40;IOF&#41; recommend DXA to decide whether to initiate treatment for OP in women receiving aromatase inhibitors<a class="elsevierStyleCrossRef" href="#bib1170"><span class="elsevierStyleSup">35</span></a> and in males in androgen deprivation therapy&#46;<a class="elsevierStyleCrossRef" href="#bib1180"><span class="elsevierStyleSup">37</span></a></p><p id="par0270" class="elsevierStylePara elsevierViewall">In cases of recent fracture due to fragility or treatment with high doses of glucocorticoids&#44; studies concluded that performing a DXA should not delay initiation of treatment to prevent new fractures&#46;<a class="elsevierStyleCrossRefs" href="#bib1055"><span class="elsevierStyleSup">12&#44;13</span></a></p><p id="par0275" class="elsevierStylePara elsevierViewall">Other patients who are eligible for DXA due to presenting with high OP and fragility fracture risks are those suffering from diseases associated with secondary OP&#44; such as chronic inflammatory arthropathies&#44; inflammatory bowel disease&#44; intestinal malabsorption syndromes&#44; chronic liver disease or advanced chronic kidney disease&#46; In these cases the panel considers BMD reasonable in order to establish prevention measures and appropriate treatment for each individual patient&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Trabecular Bone Score</span><p id="par0280" class="elsevierStylePara elsevierViewall">The <span class="elsevierStyleItalic">Trabecular Bone Score</span> &#40;TBS&#41; is an analysis of the bone texture obtained from the DXA which evaluates parameters related to the bone micro architecture of the lumbar spine and has good correlation with computerised tomography&#46;<a class="elsevierStyleCrossRefs" href="#bib1185"><span class="elsevierStyleSup">38&#44;39</span></a> Low TBS values are associated with an increased risk of primary osteoporotic fracture&#44; regardless of BMD&#46;<a class="elsevierStyleCrossRef" href="#bib1185"><span class="elsevierStyleSup">38</span></a> The combination of TBS and lumbar BMD increases the reduction of the risk of developing fractures&#46;<a class="elsevierStyleCrossRef" href="#bib1190"><span class="elsevierStyleSup">39</span></a> Furthermore&#44; the introduction of the TBS in the FRAX<span class="elsevierStyleSup">&#174;</span> algorithm enables a better prediction of the development of future fractures&#46;<a class="elsevierStyleCrossRefs" href="#bib1185"><span class="elsevierStyleSup">38&#44;40&#44;41</span></a> As a result&#44; according to studies&#44; the TBS could be an additional tool for the evaluation of fracture risk in patients with OP<a class="elsevierStyleCrossRefs" href="#bib1185"><span class="elsevierStyleSup">38&#8211;40</span></a> and in some causes of secondary OP &#40;diabetes&#44; hyperparathyroidism&#44; glucocorticoids&#41;&#46; However&#44; its usefulness in the monitorisation of the therapeutic response has not yet been established&#46;<a class="elsevierStyleCrossRef" href="#bib1185"><span class="elsevierStyleSup">38</span></a></p><p id="par0285" class="elsevierStylePara elsevierViewall">To sum up&#44; the panel of experts consider that although TBS could have several advantages in the evaluation of fracture risk&#44; further studies are required to recommend its use in clinical practice&#46;</p></span></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Analysis</span><p id="par0290" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">Recommendation&#58;</span><span class="elsevierStyleItalic">It is recommend that a basic analytical study be performed to rule out secondary causes of osteoporosis</span> &#40;RR&#58; &#8730;&#59; AL&#58; 100&#37;&#41;&#46;</p><p id="par0295" class="elsevierStylePara elsevierViewall">Basic laboratory tests to identify secondary OPs and make the differential diagnosis with other bone disease include<a class="elsevierStyleCrossRefs" href="#bib1145"><span class="elsevierStyleSup">30&#44;42&#44;43</span></a>&#58; haemogram&#44; serum calcium and phosphate tests&#44; alkaline phosphatase&#44; test&#44; proteingram&#44; albumin&#44; creatinine&#44; liver function tests&#44; calciuria and 25-hydroxy vitamin D tests&#46;</p><p id="par0300" class="elsevierStylePara elsevierViewall">Different scientific societies<a class="elsevierStyleCrossRefs" href="#bib1145"><span class="elsevierStyleSup">30&#44;42&#44;43</span></a> have produced documents with the following recommendations&#58;<ul class="elsevierStyleList" id="lis0020"><li class="elsevierStyleListItem" id="lsti0075"><span class="elsevierStyleLabel">&#8226;</span><p id="par0305" class="elsevierStylePara elsevierViewall">Additional tests will be carried out if there is suspicion of an associated condition&#58;<ul class="elsevierStyleList" id="lis0025"><li class="elsevierStyleListItem" id="lsti0080"><span class="elsevierStyleLabel">1&#46;</span><p id="par0310" class="elsevierStylePara elsevierViewall">PTH &#40;primary or secondary hyperparathyroidism&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0085"><span class="elsevierStyleLabel">2&#46;</span><p id="par0315" class="elsevierStylePara elsevierViewall">TSH &#40;hyperthyroidism&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0090"><span class="elsevierStyleLabel">3&#46;</span><p id="par0320" class="elsevierStylePara elsevierViewall">Immunoelectrophoresis &#40;myeloma&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0095"><span class="elsevierStyleLabel">4&#46;</span><p id="par0325" class="elsevierStylePara elsevierViewall">Antitransglutaminase antibodies &#40;celiac disease&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0100"><span class="elsevierStyleLabel">5&#46;</span><p id="par0330" class="elsevierStylePara elsevierViewall">Urinary cortisol &#40;Cushing&#39;s&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0105"><span class="elsevierStyleLabel">6&#46;</span><p id="par0335" class="elsevierStylePara elsevierViewall">Serum tryptase &#40;mastocytosis&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0110"><span class="elsevierStyleLabel">7&#46;</span><p id="par0340" class="elsevierStylePara elsevierViewall">Sexual hormone study &#40;young people&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0115"><span class="elsevierStyleLabel">8&#46;</span><p id="par0345" class="elsevierStylePara elsevierViewall">Genetic study &#40;imperfect osteogenesis&#44; hypophosphatase and others&#41;&#46;</p></li></ul></p></li></ul></p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Bone turnover markers</span><p id="par0350" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">Recommendation&#58;</span><span class="elsevierStyleItalic">The routine use of bone turnover markers has not been established&#46; However&#44; they could be considered in initial assessment and in follow-up of patients with osteoporosis</span> &#40;RR&#58; B&#59; AL&#58; 89&#37;&#41;&#46;</p><p id="par0355" class="elsevierStylePara elsevierViewall">The reductions of the greatest magnitude in markers of bone turnover &#40;MBT&#41; are significantly associated to more marked reductions in the non vertebral fracture risk&#44;<a class="elsevierStyleCrossRef" href="#bib1215"><span class="elsevierStyleSup">44</span></a> and the initial changes in a formation marker predict the efficacy of the bisphosphonates &#40;BP&#41; in the reduction of vertebral fracture risk&#46;<a class="elsevierStyleCrossRef" href="#bib1220"><span class="elsevierStyleSup">45</span></a> However&#44; there is not sufficient evidence to conclude that MBT are able to identify a reduction in risk fracture unequivocally&#46;<a class="elsevierStyleCrossRef" href="#bib1225"><span class="elsevierStyleSup">46</span></a></p><p id="par0360" class="elsevierStylePara elsevierViewall">The majority of GPC recommend the consideration of the use of MBT in the initial evaluation and in follow-up&#44; as an additional test&#46; In the initial evaluation&#44; the high levels may predict a faster loss of bone mass and a higher risk of fracture&#46; But their main indication is in follow-up&#44; since they can contribute to assessing treatment adherence and efficacy&#44; and also contribute to monitoring the duration of therapeutic holidays&#46;<a class="elsevierStyleCrossRefs" href="#bib1145"><span class="elsevierStyleSup">30&#44;42&#44;43&#44;47</span></a> The groups of international experts conclude that further research studies are required prior to making a recommendation based on the evidence&#46;<a class="elsevierStyleCrossRef" href="#bib1210"><span class="elsevierStyleSup">43</span></a> To conclude&#44; although the use of bone turnover markers has not been established as a routine&#44; the panel of experts suggest that they could provide additional information in the initial evaluation and in the patient follow-up with OP&#46;</p><p id="par0365" class="elsevierStylePara elsevierViewall">The two main serum references of MBT which are recommended to use by the IOF and the <span class="elsevierStyleItalic">International Federation of Clinical Chemistry and Laboratory Medicine</span> &#40;IFCC&#41; are the precollagen type I N-terminal propeptide &#40;PINP&#41;&#44; bone turnover marker and the Carboxyl-terminal telopeptide of type I collagen &#40;CTX&#41;&#44; a reabsorption marker&#46;<a class="elsevierStyleCrossRef" href="#bib1235"><span class="elsevierStyleSup">48</span></a></p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Vertebral fracture screening</span><p id="par0370" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">Recommendation&#58;</span><span class="elsevierStyleItalic">It is recommended that the presence of vertebral fractures be assessed in the patient with a high fracture risk or with osteoporosis&#44; when kyphosis or significant loss of height has presented and when there is back pain or low back pain of recent onset</span> &#40;RR&#58; D&#59; AL&#58; 100&#37;&#41;&#46;</p><p id="par0375" class="elsevierStylePara elsevierViewall">Chest and lumbar spine X-rays &#40;focused on T7 and L3&#44; respectively&#41; are the method of choice for diagnosis of a vertebral fracture&#46; A side projection is usually sufficient&#44; thus minimising the radiation the patient receives&#46;<a class="elsevierStyleCrossRef" href="#bib1240"><span class="elsevierStyleSup">49</span></a> These are useful in the initial evaluation of all patients diagnosed with OP when there is a significant loss of height or a change in relevant statics &#40;especially thoracic kyphosis&#41; and dorsolumbar pain of recent onset with or without a history of trauma<a class="elsevierStyleCrossRef" href="#bib1245"><span class="elsevierStyleSup">50</span></a> in a patient with a risk of OP or fracture&#46; Height loss which is significantly associated with the presence of vertebral fractures is not defined&#44; varying between 2<span class="elsevierStyleHsp" style=""></span>cm compared with measurement in previous years to 4<span class="elsevierStyleHsp" style=""></span>cm of historic loss since youth&#46;<a class="elsevierStyleCrossRefs" href="#bib1145"><span class="elsevierStyleSup">30&#44;51</span></a> The presence of a vertebral fracture&#44; the number of them and their degree of severity are highly relevant indicators of the risk of new vertebral fractures&#44; even those of the hip&#46;<a class="elsevierStyleCrossRef" href="#bib1255"><span class="elsevierStyleSup">52</span></a></p><p id="par0380" class="elsevierStylePara elsevierViewall">The panel of experts has thus considered that the presence of vertebral fractures should be assessed in the evaluation of the patient with OP or with a high risk of fracture when kyphosis or significant loss of height is present and there are clinical features of vertebral fracture&#46; Some DXA teams also use the <span class="elsevierStyleItalic">Vertebral Fracture Assessment</span> &#40;VFA&#41; to assess fractures&#46;</p></span></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Treatment</span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Non pharmacological therapies</span><p id="par0385" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">Recommendation&#58;</span><span class="elsevierStyleItalic">Included in the prevention of primary and secondary osteoporosis and fractures is the recommendation for a healthy lifestyle&#44; consisting of a balanced diet and regular physical exercise&#44; not smoking&#44; limiting alcohol consumption and using preventative measures against falls</span> &#40;RR&#58; &#8730;&#59; AL&#58; 100&#37;&#41;&#46;</p><p id="par0390" class="elsevierStylePara elsevierViewall">Several studies have concluded that the first step to the prevention of OP and the avoidance of fractures is to maintain healthy life habits&#46;<a class="elsevierStyleCrossRefs" href="#bib1260"><span class="elsevierStyleSup">53&#8211;57</span></a> Evidence suggests that exercise has a modest effect on reducing fractures and preventing falls&#46;<a class="elsevierStyleCrossRef" href="#bib1280"><span class="elsevierStyleSup">57</span></a><a class="elsevierStyleCrossRef" href="#tbl0025">Table 3</a> contains a summary of the most important measures to be taken into consideration&#46;</p><elsevierMultimedia ident="tbl0025"></elsevierMultimedia><p id="par0395" class="elsevierStylePara elsevierViewall">Studies show that the adoption of fall prevention measures&#44; in which exercise programmes and actions on environmental safety and minimisation of the use of drugs such as hypnotics&#44; diuretics&#44; antihypertensives and others which impair balance&#44; also contribute both to primary and secondary fragility fracture prevention&#46;<a class="elsevierStyleCrossRefs" href="#bib1280"><span class="elsevierStyleSup">57&#44;58</span></a></p><p id="par0400" class="elsevierStylePara elsevierViewall">In contrast&#44; exercises which require great effort or are abrupt and those which involve repeated flexion or twisting of the trunk and abdominals are ill-advised&#46;</p><p id="par0405" class="elsevierStylePara elsevierViewall">Regarding specific measures for the patient who has kyphosis&#44; studies have proven the effectiveness of exercise&#44; and training in muscular strength and balance&#46;<a class="elsevierStyleCrossRef" href="#bib1290"><span class="elsevierStyleSup">59</span></a></p><p id="par0410" class="elsevierStylePara elsevierViewall">The effectiveness of hip protectors in the prevention of fractures is inconclusive&#44; and adherence to their use is very low&#46;<a class="elsevierStyleCrossRef" href="#bib1295"><span class="elsevierStyleSup">60</span></a> Finally&#44; vibratory platforms have not demonstrated any consistent efficacy&#46;<a class="elsevierStyleCrossRef" href="#bib1300"><span class="elsevierStyleSup">61</span></a></p></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0155">Calcium and vitamin D</span><p id="par0415" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">Recommendation&#58;</span><span class="elsevierStyleItalic">It is recommended that a daily intake of calcium between 1000 and 1200</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">mg be taken and that it should mainly originate from a regular diet</span> &#40;RR&#58; D&#59; AL&#58; 100&#37;&#41;&#46;</p><p id="par0420" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">Recommendation&#58;</span><span class="elsevierStyleItalic">In the following cases a daily intake of 800</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">UI of vitamin D is recommended</span> &#40;RR&#58; D&#59; GA&#58; 100&#37;&#41;&#58;<ul class="elsevierStyleList" id="lis0030"><li class="elsevierStyleListItem" id="lsti0120"><span class="elsevierStyleLabel">1&#46;</span><p id="par0425" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Patients with osteoporosis&#46;</span></p></li><li class="elsevierStyleListItem" id="lsti0125"><span class="elsevierStyleLabel">2&#46;</span><p id="par0430" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">People over 65 years of age with fracture risk&#46;</span></p></li><li class="elsevierStyleListItem" id="lsti0130"><span class="elsevierStyleLabel">3&#46;</span><p id="par0435" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">People with a vitamin D deficit&#46;</span></p></li><li class="elsevierStyleListItem" id="lsti0135"><span class="elsevierStyleLabel">4&#46;</span><p id="par0440" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">People with limited exposure to the sun&#46;</span></p></li><li class="elsevierStyleListItem" id="lsti0140"><span class="elsevierStyleLabel">5&#46;</span><p id="par0445" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">People with an insufficient calcium intake &#40;under 700&#8211;800</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">mg daily&#41;&#46;</span></p></li></ul></p><p id="par0450" class="elsevierStylePara elsevierViewall">Studies coincide in the need to ensure an adequate provision of calcium as an essential feature in any OP treatment programme&#46;<a class="elsevierStyleCrossRef" href="#bib1230"><span class="elsevierStyleSup">47</span></a> Thus patients in pharmacological treatment for OP must use calcium and vitamin D supplements because practically all clinical trials which have demonstrated the efficacy of the antiosteoporotic drugs routinely include calcium supplements and cholecalciferol &#40;vitamin D<span class="elsevierStyleInf">3</span>&#41;&#46; When the calcium provided in the diet is insufficient&#44; it is recommended that calcium and vitamin D supplements be taken&#46; In postmenopausal women with OP the international expert groups advise an intake of 800&#8211;1&#46;200<span class="elsevierStyleHsp" style=""></span>mg&#47;of calcium per day and 800<span class="elsevierStyleHsp" style=""></span>UI&#47;of vitamin D per day&#46;<a class="elsevierStyleCrossRefs" href="#bib1305"><span class="elsevierStyleSup">62&#44;63</span></a></p><p id="par0455" class="elsevierStylePara elsevierViewall">In primary prevention a daily intake of calcium of 1000&#8211;1200<span class="elsevierStyleHsp" style=""></span>mg for women &#62;50 years of age and men &#62;70 years of age is advised&#44; preferably in the diet&#44; and 1000<span class="elsevierStyleHsp" style=""></span>mg&#47;of calcium per day in women &#60;50 years of age and men aged between 51 and 70&#46;</p><p id="par0460" class="elsevierStylePara elsevierViewall">Some foods are rich in calcium&#44; such as milk products &#40;milk&#44; cheese&#44; and yoghurt&#41; tinned oily fish&#44; beans and almonds&#46; A list of foods and an online calculator are available in the IOF website&#46;<a class="elsevierStyleCrossRefs" href="#bib1315"><span class="elsevierStyleSup">64&#44;65</span></a> if supplements are used&#44; the experts advise bearing in mind the optimum dose for calcium absorption which is situated in 500<span class="elsevierStyleHsp" style=""></span>mg of calcium&#44; and if larger doses are administered they should be spread over time&#46;<a class="elsevierStyleCrossRef" href="#bib1325"><span class="elsevierStyleSup">66</span></a></p><p id="par0465" class="elsevierStylePara elsevierViewall">With regard to the possible side effects of calcium supplements&#44; constipation and dyspeptic upsets are the most notable&#46; An increased risk of nephrolithiasis was demonstrated &#40;RR 1&#46;17&#41; in the <span class="elsevierStyleItalic">Women&#39;s Health Initiative</span><a class="elsevierStyleCrossRef" href="#bib1330"><span class="elsevierStyleSup">67</span></a> study&#44; attributed to a diet rich in calcium of the women studied&#46; However&#44; a systematic review concluded that the calcium supplements in OP treatment&#44; alone or in combination with other types of treatment&#44; did not significantly increase the risk of nephrolithiasis or renal colic&#46;<a class="elsevierStyleCrossRef" href="#bib1335"><span class="elsevierStyleSup">68</span></a> Controversy exists regarding the possible increased cardiovascular risk associated with calcium supplements&#44; particularly if the recommended maximum dose is exceeded&#46; The available evidence suggests that a total daily intake of calcium &#40;obtained by adding up dietary intake plus supplements&#41; under 2000<span class="elsevierStyleHsp" style=""></span>mg did not increase cardiovascular risk&#46;<a class="elsevierStyleCrossRefs" href="#bib1340"><span class="elsevierStyleSup">69&#44;70</span></a></p><p id="par0470" class="elsevierStylePara elsevierViewall">Regarding vitamin D&#44; in OP patients&#44; the conclusion reached by the experts is to maintain minimum serum concentrations of 25-hydroxy cholecalciferol &#40;calcidiol&#41; of 30<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#46; They therefore recommend measuring the calcidiol levels in patients with a risk of vitamin D deficiency and in patients with OP&#46; Given the essential role of sunlight as a source of vitamin D&#44; they advise an exposure to the sun of 10&#8211;15<span class="elsevierStyleHsp" style=""></span>min per day&#46;<a class="elsevierStyleCrossRefs" href="#bib1305"><span class="elsevierStyleSup">62&#44;63</span></a> When necessary&#59; they advise vitamin D supplements with a dose between 800 and 2000<span class="elsevierStyleHsp" style=""></span>UI&#47;day&#44; depending on baseline levels&#46; In patients with hepatopathies&#44; malabsorption syndromes&#44; treatment with anticonvulsives or other situations where the vitamin 25D hydroxylation may be compromised&#44; administration of the metabolite calcidiol is recommended&#46;</p><p id="par0475" class="elsevierStylePara elsevierViewall">Current scientific evidence enables us to state that neither the increase of dietary calcium nor the isolated intake of calcium supplements is able to protect against the presence of fractures&#46;<a class="elsevierStyleCrossRefs" href="#bib1350"><span class="elsevierStyleSup">71&#44;72</span></a> Vitamin D administered as a monotherapy is not effective in reducing fragility fractures either&#44; in non institutionalised elderly people&#46;<a class="elsevierStyleCrossRefs" href="#bib1355"><span class="elsevierStyleSup">72&#44;73</span></a> Calcium and vitamin D supplements have been show to be effective in the population &#62;65 years of age who reside in care homes&#44; reducing the risk of non vertebral fracture and marginally of hip fracture&#46;<a class="elsevierStyleCrossRefs" href="#bib1355"><span class="elsevierStyleSup">72&#44;74</span></a> This effect depends to a large extent on the vitamin D dose &#40;&#8805;800<span class="elsevierStyleHsp" style=""></span>UI daily&#41; and is more obvious at a greater age and with lower vitamin D levels&#46;<a class="elsevierStyleCrossRef" href="#bib1355"><span class="elsevierStyleSup">72</span></a> Calcium and vitamin D supplements do not reduce the risk of vertebral fracture&#46;<a class="elsevierStyleCrossRef" href="#bib1355"><span class="elsevierStyleSup">72</span></a></p><p id="par0480" class="elsevierStylePara elsevierViewall">The efficacy of calcium and vitamin D supplements in the non institutionalised population &#62;65 years of age &#40;residents in the community&#41; is questionable&#44; as evidenced by the high number required to treat &#40;NNT&#41; to prevent fracture in this low risk population group<a class="elsevierStyleCrossRef" href="#bib1365"><span class="elsevierStyleSup">74</span></a> and the results of a recent meta-analysis&#46;<a class="elsevierStyleCrossRef" href="#bib1370"><span class="elsevierStyleSup">75</span></a></p><p id="par0485" class="elsevierStylePara elsevierViewall">There are contradictory data on the efficacy of vitamin D in the prevention of falls&#46; Some results indicate that vitamin supplements&#44; with and without calcium&#44; would be effective in the prevention of falls&#44;<a class="elsevierStyleCrossRef" href="#bib1375"><span class="elsevierStyleSup">76</span></a> and especially in the elderly with vitamin D deficit&#46;<a class="elsevierStyleCrossRef" href="#bib1380"><span class="elsevierStyleSup">77</span></a> Other studies do not show this beneficial effect of vitamin D&#44;<a class="elsevierStyleCrossRef" href="#bib1385"><span class="elsevierStyleSup">78</span></a> and even the administration of annual high doses could increase the risk of falls&#46;<a class="elsevierStyleCrossRef" href="#bib1390"><span class="elsevierStyleSup">79</span></a></p></span><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0160">Treatment to prevent fractures</span><p id="par0490" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">Recommendation&#58;</span><span class="elsevierStyleItalic">It is recommended that pharmacological treatment be initiated to reduce the Risk of osteoporotic fracture in the following situations</span> &#40;RR&#58; &#8730;&#41;&#58;<ul class="elsevierStyleList" id="lis0035"><li class="elsevierStyleListItem" id="lsti0145"><span class="elsevierStyleLabel">1&#46;</span><p id="par0495" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Fragility fracture of vertebra or hip in patients &#62;50 years of age &#40;AL&#58; 100&#37;&#41;</span>&#46;</p></li><li class="elsevierStyleListItem" id="lsti0150"><span class="elsevierStyleLabel">2&#46;</span><p id="par0500" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Other fragility fractures in patients &#62;50 years of age and with low bone mass &#40;T-score &#60;&#8722;1 S&#41; &#40;AL&#58; 89&#37;&#41;</span>&#46;</p></li><li class="elsevierStyleListItem" id="lsti0155"><span class="elsevierStyleLabel">3&#46;</span><p id="par0505" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">OP defined by T-score &#8804;&#8722;2&#46;5 SD in spine&#44; femoral neck or total hip&#44; always evaluating age&#44; BMD figures and other risk factors &#40;AL&#58; 100&#37;&#41;</span>&#46;</p></li><li class="elsevierStyleListItem" id="lsti0160"><span class="elsevierStyleLabel">4&#46;</span><p id="par0510" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Patients with a high hip fracture risk according to FRAX</span><span class="elsevierStyleSup"><span class="elsevierStyleItalic">&#174;</span></span><span class="elsevierStyleItalic">with BMD &#8805;3&#37; &#40;AL&#58; 100&#37;&#41;</span>&#46;</p></li><li class="elsevierStyleListItem" id="lsti0165"><span class="elsevierStyleLabel">5&#46;</span><p id="par0515" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Males in androgen deprivation treatment and T-score &#8804;&#8722;2&#46;5 SD &#40;AL&#58; 100&#37;&#41;</span>&#46;</p></li><li class="elsevierStyleListItem" id="lsti0170"><span class="elsevierStyleLabel">6&#46;</span><p id="par0520" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Women in treatment with aromatase inhibitors and T-score &#8804;&#8722;2 or with a T-score &#60;&#8722;1&#46;5 SD and an additional risk factor&#44; or with &#8805;2 risk factors without BMD &#40;AL&#58; 100&#37;&#41;</span>&#46;</p></li><li class="elsevierStyleListItem" id="lsti0175"><span class="elsevierStyleLabel">7&#46;</span><p id="par0525" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Patients in treatment with glucocorticoids and&#58; &#40;a&#41; initial dose &#8805;30</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">mg&#47;day of prednisone&#59; &#40;b&#41; postmenopausal women and men &#62;50 years of age with a dose of &#8805;5 mg&#47;day and previous fragility fracture or T-score &#8804;&#8722;1&#46;5 SD or high risk of fracture&#58; FRAX</span><span class="elsevierStyleSup"><span class="elsevierStyleItalic">&#174;</span></span><span class="elsevierStyleItalic">for hip &#8805;3&#37; or for primary fracture &#8805;10&#37; without BMD or &#8805;7&#46;5&#37; with BMD &#40;AL&#58; 78&#37;&#41;</span>&#46;</p></li></ul></p><p id="par0530" class="elsevierStylePara elsevierViewall">The drugs used for the treatment of OP have been shown to be more effective in patients with a high risk of fracture and in those with an existing fracture or with a <span class="elsevierStyleItalic">T</span>-score &#8804;&#8722;2&#46;5 SD&#46;<a class="elsevierStyleCrossRef" href="#bib1395"><span class="elsevierStyleSup">80</span></a></p><p id="par0535" class="elsevierStylePara elsevierViewall">The NOF recommendations and those of other expert groups support the use of FRAX<span class="elsevierStyleSup">&#174;</span> in selecting candidates for treatment&#44; including cases without OP using DXA&#46;<a class="elsevierStyleCrossRefs" href="#bib1145"><span class="elsevierStyleSup">30&#44;80</span></a></p><p id="par0540" class="elsevierStylePara elsevierViewall">The panel thus considers that treatment is indicated in patients with fragility fracture&#44; OP from DXA <span class="elsevierStyleItalic">T</span>-score &#8804;&#8722;2&#46;5 SD&#44; high fracture risk &#40;FRAX<span class="elsevierStyleSup">&#174;</span> for hip fracture with BMD &#8805;3&#37;&#41;<a class="elsevierStyleCrossRefs" href="#bib1110"><span class="elsevierStyleSup">23&#44;34</span></a> and in sub-groups of patients who take glucocorticoids&#44; aromatase inhibitors<a class="elsevierStyleCrossRef" href="#bib1170"><span class="elsevierStyleSup">35</span></a> or antiandrogens&#46;<a class="elsevierStyleCrossRef" href="#bib1180"><span class="elsevierStyleSup">37</span></a> The specific circumstances where osteoporotic antifracture treatment should be assessed is commented upon in detail in other sections&#46;</p><p id="par0545" class="elsevierStylePara elsevierViewall">Regarding patients with fragility fractures&#44; the NOF recommends treating all hip and vertebra fractures&#44; whilst the other fractures would be treated depending on the results of the DXA and the risk of new fractures calculated using the FRAX<span class="elsevierStyleSup">&#174;</span>&#46;<a class="elsevierStyleCrossRef" href="#bib1145"><span class="elsevierStyleSup">30</span></a></p><p id="par0550" class="elsevierStylePara elsevierViewall">Regarding the evaluation of treatment based on the DXA outcome with a <span class="elsevierStyleItalic">T</span>-score &#8804;&#8722;2&#46;5 SD&#44; the panel wishes to highlight that in these cases clinical risk factors and the FRAX<span class="elsevierStyleSup">&#174;</span> should also be considered when decision are to be taken&#46;</p><p id="par0555" class="elsevierStylePara elsevierViewall">Prophylaxis and treatment of OP induced by glucocorticoids are dealt with in a separate section&#46;</p><p id="par0560" class="elsevierStylePara elsevierViewall">Several international guidelines&#44; including those on oncology&#44; advise that treatment be indicated for OP in women who receive aromatase inhibitors and have a <span class="elsevierStyleItalic">T</span>-score below or equal to &#8722;2 SD or with a <span class="elsevierStyleItalic">T</span>-score &#60;&#8722;1&#46;5 SD with an additional risk factor&#44; or with &#8805;2 risk factors without BMD&#46;<a class="elsevierStyleCrossRef" href="#bib1170"><span class="elsevierStyleSup">35</span></a> For men in androgen deprivation therapy&#44; the IOF fixes the threshold for treating OP in a <span class="elsevierStyleItalic">T</span>-score of &#8722;2&#46;5 SD or a raised fracture risk by FRAX<span class="elsevierStyleSup">&#174;</span><a class="elsevierStyleCrossRef" href="#bib1180"><span class="elsevierStyleSup">37</span></a> &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0105" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0165">Antifracture treatment choice</span><p id="par0565" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">Recommendation&#58;</span><span class="elsevierStyleItalic">When selecting treatment&#44; among other factors&#44; it is recommended to take the following into consideration</span> &#40;RR&#58; &#8730;&#59; AL&#58; 100&#37;&#41;&#58;<ul class="elsevierStyleList" id="lis0040"><li class="elsevierStyleListItem" id="lsti0180"><span class="elsevierStyleLabel">1&#46;</span><p id="par0570" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">The efficacy and safety of the drugs&#46;</span></p></li><li class="elsevierStyleListItem" id="lsti0185"><span class="elsevierStyleLabel">2&#46;</span><p id="par0575" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Cost-effectiveness ratio&#46;</span></p></li><li class="elsevierStyleListItem" id="lsti0190"><span class="elsevierStyleLabel">3&#46;</span><p id="par0580" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">The value of the BMD&#46;</span></p></li><li class="elsevierStyleListItem" id="lsti0195"><span class="elsevierStyleLabel">4&#46;</span><p id="par0585" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">The presence of fractures&#44; particularly vertebral or multiple fractures due to fragility&#46;</span></p></li><li class="elsevierStyleListItem" id="lsti0200"><span class="elsevierStyleLabel">5&#46;</span><p id="par0590" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Treatments prior to this and adherence to them&#46;</span></p></li><li class="elsevierStyleListItem" id="lsti0205"><span class="elsevierStyleLabel">6&#46;</span><p id="par0595" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Age&#46;</span></p></li><li class="elsevierStyleListItem" id="lsti0210"><span class="elsevierStyleLabel">7&#46;</span><p id="par0600" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Comorbidities and polymedication&#46;</span></p></li><li class="elsevierStyleListItem" id="lsti0215"><span class="elsevierStyleLabel">8&#46;</span><p id="par0605" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Limitations for oral administration&#46;</span></p></li></ul></p><p id="par0610" class="elsevierStylePara elsevierViewall">The final aim of OP treatment is the prevention of fractures&#46; <a class="elsevierStyleCrossRef" href="#tbl0025">Table 3</a> contains the efficacy in primary and secondary prevention of vertebral and non vertebral fractures of the drugs used in Spain&#46;<a class="elsevierStyleCrossRefs" href="#bib1400"><span class="elsevierStyleSup">81&#8211;94</span></a></p><p id="par0615" class="elsevierStylePara elsevierViewall">In the main studies conducted with drugs in patients who only had osteopenia without prevalent fracture &#40;primary prevention&#41; no fracture reduction occurred in primary outcome&#46;</p><p id="par0620" class="elsevierStylePara elsevierViewall">In primary fracture prevention in patients with OP&#44; the drugs which demonstrated a reduction of vertebral fracture were&#58; alendronic acid&#44; zoledronic acid&#44; raloxifene&#44; bazedoxifene and denosumab&#44; whilst denosumab also reduced non vertebral fracture and hip fracture in this group&#46;</p><p id="par0625" class="elsevierStylePara elsevierViewall">In patients with OP and vertebral fracture&#44; alendronic acid&#44; risedronic acid and zoledronic acid reduced new vertebral&#44; non vertebral and hip fractures&#44; whilst teriparatide reduced vertebral and non vertebral fractures and denosumab reduced vertebral fractures&#46; For their part&#44; ibandronic acid&#44; raloxifene and bazedoxifene reduced vertebral fractures in patients with previous fracutre&#46;<a class="elsevierStyleCrossRefs" href="#bib1400"><span class="elsevierStyleSup">81&#8211;94</span></a> With regard to forearm fractures&#44; alendronic acid demonstrated a significant reduction of new wrist fractures in meta-analysis in patients with previous vertebral fracture&#46;<a class="elsevierStyleCrossRef" href="#bib1400"><span class="elsevierStyleSup">81</span></a></p><p id="par0630" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRefs" href="#tbl0030">Tables 4&#8211;7</a> contain details of the risk reduction for different fractures in the published studies&#46;<a class="elsevierStyleCrossRefs" href="#bib1410"><span class="elsevierStyleSup">83&#8211;94</span></a></p><elsevierMultimedia ident="tbl0030"></elsevierMultimedia><elsevierMultimedia ident="tbl0035"></elsevierMultimedia><elsevierMultimedia ident="tbl0040"></elsevierMultimedia><elsevierMultimedia ident="tbl0045"></elsevierMultimedia><p id="par0635" class="elsevierStylePara elsevierViewall">In patients with at least two moderate vertebral fractures or at least one severe fracture teriparatide was significantly more effective than risedronic acid for reducing new morphometric and clinical vertebral fractures after 24 months of treatment&#46; There were no significant differences in the rate of new non vertebral fractures&#46;<a class="elsevierStyleCrossRef" href="#bib1470"><span class="elsevierStyleSup">95</span></a></p><p id="par0640" class="elsevierStylePara elsevierViewall">Strontium renalate has not been included in these recommendations because its production has been suspended&#44; nor calcitonin&#44; because of the limitation its technical record has in treatment indication and duration&#46; However&#44; therapy with oestrogens reduces vertebral and hip fractures&#44; but is currently not used due to its poor risk&#47;benefit profile and because safer treatments exist&#46;</p><p id="par0645" class="elsevierStylePara elsevierViewall">The following aspects have to be taken into consideration when integrating trial outcomes into clinical practice&#58; &#40;1&#41; the patient profile included is a postmenopausal woman with a high baseline risk due to age and the presence of previous fractures&#59; &#40;2&#41; the populations of the trials are different to one another&#44; and therefore may not be directly compared&#59; &#40;3&#41; the studies were conducted with calcium and&#47;or vitamin D supplements and &#40;4&#41; real treatment adherence is lower than that reported in the trials&#46; Moreover&#44; treatment should be individualised according to the circumstances of each patient&#46;</p><p id="par0650" class="elsevierStylePara elsevierViewall">Another aspect to take into account is the cost&#47;effectiveness ratio of treatment&#46; The studies undertaken in other countries fix the threshold of FRAX<span class="elsevierStyleSup">&#174;</span> for primary fracture&#44; so that the cost-effectiveness of the treatment is 8&#46;8&#37; &#40;Portugal&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib1475"><span class="elsevierStyleSup">96</span></a> 13&#46;8&#37; &#40;Switzerland&#41;<a class="elsevierStyleCrossRef" href="#bib1480"><span class="elsevierStyleSup">97</span></a> and 10&#37;&#8211;15&#37; &#40;Greece&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib1485"><span class="elsevierStyleSup">98</span></a> For estimation the cost of alendronic acid was considered &#40;Portugal and Switzerland&#41; and the average cost of treatment for OP &#40;Greece&#41;&#46; When drugs other than alendronic acid were considered&#44; the FRAX<span class="elsevierStyleSup">&#174;</span> threshold for cost effectiveness was higher&#46;<a class="elsevierStyleCrossRefs" href="#bib1475"><span class="elsevierStyleSup">96&#8211;98</span></a> Despite no cost-effectiveness studies existing for Spain based on fracture risk&#44; the panel of experts advised taking into account BP as first line option in OP treatment&#46;</p><p id="par0655" class="elsevierStylePara elsevierViewall">The panel of experts therefore consider that when choosing treatment to prevent fractures the efficacy and safety of the drugs&#44; cost-effectiveness ratio&#44; BMD figures&#44; and presence of previous features &#40;location&#44; number and time passed since fracture&#41; and oral administration route limitations should be contemplated&#46; Other factors which also were to be taken into account were previous treatments and adherence to them&#44; co morbidities and patient preferences&#46; Thus&#44; in patients with several fractures&#44; oral intolerance&#44; dementia&#44; malabsorption and poor adherence&#44; parenteral therapy could be considered&#46;</p></span><span id="sec0110" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0170">Sequential and combined therapy</span><p id="par0660" class="elsevierStylePara elsevierViewall">The risk of long-term complications in OP treatments<a class="elsevierStyleCrossRefs" href="#bib1490"><span class="elsevierStyleSup">99&#8211;101</span></a> and the increase in the risk of fracture after their suspension<a class="elsevierStyleCrossRefs" href="#bib1505"><span class="elsevierStyleSup">102&#44;103</span></a> often obliges physicians to put forward a sequential treatment strategy&#46;</p><p id="par0665" class="elsevierStylePara elsevierViewall">Although there are currently no outcomes on fracture reduction with sequential treatment&#44;<a class="elsevierStyleCrossRefs" href="#bib1515"><span class="elsevierStyleSup">104&#44;105</span></a> the bone forming sequence &#40;teriparatide&#41; followed by antiresorptive sequence &#40;denosumab or BP&#41;<a class="elsevierStyleCrossRefs" href="#bib1515"><span class="elsevierStyleSup">104&#8211;106</span></a> is the most effective in terms of gaining BMD&#46; Teriparatide followed by denosumab appears to be more effective than teriparatide followed by BP&#46;<a class="elsevierStyleCrossRef" href="#bib1530"><span class="elsevierStyleSup">107</span></a></p><p id="par0670" class="elsevierStylePara elsevierViewall">The administration of teriparatide after an antiresorptive drug is also effective&#44; although its anabolic effect may slow down &#40;less change in bone markers and lower increase of BMD&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib1535"><span class="elsevierStyleSup">108</span></a> and if administered after denosumab it has been described as a loss of initial BMD in the hip&#46;<a class="elsevierStyleCrossRef" href="#bib1525"><span class="elsevierStyleSup">106</span></a> Sequential treatment with romosozumab followed by an antiresorptive drug is dealt with in the section relating to new treatments&#46;</p><p id="par0675" class="elsevierStylePara elsevierViewall">Little information exists on the use of one antiresorptive drug followed by another&#44; especially if the first was administered for years&#46; A review of 11 prospective studies of patients previously treated with alendronic acid or risedronic acid showed that the change to ranelate from strontium or denosumab achieved an additional increase in BMD&#46;<a class="elsevierStyleCrossRef" href="#bib1540"><span class="elsevierStyleSup">109</span></a> However&#44; no data were available on fracture reduction either&#46;<a class="elsevierStyleCrossRef" href="#bib1540"><span class="elsevierStyleSup">109</span></a> In one study denosumab showed increases in BMD in patients who had been treated with zoledronic acid&#46;<a class="elsevierStyleCrossRef" href="#bib1545"><span class="elsevierStyleSup">110</span></a></p><p id="par0680" class="elsevierStylePara elsevierViewall">There are studies which show greater efficacy in combined therapy &#40;bone formation and antiresorptive&#41; compared with monotherapy&#46; The combination of zoledronic acid and teriparatide has been associated with a higher increase in femoral BMD one year after treatment compared with teriparatide in monotherapy&#46;<a class="elsevierStyleCrossRefs" href="#bib1515"><span class="elsevierStyleSup">104&#44;111</span></a> The combination of denosumab and teriparatide has been associated with a greater increase in lumbar spine and proximal femur BMD&#44; compared with both drugs in monotherapy&#46;<a class="elsevierStyleCrossRef" href="#bib1555"><span class="elsevierStyleSup">112</span></a> Notwithstanding&#44; there is no evidence of reduction of fractures with these combinations&#46; After a review of the literature&#44; the panel concluded that combined &#40;bone formation and antiresorptive&#41; treatment did not appear to be an option to recommend in general&#44; although its use could be justified in highly selected serious cases of OP&#46;</p></span><span id="sec0115" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0175">Treatment duration</span><p id="par0685" class="elsevierStylePara elsevierViewall">OP is a chronic disease&#44; and treatment must therefore be maintained indefinitely or at least for several years&#46; However&#44; there is no recommended maximum treatment for each drug used&#46;<a class="elsevierStyleCrossRefs" href="#bib1205"><span class="elsevierStyleSup">42&#44;100</span></a></p><p id="par0690" class="elsevierStylePara elsevierViewall">The antiresorptive drugs &#40;selective oestrogen receptor modulators&#44; SERM&#44; BP and denosumab&#41; generally reduce fracture risk from 12 to 18<span class="elsevierStyleHsp" style=""></span>months<a class="elsevierStyleCrossRefs" href="#bib1435"><span class="elsevierStyleSup">88&#44;91&#44;113</span></a> and have no maximum approved duration&#46;</p><p id="par0695" class="elsevierStylePara elsevierViewall">In the case of BP&#44; its efficacy&#44; in terms of BMD and fracture risk reduction is maintained for at least 3 years of treatment&#46;<a class="elsevierStyleCrossRefs" href="#bib1565"><span class="elsevierStyleSup">114&#44;115</span></a> Some studies show that from the 4th or 5th year BMD slightly rises or remains stable and the risk of some complications increases so that after 5 years of treatment with oral BP or 3 years with zoledronic acid it is advisable to evaluate the risk&#47;benefit of continuing with treatment&#46;<a class="elsevierStyleCrossRef" href="#bib1575"><span class="elsevierStyleSup">116</span></a> The Groups of experts agrees in recommending maintaining treatment &#40;up to 10 years for oral BP or up to 6 years for zoledronic acid&#41; in patients with a high fracture risk &#40;fractures prior or during treatment&#44; age &#62;75 years or <span class="elsevierStyleItalic">T</span>-score &#8804;&#8722;2&#46;5 SD in femoral neck or total hip&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib1205"><span class="elsevierStyleSup">42&#44;100&#44;117&#44;118</span></a></p><p id="par0700" class="elsevierStylePara elsevierViewall">Denosumab produces a progressive increase of BMD for at least 10 years of treatment&#44; maintaining its ant fracture efficacy over time&#46;<a class="elsevierStyleCrossRef" href="#bib1590"><span class="elsevierStyleSup">119</span></a> Although there is no consensus regarding the duration of this treatment&#44; some authors indicate that it could be established according to a predefined objective &#40;treat to target strategy&#41;&#44; i&#46;e&#46; after reaching a certain BMD value&#46;<a class="elsevierStyleCrossRef" href="#bib1595"><span class="elsevierStyleSup">120</span></a> however&#44; they should not suspend treatment with denosumab without establishing other treatment for OP &#40;see section &#8220;Suspension or discontinuation of treatment&#8221;&#41;&#46;</p><p id="par0705" class="elsevierStylePara elsevierViewall">Although data exist on efficacy and safety of SERM &#40;raloxifene and bazedoxifene&#41; up to 8 years&#44; maximum duration of the treatment is conditioned by the risk of complications such as thromboembolism&#44; which is more frequent in patients over 70&#46;<a class="elsevierStyleCrossRef" href="#bib1600"><span class="elsevierStyleSup">121</span></a></p><p id="par0710" class="elsevierStylePara elsevierViewall">Regarding patients who receive glucocorticoids&#44; aromatase inhibitors or androgen deprivation therapy&#44; the panel of experts consider that antiresorptive treatment should be maintained at least whilst the patient receives the inductor drug of OP &#40;see &#8220;Osteoporosis by glucocorticoids&#8221;&#41;&#46;</p><p id="par0715" class="elsevierStylePara elsevierViewall">Teriparatide has been shown to reduce the risk of fracture after 6&#8211;12<span class="elsevierStyleHsp" style=""></span>months of treatment initiation&#46; However&#44; to achieve maximum efficacy&#44; both in trabecular and cortical bones&#44; different groups of experts agree that it is recommendable to maintain it for 2 years&#44; which is the maximum period approved&#46;<a class="elsevierStyleCrossRefs" href="#bib1205"><span class="elsevierStyleSup">42&#44;100&#44;108</span></a></p><span id="sec0120" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0180">Treatment suspension or discontinuation</span><p id="par0720" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">Recommendation&#58;</span><span class="elsevierStyleItalic">It is recommended that fracture risk be reassessed after 5 years of treatment with oral bisphosphonates or after 3 years of treatment with zoledronic acid</span> &#40;RR&#58; D&#59; AL&#58; 100&#37;&#41;&#46;</p><p id="par0725" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">Recommendation&#58;</span><span class="elsevierStyleItalic">When treatment with denosumab it suspended an alternative treatment for osteoporosis should be contemplated</span> &#40;RR&#58; D&#59; AL&#58; 100&#37;&#41;&#46;</p><p id="par0730" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">Recommendation&#58;</span><span class="elsevierStyleItalic">In patients with high fracture risks like those with a previous fragility fracture&#44; or with a T-score of proximal femur &#60;&#8722;2&#46;5 SD&#44; it is not recommended to discontinue osteoporosis treatment</span> &#40;RR&#58; D&#59; AL&#58; 89&#37;&#41;&#46;</p><p id="par0735" class="elsevierStylePara elsevierViewall">OP treatment implies that the patient will receive medication for years&#44; although in some cases it is possible to have interruptions&#46; The so-called &#8220;therapeutic holidays&#8221; are a temporary suspension of treatment with BP to reduce the presence of adverse effects&#44; because they accumulate in the bone tissue and maintain their effect even years after having been suspended&#46;<a class="elsevierStyleCrossRefs" href="#bib1570"><span class="elsevierStyleSup">115&#44;122&#8211;124</span></a> This residual effect is not observed with other drugs such as SERM&#44; denosumab or teriparatide&#46;</p><p id="par0740" class="elsevierStylePara elsevierViewall">Although the decision to discontinue treatment with BP must be individualised&#44; the consensus of experts advise reassessing treatment in patients with low fracture risk and who have not presented with incident fractures after 5 years of treatment with oral BP or 3 years with zoledronic acid&#46;<a class="elsevierStyleCrossRef" href="#bib1495"><span class="elsevierStyleSup">100</span></a> The duration of this discontinuation is unknown and has been calculated to be between 2 and 3<span class="elsevierStyleHsp" style=""></span>years&#44; depending on the BP used&#46;<a class="elsevierStyleCrossRefs" href="#bib1495"><span class="elsevierStyleSup">100&#44;125</span></a> Although there is little evidence&#44; the changes in BMD and bone turnover markers could help with decision-making&#46;<a class="elsevierStyleCrossRef" href="#bib1495"><span class="elsevierStyleSup">100</span></a></p><p id="par0745" class="elsevierStylePara elsevierViewall">The majority of international guidelines advise not to suspend treatment with BP in high fracture risk patients&#44; like those with previous fragility fractures&#44; a low <span class="elsevierStyleItalic">T</span>-score in hip or in those who present with a fragility fracture during treatment&#46;<a class="elsevierStyleCrossRefs" href="#bib1495"><span class="elsevierStyleSup">100&#44;126&#44;127</span></a> Regarding the value of the BMD capable of predicting a high fracture risk on suspending treatment&#44; the post hoc analysis of the FLEX and HORIZON studies state this as a femoral <span class="elsevierStyleItalic">T</span>-score &#60;&#8722;2&#46;5 SD&#46;<a class="elsevierStyleCrossRefs" href="#bib1605"><span class="elsevierStyleSup">122&#44;124</span></a> If treatment with BP is prolonged&#44; it seems reasonable to reassess after 5 years of treatment with oral BP or 3 years with zoledronic acid&#46;<a class="elsevierStyleCrossRefs" href="#bib1495"><span class="elsevierStyleSup">100&#44;126</span></a></p><p id="par0750" class="elsevierStylePara elsevierViewall">According to different scientific societies and groups of experts&#44; the concept of treatment suspension should not be applied to other drugs such as denosumab&#44; since its removal may lead to an increase in bone remodelling&#44; with a decrease in BMD and an increase in fracture risk&#44; including multiple fractures after its suspension&#46;<a class="elsevierStyleCrossRefs" href="#bib1630"><span class="elsevierStyleSup">127&#8211;130</span></a> For this reason&#44; they concluded that if it is decided to suspend treatment for any reason with denosumab&#44; an alternative treatment should always be considered&#46;<a class="elsevierStyleCrossRef" href="#bib1635"><span class="elsevierStyleSup">128</span></a> The panel of experts&#44; despite little evidence regarding the consequences of suspension of denosumab and its alternative treatment efficacy&#44; recommend that when treatment is suspended with denosumab an alternative OP treatment be sought&#46;</p></span><span id="sec0125" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0185">Follow-up&#44; monitorisation and adherence</span><p id="par0755" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">Recommendation&#58;</span><span class="elsevierStyleItalic">Periodical clinical evaluation for confirming compliance and efficacy of treatment&#44; incidence of fractures and the possible presence of adverse effects is recommended</span> &#40;RR&#58; &#8730;&#59; AL&#58; 100&#37;&#41;&#46;</p><span id="sec0130" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0190">Adherence</span><p id="par0760" class="elsevierStylePara elsevierViewall">Low OP treatment adherence is a frequent problem&#44; after 12 months of treatment less than half of the patients stick to the therapy they were prescribed&#46;<a class="elsevierStyleCrossRef" href="#bib1650"><span class="elsevierStyleSup">131</span></a> Low adherence is also associated with an increased fracture risk&#46;<a class="elsevierStyleCrossRef" href="#bib1655"><span class="elsevierStyleSup">132</span></a></p><p id="par0765" class="elsevierStylePara elsevierViewall">The efficacy of different measures has been studied to improve adherence&#44; such as telephone calls or meetings with patients&#44; but none of them appear to have been truly effective&#46;<a class="elsevierStyleCrossRef" href="#bib1660"><span class="elsevierStyleSup">133</span></a> In a systematic review of 20 studies it was observed that the simplification of posology&#44; electronic prescription and the intervention of the pharmacist improved adherence or persistence of OP treatment&#46; Patient education has demonstrated its effectiveness in several studies&#44; but not in all of them&#44; whilst monitorisation and supervision had no significant impact on adherence&#46;<a class="elsevierStyleCrossRef" href="#bib1665"><span class="elsevierStyleSup">134</span></a> However&#44; the <span class="elsevierStyleItalic">Fracture Liaison Service</span> &#40;FLS&#41; units for secondary fracture prevention reported an adherence &#62;70&#37; at 1&#8211;2 years&#44; which was related partly to the educational efforts made by the nurse&#46;<a class="elsevierStyleCrossRefs" href="#bib1670"><span class="elsevierStyleSup">135&#44;136</span></a></p><p id="par0770" class="elsevierStylePara elsevierViewall">MBT could help with follow-up and adherence&#46; The IOF and <span class="elsevierStyleItalic">European Calcified Tissue Society</span> &#40;ECTS&#41;&#44; in a workgroup for analysing the usefulness of the MBT in oral BP adherence&#44; recommended measuring PINP and CTX at the beginning of treatment and after 3 months&#44; to verify whether there was a greater reduction to the minimum significant change of the MBT&#46;<a class="elsevierStyleCrossRef" href="#bib1680"><span class="elsevierStyleSup">137</span></a> The same workgroup considered a significant change to be a reduction that was higher than 38&#37; for PINP and above 56&#37; for CTX&#44; whilst absence of change suggested the need for reassessment to identify problems with treatment&#44; mainly low adherence&#46;<a class="elsevierStyleCrossRef" href="#bib1680"><span class="elsevierStyleSup">137</span></a> In one meta-analysis of 6 studies which assessed the efficacy of the MBT to improve treatment adherence&#44; compliance was a high average&#44; and it was difficult to assess the repercussion of the act of informing of the outcomes of the MBT&#46;<a class="elsevierStyleCrossRef" href="#bib1225"><span class="elsevierStyleSup">46</span></a> In the meta-analysis one study stood out where higher persistence was observed if the patient was informed of their response to treatment &#40;HR for discontinuation 0&#46;71&#59; 95&#37; CI&#58; &#46;53&#8211;&#46;95&#41;&#44; whilst informing of the poor response to the drug reduced it &#40;HR for discontinuation 2&#46;22&#59; 95&#37; CI&#58; 1&#46;27&#8211;3&#46;89&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib1685"><span class="elsevierStyleSup">138</span></a> The reinforcement using the outcomes of the MBT thus had an influence on persistence&#44; depending on the response of the MBT&#46;</p></span></span></span><span id="sec0135" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0195">Monitorisation</span><p id="par0775" class="elsevierStylePara elsevierViewall">OP treatment monitorisation includes the analytical determinations and the DXA&#44; as well as asking the patient about new fractures&#46; Several studies conclude that the bone remodelling markers could be useful for early monitoring of compliance and response to treatment&#44;<a class="elsevierStyleCrossRef" href="#bib1690"><span class="elsevierStyleSup">139</span></a> but the panel of experts consider that they cannot recommend their systematic determination in patient follow-up&#46; The panel recommends monitoring the response to treatment through central DXA&#44; bearing in mind patient characteristics&#46;</p><p id="par0780" class="elsevierStylePara elsevierViewall">There are no controlled&#44; good quality studies on the frequency with which measurement of the BMD should be repeated during treatment&#46;<a class="elsevierStyleCrossRef" href="#bib1695"><span class="elsevierStyleSup">140</span></a> Possible variation in BMD with current treatments is slow to occur and usually of little magnitude&#46; Given the risk of DXA measurement error&#44; international experts concluded that measurement should be made when the expected change is equal to or higher than the minimum significant difference&#46;<a class="elsevierStyleCrossRef" href="#bib1155"><span class="elsevierStyleSup">32</span></a> For this reason&#44; in general&#44; it is not advised to repeat measurement of the BMD before 2&#8211;3 years&#46;<a class="elsevierStyleCrossRefs" href="#bib1020"><span class="elsevierStyleSup">5&#44;141</span></a> Other guidelines advise lengthening this time period to 3 years for zoledronic acidy and up to 5 years for oral BP&#46;<a class="elsevierStyleCrossRefs" href="#bib1625"><span class="elsevierStyleSup">126&#44;142&#44;143</span></a> In situations of high fracture risk&#44;<a class="elsevierStyleCrossRef" href="#bib1020"><span class="elsevierStyleSup">5</span></a> in treatment with high doses of glucocorticoids or when there is a suspicion of failure in therapy&#44; such as when a new fracture occurs&#44; the period for repeating DXA may be shortened&#46;<a class="elsevierStyleCrossRef" href="#bib1715"><span class="elsevierStyleSup">144</span></a> The aim is to detect the patients who&#44; despite treatment&#44; suffer from a significant drop in BMD&#46; It is also advised to carry out a DXA when planning temporary suspension of the drug for &#8220;therapeutic holidays&#8221;&#46;<a class="elsevierStyleCrossRef" href="#bib1615"><span class="elsevierStyleSup">124</span></a> Although the greatest changes in BMD are detected in the lumbar spine&#44; it is useful to also monitor the hip&#44; as it is less dependent on artefacts impacted by degenerative changes&#46;</p><p id="par0785" class="elsevierStylePara elsevierViewall">Several authors propose using a treat to target strategy in OP where the objectives would be to reach a certain value of the <span class="elsevierStyleItalic">T</span>-score &#40;for example&#44; <span class="elsevierStyleItalic">T</span>-score&#58; &#8722;2&#46;5 SD&#41; or BMD&#46; If this occurred&#44; monitorisation of the BMD would enable the knowledge of whether the therapeutic aim had been reached&#46; However&#44; not all drugs lead to an improvement of BMD proportional to the reduction of fracture risk&#44; and the real value of this strategy in clinical practice is also yet to be defined&#46;<a class="elsevierStyleCrossRef" href="#bib1580"><span class="elsevierStyleSup">117</span></a></p><p id="par0790" class="elsevierStylePara elsevierViewall">Determination of TBS provides information on the changes which treatment may produce on bone microarchitecture&#44;<a class="elsevierStyleCrossRef" href="#bib1720"><span class="elsevierStyleSup">145</span></a> but insufficient data is available to recommend its use in clinical follow-up&#46;</p></span><span id="sec0140" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0200">Therapy failure</span><p id="par0795" class="elsevierStylePara elsevierViewall">The definition of therapeutic failure in the treatment of OP is complex and there are no established criteria&#46; Experts agree that it is advisable to ensure that treatment adherence is correct&#44; confirm an adequate supply of calcium and vitamin D and rule out secondary OP causes&#46; With regard to treatment failure&#44; after one year of treatment with any antiosteoporotic drug&#44; a group of international experts suggest the following criteria of assessment for treatment changes<a class="elsevierStyleCrossRef" href="#bib1715"><span class="elsevierStyleSup">144</span></a>&#58;<ul class="elsevierStyleList" id="lis0045"><li class="elsevierStyleListItem" id="lsti0220"><span class="elsevierStyleLabel">1&#46;</span><p id="par0800" class="elsevierStylePara elsevierViewall">Two or more fragility fractures during treatment&#46;</p></li><li class="elsevierStyleListItem" id="lsti0225"><span class="elsevierStyleLabel">2&#46;</span><p id="par0805" class="elsevierStylePara elsevierViewall">One fragility fracture together with one of the following factors&#58;<ul class="elsevierStyleList" id="lis0050"><li class="elsevierStyleListItem" id="lsti0230"><span class="elsevierStyleLabel">-</span><p id="par0810" class="elsevierStylePara elsevierViewall">Significant loss of BMD &#40;&#62;5&#37; in lumbar spine or &#62;4&#37; in proximal femur&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0235"><span class="elsevierStyleLabel">-</span><p id="par0815" class="elsevierStylePara elsevierViewall">Absence of significant changes in the MBT &#40;reduction of PINP or CTX &#62;25&#37; with antiresorptive treatment&#44; or increase &#62;25&#37; with bone turnover treatment after 6 months&#41;&#46;</p></li></ul></p></li><li class="elsevierStyleListItem" id="lsti0240"><span class="elsevierStyleLabel">3&#46;</span><p id="par0820" class="elsevierStylePara elsevierViewall">Absence of significant changes in the MBT together with a significant loss of BMD&#46;</p></li></ul></p></span><span id="sec0145" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0205">Treatment safety</span><p id="par0825" class="elsevierStylePara elsevierViewall">In general the drugs approved for OP treatment are safe and present with good tolerability&#46;<a class="elsevierStyleCrossRef" href="#bib1725"><span class="elsevierStyleSup">146</span></a> Oral BP may lead to a series of adverse digestive effects &#40;pyrosis&#44; dyspepsia&#44; esophagitis&#44; dysphagia or abdominal pain&#41; and oral effects &#40;conjuntivitis&#44; anterior uveitis&#41;&#44; of minor intensity in most cases&#44; which disappear when the drug is withdrawn&#46; After the first infusion of zoledronic acids symptoms of unclarified origin have been described characterised by fever&#44; myalgias and bone pains and this occurs in between 20&#37; and 30&#37; of patients&#46; In subsequent infusions the symptoms tend to disappear&#46; This effect may occur rarely with oral BP&#46;</p><p id="par0830" class="elsevierStylePara elsevierViewall">Treatment with BP does not increase cardiovascular risk&#46; No association has been demonstrated between the development of auricular fibrillation and treatment with oral BP&#46; In one study an increased risk of auricular fibrillation was observed with the use of intravenous zoledronic acid&#46;<a class="elsevierStyleCrossRef" href="#bib1730"><span class="elsevierStyleSup">147</span></a> Isolated cases of cancer of the oesophagus have been published in patients on oral BP&#44; but the most recent studies have not confirmed this relationship&#46;<a class="elsevierStyleCrossRef" href="#bib1735"><span class="elsevierStyleSup">148</span></a> Osteomuscular pain&#44; kidney damage and hepatotoxicity from BP are exceptional and will rarely lead to withdrawal of the drug&#46;<a class="elsevierStyleCrossRef" href="#bib1740"><span class="elsevierStyleSup">149</span></a> Use of BP is not advised in patients with glomerular filtration rate &#60;30<span class="elsevierStyleHsp" style=""></span>ml&#47;min&#44; since there are no available studies that have demonstrated a reduction in fractures in these patients and on the contrary&#44; they increase the risk of impairment of a reduced remodelling osteodystrophy&#46;</p><p id="par0835" class="elsevierStylePara elsevierViewall">Denosumab&#44; in the guideline approved for the treatment of OP&#44; is a drug which is generally well tolerated&#46; A higher rate of infections has been observed&#44; and in particular cutaneous<a class="elsevierStyleCrossRef" href="#bib1435"><span class="elsevierStyleSup">88</span></a> and urinary&#44;<a class="elsevierStyleCrossRef" href="#bib1745"><span class="elsevierStyleSup">150</span></a> but their overall rate is very low&#46;<a class="elsevierStyleCrossRef" href="#bib1750"><span class="elsevierStyleSup">151</span></a> However&#44; due to their structure&#44; they are not eliminated by the kidney&#44; which is an advantage for patients with kidney diseases where a higher risk of hypocalcaemia must be monitored&#46; As with BP&#44; denosumab should not be used when there is clinical suspicion or histomorphometric evidence of reduced remodelling osteodystrophy&#46;</p><p id="par0840" class="elsevierStylePara elsevierViewall">Adverse reactions to teriparatide are generally not serious&#46; Muscle pain&#44; cramps and dizziness are frequent&#46; Treatment with teriparatide may raise calcaemia and calciuria&#44; and it is therefore advisable to determine the levels of calcium in the blood and urine prior to initiating treatment&#46;</p><p id="par0845" class="elsevierStylePara elsevierViewall">In recent years complications have appeared which are associated with prolonged treatment with antiresorptives &#40;BP and denosumab&#41; and which have generated uncertainty about safety&#46; The relative importance of these rare adverse effects &#40;osteonecrosis of the jawbones and atypical femur fracture&#41; in the treatment of OP is a highly controversial issue&#46;</p><p id="par0850" class="elsevierStylePara elsevierViewall">The fear of patients in suffering these complications may be an impediment for adherence and therapeutic compliance&#44; although the benefit&#8211;risk balance of maintaining treatment is highly favourable for high fracture risk patients&#46; A brief analysis will now be made of both complications&#44; based on the systematic reviews carried out to complete this document&#46;</p></span><span id="sec0150" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0210">Osteonecrosis of the jawbones</span><p id="par0855" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">Recommendation&#58;</span><span class="elsevierStyleItalic">If any invasive dental procedures has been indicated to the OP patient &#40;dental extraction or implant&#41; it is recommended that antiresorptive treatment initiation be postponed until the surgical wound has completely healed</span> &#40;RR&#58; D&#59; AL&#58; 100&#37;&#41;&#46;</p><p id="par0860" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">Recommendation&#58;</span><span class="elsevierStyleItalic">In patients treated with antiresorptives who are going to carry out a dental procedure it is not recommended that they discontinue treatment with BP or denosumab&#46; If other additional osteonecrosis of the jawbone risks prevail or the surgical procedure is to be extensive&#44; temporary suspension of the treatment with BP may be considered</span> &#40;RR&#58; D&#59; AL&#58; 78&#37;&#41;&#46;</p><p id="par0865" class="elsevierStylePara elsevierViewall">Osteonecrosis of the jawbones has been associated with the prolonged use of BP or denosumab&#44; although its rate in patients with OP is very low &#40;between 1&#47;10&#44;000 and 1&#47;100&#44;000&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib1755"><span class="elsevierStyleSup">152&#8211;154</span></a></p><p id="par0870" class="elsevierStylePara elsevierViewall">According to the outcomes of a previous review&#44; published in 2013&#44; available evidence on BP is scarce and of low quality&#46;<a class="elsevierStyleCrossRef" href="#bib1765"><span class="elsevierStyleSup">154</span></a> There is insufficient data to confirm that oral BP or intravenous BP used for OP treatment confers any significant risk of osteonecrosis of the jawbones&#46; There have not been enough studies to assess the role of denosumab in the development of osteonecrosis of the jawbones &#40;level of evidence 3&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib1755"><span class="elsevierStyleSup">152&#44;153</span></a> Several systemic factors such as previous treatment with BP or dental extractions are associated with the development of osteonecrosis of the jawbones in patients treated with denosumab &#40;level of evidence 3&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib1760"><span class="elsevierStyleSup">153</span></a></p><p id="par0875" class="elsevierStylePara elsevierViewall">Several medical associations have published recommendations to reduce the risk of this complication&#46; In general&#44; guidelines include correct dental hygiene in their proposals and dental check-up if poor dental health is observed&#46; If any invasive dental procedures has been indicated &#40;dental extraction or implant&#41; it is recommended that treatment initiation be postponed until the surgical wound has completely healed&#46;<a class="elsevierStyleCrossRef" href="#bib1770"><span class="elsevierStyleSup">155</span></a> The use of CTX marker thresholds have been suggested to assess the baseline risk of osteonecrosis of the jawbones&#46; However&#44; available evidence does not endorse its use&#46;<a class="elsevierStyleCrossRef" href="#bib1775"><span class="elsevierStyleSup">156</span></a></p><p id="par0880" class="elsevierStylePara elsevierViewall">There is some controversy regarding the which approach to take in patients who are already taking BP or denosumab&#46; The majority of guidelines advise not to suspend antiresorptive treatment in non oncological patients&#46; In 2011&#44; the <span class="elsevierStyleItalic">American Dental Association</span> guide recognised that the risk of osteonecrosis of the jawbones was very low in patients with OP&#44; and it was therefore not necessary to suspend an oral BP prior to a dental procedure&#46;<a class="elsevierStyleCrossRef" href="#bib1780"><span class="elsevierStyleSup">157</span></a> However&#44; and according to the recommendations made by the international panel of experts&#44; in patients who have undergone extensive oral surgery and with associated risk factors &#40;diabetes&#44; periodontal disease&#44; immunodeficiency&#44; tobacco habit&#41;&#44; clinical judgement may suggest temporal suspension of treatment&#46;<a class="elsevierStyleCrossRef" href="#bib1770"><span class="elsevierStyleSup">155</span></a> In this situation&#44; and given that withdrawal of denosumab leads to a bone remodelling and the risk of appearance of multiple vertebral fractures&#44; the panel considers that treatment with denosumab should not be interrupted&#46;</p><p id="par0885" class="elsevierStylePara elsevierViewall">During OP treatment&#44; invasive dental procedures may be made only after careful consideration of their necessity&#46; In the case of denosumab&#44; and whenever possible&#44; surgery must be avoided in periods close to drug administation&#46;<a class="elsevierStyleCrossRef" href="#bib1785"><span class="elsevierStyleSup">158</span></a> In this situation a prolonged unnecessary suspension should be avoided&#44; especially in patients treated with denosumab&#46; Should a relevant adverse event occur such as osteonecrosis of the jawbones&#44; and although no scientific evidence demonstrates withdrawal of the drug will help the process evolve&#44; the same document considers it prudent to suspend treatment and assess drug indication with a different mechanism of action&#46;<a class="elsevierStyleCrossRef" href="#bib1770"><span class="elsevierStyleSup">155</span></a></p></span><span id="sec0155" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0215">Atypical femur fracture</span><p id="par0890" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">Recommendation&#58;</span><span class="elsevierStyleItalic">In patients with high fracture risk and prolonged treatment with bisphosphonates &#40;&#62;5 years for orals or &#62;3 years for intravenous&#41; it is recommended not to suspend treatment&#44; since the risk of atypical femur fracture is very low and the benefits of fracture reduction greatly outweigh the risk of atypical fracture</span> &#40;RR&#58; D&#59; AL&#58; 100&#37;&#41;&#46;</p><p id="par0895" class="elsevierStylePara elsevierViewall">Atypical fracture of the femur is a potential complication from prolonged treatment with BP or denosumab&#44; although real incidence is very low&#46;</p><p id="par0900" class="elsevierStylePara elsevierViewall">According to the definition proposed by the <span class="elsevierStyleItalic">American Society for Bone and Mineral Research</span> &#40;ASBMR&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib1790"><span class="elsevierStyleSup">159</span></a> the atypical fracture of the femur is located between the lesser trochanter and the suprachondylar crest and should present with a minimum of 4 out of the following 5 criteria&#58; &#40;1&#41; minimum or absent trauma&#59; &#40;2&#41; origin of the fracture in the external cortical and directed cross-sectionally or obliquely&#59; &#40;3&#41; without comminution or&#44; if this exists&#44; it must be minimal&#59; &#40;4&#41; periostic or endostic thickening of the external&#44; localised cortical&#44; and &#40;5&#41; involvement of the external side cortical &#40;incomplete fracture&#41; or both corticals &#40;complete fracture&#41;&#46; Minor criteria are not essential for diagnosis&#44; but they increase it&#58; &#40;a&#41; cortical thickness increased diffusely in femoral diaphysis&#59; &#40;b&#41; pain in thighs or groin area&#44; prior to fracture&#59; &#40;c&#41; bilateral fracture of similar characteristics&#44; and &#40;d&#41; delay in consolidation&#46;</p><p id="par0905" class="elsevierStylePara elsevierViewall">Apart from prolonged treatment with antiresorptives&#44; the atypical fracture of the femur has also been associated with several comorbidities or with taking medication such as proton pump inhibitors or glucocorticoids&#46;</p><p id="par0910" class="elsevierStylePara elsevierViewall">According to the results of a previous 2011 review&#44; the rate of atypical fracture of the femur was very low and it could not be confirmed that there was a significant increase in the risk of atypical fracture of the femur in patients with Op treated with BP&#46; Since then several poor quality studies have been published which show that the rate of atypical fracture of the femur as very low&#46; Two of the 3 published meta-analyses&#44;<a class="elsevierStyleCrossRefs" href="#bib1795"><span class="elsevierStyleSup">160&#44;161</span></a> based on randomised clinical trials &#40;RCT&#41;&#44; cohort&#44; case and control studies&#44; with a high degree of overlapping&#44; demonstrated a significant increase in the risk of subtrochanteric or diaphysary fracture with the use of BP ranged between 1&#46;70 and 1&#46;99&#44; although with a high level of heterogeneity&#46; In a third meta-analysis which only explored alendronic acid&#44;<a class="elsevierStyleCrossRef" href="#bib1805"><span class="elsevierStyleSup">162</span></a> the relative risk of atypical fracture of the femur with this drug was 3&#46;23 &#40;95&#37; CI&#58; &#46;88&#8211;11&#46;84&#41;&#44; but the differences were not significant&#46; When a stratified analysis was made with the studies to assess the effect of alendronic acid over 5 years&#44; heterogeneity was insignificant&#46; Using a model of fixed effects&#44; the relative risk was 2&#46;55 &#40;95&#37; CI&#58; 2&#46;26&#8211;2&#46;88&#41;&#44; concluding that the alendronic acid did not increase the risk of atypical fracture of the femur short-term&#44; but it did in the long term &#40;&#62;5 years&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib1805"><span class="elsevierStyleSup">162</span></a></p><p id="par0915" class="elsevierStylePara elsevierViewall">A recent systematic review<a class="elsevierStyleCrossRef" href="#bib1805"><span class="elsevierStyleSup">162</span></a> concluded that the rate of atypical fracture of the femur associated with BP was very low&#44; but that the relative risk &#40;RR&#41; increased with prolonged use &#40;especially if it was over 3 years&#41;&#46; According to the authors&#44; the benefits of BP in reduction of OP fractures greatly outweigh the risk of atypical femur fracture&#46; A limiting feature highlighted was that almost all studies were retrospective and of variable duration &#40;4&#8211;9 years&#41;&#44; limiting the interpretation of long term exposure&#46;</p><p id="par0920" class="elsevierStylePara elsevierViewall">Regarding the RCT&#44;<a class="elsevierStyleCrossRefs" href="#bib1810"><span class="elsevierStyleSup">163&#44;164</span></a> isolated cases have been reported on atypical femur fractures&#44; but these studies present with relevant limitations&#44; such as the short duration of the same&#44; the non-inclusion of this outcome as a main variable or the losses in follow-up&#44; which impede the obtainment of reliable outcomes&#46; If we analyse observational studies&#44;<a class="elsevierStyleCrossRefs" href="#bib1820"><span class="elsevierStyleSup">165&#44;166</span></a> the incidence and absolute risk of atypical fracture of the femur in patients treated with BP have very low rates &#40;between 10&#46;8 and 19&#46;1 per 100&#44;000 patients per year&#41;&#46;</p><p id="par0925" class="elsevierStylePara elsevierViewall">The rate of atypical femur fracture represents 0&#46;3&#37; of the total of femur fractures or 5&#37; of the total of subtrochanteric&#47;diaphyseal fractures&#46; Women represent 80&#37; of all diaphyseal fractures and 95&#37; of the atypical fractures of the femur&#44; with a relative risk which is higher in men&#46; The outcome of recent review studies and meta-analyses suggest a favourable benefit&#47;risk ratio to maintain treatment up until 10 years with antiresorptives&#46;</p><p id="par0930" class="elsevierStylePara elsevierViewall">Regarding denosumab&#44; the systematic review results on the risk of atypical femur fracture are very limited due to the scarcity of high quality studies&#46; The studies included were one RCT&#44;<a class="elsevierStyleCrossRef" href="#bib1730"><span class="elsevierStyleSup">147</span></a> two follow-up studies<a class="elsevierStyleCrossRefs" href="#bib1830"><span class="elsevierStyleSup">167&#44;168</span></a> and one cohort study&#46;<a class="elsevierStyleCrossRef" href="#bib1840"><span class="elsevierStyleSup">169</span></a></p><p id="par0935" class="elsevierStylePara elsevierViewall">According to observational studies&#44; long-term treatment with denosumab &#40;between 7 and 10 years&#41; is associated with a nil<a class="elsevierStyleCrossRef" href="#bib1835"><span class="elsevierStyleSup">168</span></a> or very low rate of atypical fracture of the femur &#40;&#46;8 per 10&#44;000 patients per year&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib1830"><span class="elsevierStyleSup">167</span></a> A clinical trial of postmenopausal women with OP who had switched from BP to denosumab was unable to demonstrate that the rare cases of atypical fracture of the femur which appeared early on could be attributable to the use of denosumab&#44; in contrast they appeared to be derived from prior use of BP&#46;<a class="elsevierStyleCrossRef" href="#bib1795"><span class="elsevierStyleSup">160</span></a></p><p id="par0940" class="elsevierStylePara elsevierViewall">Although cases of atypical femur fracture have been described in patients treated with denosumab&#44; the panel of experts decided not to make a specific recommendation on the risk of atypical femur fracture with denosumab due to low evidence and the need for further studies with a higher number of cases and longer time period&#46;</p><p id="par0945" class="elsevierStylePara elsevierViewall">To reduce the clinical impact of atypical femur fracture&#44; in patients under prolonged treatment with BP or denosumab attention must be paid to the presence of pain in the thighs&#46; In these cases it is recommended that X-rays be performed to detect stress fractures or cortical thickening and for early determination of atypical femur fracture&#46; It may also be useful to use magnetic resonance or a bone scan to confirm diagnosis&#46;</p><p id="par0950" class="elsevierStylePara elsevierViewall">Treatment of an atypical femur fracture is surgical&#46; When this complication arises&#44; studies conclude that antiresorptive treatment should be withdrawn&#44; the pain treated&#44; an adequate provision of calcium and vitamin D ensured and a drug with a different mechanism of action be indicated&#46;<a class="elsevierStyleCrossRef" href="#bib1845"><span class="elsevierStyleSup">170</span></a> No control studies exist On the efficacy of teriparatide in patients who have suffered an atypical femur fracture&#46; In a short series of cases&#44; treatment with teriparatide increased the bone mass and the bone remodelling markers&#44; but with no consistent effect on fracture consolidation&#46;<a class="elsevierStyleCrossRef" href="#bib1845"><span class="elsevierStyleSup">170</span></a></p></span></span><span id="sec0160" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0220">Special situations</span><span id="sec0165" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0225">Fragility fracture</span><p id="par0955" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">Recommendation&#58;</span><span class="elsevierStyleItalic">It is recommended that all patients&#8217; &#8805;50 years of age with a recent fragility fracture be assessed systematically to prevent further fractures</span> &#40;RR&#58; D&#59; AL&#58; 100&#37;&#41;&#46;</p><p id="par0960" class="elsevierStylePara elsevierViewall">Patients with fragility fracture have a significant increase in the risk of further fractures&#46; However&#44; it is normal that fewer than 25&#37; of them start treatment for OP after a fracture&#46;<a class="elsevierStyleCrossRef" href="#bib1015"><span class="elsevierStyleSup">4</span></a> The term &#8220;imminent fracture risk&#8221; has recently been introduced to refer to patients with recent fractures&#44; fragile elderly people with frequent falls and fracture patients who have started treatment with high doses of glucocorticoids&#46;<a class="elsevierStyleCrossRef" href="#bib1055"><span class="elsevierStyleSup">12</span></a></p><p id="par0965" class="elsevierStylePara elsevierViewall">In keeping with the EULAR<a class="elsevierStyleCrossRef" href="#bib1850"><span class="elsevierStyleSup">171</span></a> recommendations the panel of experts suggested that all patients with recent osteoporotic fracture aged &#8805;50 years of age should be systematically assessed to prevent new fractures&#46;</p><p id="par0970" class="elsevierStylePara elsevierViewall">The FLS model&#44; or Fracture Unit appears to be the most effective<a class="elsevierStyleCrossRef" href="#bib1855"><span class="elsevierStyleSup">172</span></a> in terms of evaluation and treatment initiation&#46; It is also cost-effective<a class="elsevierStyleCrossRef" href="#bib1860"><span class="elsevierStyleSup">173</span></a> and positive experiences have been had with it in Spain&#46;<a class="elsevierStyleCrossRef" href="#bib1675"><span class="elsevierStyleSup">136</span></a> The central element of a Fracture Unit is the coordinator &#40;in Spain this is usually a medical bone metabolism expert&#41;&#44; who works in close collaboration with a specialised nurse&#46; The keys to success in the Fracture Unit are&#58; &#40;a&#41; identification of all cases&#44; usually from a list of emergencies and of hospitalised patients&#59; &#40;b&#41; study of the patients&#44; including determination of risk factors&#44; DXA and analysis&#59; &#40;c&#41; the advice of the nurse on non pharmacological measures and adherence to medication&#59; &#40;d&#41; early initiation of antifracture treatment and &#40;e&#41; the drawing up of a report with precise indications for the primary care physician&#46;</p><p id="par0975" class="elsevierStylePara elsevierViewall">In patients with fragility fracture the panel of experts concludes that it would be useful to assess fracture risk factors and falls and identify secondary OP&#46; They advise the carrying out of DXA and assessment of the presence of vertebral fractures&#46;</p></span><span id="sec0170" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0230">Vertebral fracture</span><p id="par0980" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">Recommendation&#58;</span><span class="elsevierStyleItalic">The treatment of choice for an acute vertebral fracture is rest&#44; rapidly scaled analgesics to control pain&#44; and if necessary the use of a brace</span> &#40;RR&#58; &#8730;&#59; AL&#58; 100&#37;&#41;&#46;</p><p id="par0985" class="elsevierStylePara elsevierViewall">Acute vertebral fracture may lead to serious pain and disability&#44; lasting for several months&#46;<a class="elsevierStyleCrossRef" href="#bib1865"><span class="elsevierStyleSup">174</span></a> General measures that have been shown to be useful and shorten the recovery period are bedrest &#40;for 4 days or less&#41; and rapidly scaled analgesics &#40;including the use of powerful opiates when necessary&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib1870"><span class="elsevierStyleSup">175</span></a></p><p id="par0990" class="elsevierStylePara elsevierViewall">Ortheses &#40;rigid or semi-rigid brace&#41; are useful for acute episode in combination with analgesic treatment&#44; as they help to immobilise the fracture&#44; reduce load and improve spinal alignment in patients who can tolerate them&#46; The type of orthesis will depend on fracture location&#46; Prolonged use is not advisable&#46; It has not been demonstrated that the rate of new fractures will decrease&#46;<a class="elsevierStyleCrossRef" href="#bib1875"><span class="elsevierStyleSup">176</span></a></p><p id="par0995" class="elsevierStylePara elsevierViewall">In patients with persistent and highly intense pain &#40;visual analogue scale &#91;VAS&#93; &#8805;7&#41;&#44; after 4&#8211;6 weeks of treatment as described above&#44; some studies concluded that facet infiltrations could be considered or radiofrequency ablation of the lumbar medial branch&#44;<a class="elsevierStyleCrossRef" href="#bib1880"><span class="elsevierStyleSup">177</span></a> before prescribing a vertebroplasty or kyphoplasty&#46; According to other studies&#44; in the sub-acute and chronic phase it would be beneficial to have physical therapy using heat applied techniques&#44; ultrasound or hydrotherapy and a progressive initiation of an exercise programme to strengthen the paravertebral and thoracoabdominal muscles&#46;<a class="elsevierStyleCrossRef" href="#bib1885"><span class="elsevierStyleSup">178</span></a> Weight-bearing exercises and balance training prevent falls and fractures and improve the patient&#39;s quality of life&#46;<a class="elsevierStyleCrossRefs" href="#bib1290"><span class="elsevierStyleSup">59&#44;176</span></a></p><span id="sec0175" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0235">Vertebroplasty and kyphoplasty</span><p id="par1000" class="elsevierStylePara elsevierViewall">In which cases would vertebroplasty and kyphoplasty be indicated&#63;</p><p id="par1005" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">Recommendation&#58;</span><span class="elsevierStyleItalic">Vertebroplasty and kyphoplasty are recommended for the treatment of vertebral fracture only in cases of serious refractory pain on a WHO analgesic scale&#44; including opiates</span> &#40;RR&#58; D&#59; AL&#58; 100&#37;&#41;&#46;</p><p id="par1010" class="elsevierStylePara elsevierViewall">Systematic reviews of the clinical efficacy of vertebroplasty in patients with fractures due to OP&#44; with pain which is refractory to analgesic treatment&#44; conclude that in open trials vertebroplasty has better results than an optimum analgesic treatment in improving quality of life and reducing pain and disability&#46;<a class="elsevierStyleCrossRefs" href="#bib1890"><span class="elsevierStyleSup">179&#44;180</span></a> However&#44; in double blind trials there is no evidence that vertebroplasty is superior to placebo with local anaesthesia&#46; Also&#44; after a month&#44; the average pain&#44; according to the VAS&#44; was 5 points in the placebo group and 4&#46;3 points in the vertebroplasty group&#44; with an absolute reduction in pain of 7&#37; and a relative reduction of 10&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib1890"><span class="elsevierStyleSup">179</span></a> Evidence of its clinical efficacy is not consistent&#46; The complications associated with the procedure are rare&#44; but may be serious&#46; Notwithstanding&#44; it cannot be determined with certainty whether vertebroplasty leads to an increased risk of new fractures in adjacent vertebra&#46;<a class="elsevierStyleCrossRefs" href="#bib1890"><span class="elsevierStyleSup">179&#44;180</span></a></p><p id="par1015" class="elsevierStylePara elsevierViewall">Systematic reviews of the clinical efficacy of kyphoplasty conclude that in open studies it has better outcomes than conservative treatment in improving quality of life and reducing pain and disability&#44; but the evidence of its clinical efficacy is not consistent as there are no available double blind studies to compare with placebo&#46;<a class="elsevierStyleCrossRefs" href="#bib1890"><span class="elsevierStyleSup">179&#44;181</span></a></p><p id="par1020" class="elsevierStylePara elsevierViewall">Reduction in pain associated with kyphoplasty analysed through VAS&#44; compared with conservative treatment&#44; was &#8722;1&#46;82 after 30 days&#44; &#8722;1&#46;45 after 3 months and &#8722;1&#46;48 after 6 months&#44; but &#8722;&#46;84 and &#8722;&#46;69 after 12 and 24 months&#44; respectively&#46;<a class="elsevierStyleCrossRef" href="#bib1900"><span class="elsevierStyleSup">181</span></a> The authors conclude that vertebroplasty and kyphoplasty could improve quality of life and reduce pain in vertebral fractures refractory to analgesic treatment&#44; with a doubtful increase in the rate of new fractures in the adjacent vertebra&#46; There is therefore not sufficient evidence for their recommendation in standard clinical practice&#46;</p></span></span><span id="sec0180" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0240">Osteoporosis from glucocorticoids</span><p id="par1025" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">Recommendation&#58;</span><span class="elsevierStyleItalic">In patients who receive or who are going to receive treatment with glucocorticoids fracture risk must be assessed and the initiation of treatment for osteoporosis as soon as possible</span> &#40;RR&#58; D&#59; AL&#58; 100&#37;&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par1030" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">Recommendation&#58;</span><span class="elsevierStyleItalic">It is recommended that pharmacological treatment be initiated to prevent OP in patients who are going to receive glucocorticoids for over 3 months in the following cases</span> &#40;RR&#58; D&#41;&#58;<ul class="elsevierStyleList" id="lis0055"><li class="elsevierStyleListItem" id="lsti0245"><span class="elsevierStyleLabel">1&#46;</span><p id="par1035" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Patients with an initial dose &#8805;30 mg&#47;day of prednisone&#46; In these cases it is recommended that treatment be imitated for the OP immediately &#40;AL&#58; 100&#37;&#41;</span>&#46;</p></li><li class="elsevierStyleListItem" id="lsti0250"><span class="elsevierStyleLabel">2&#46;</span><p id="par1040" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Postmenopausal women and men &#62;50 years of age with doses of prednisone &#8805;5</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">mg&#47;day who also present with some of the following conditions&#58;</span><ul class="elsevierStyleList" id="lis0060"><li class="elsevierStyleListItem" id="lsti0255"><span class="elsevierStyleLabel">a&#41;</span><p id="par1045" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Previous fragility fracture &#40;AL&#58; 100&#37;&#41;</span>&#46;</p></li><li class="elsevierStyleListItem" id="lsti0260"><span class="elsevierStyleLabel">b&#41;</span><p id="par1050" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Low BMD &#40;T-score &#8804;&#8722;1&#46;5 SD in spine or hip&#41; &#40;AL&#58; 89&#37;&#41;</span>&#46;</p></li><li class="elsevierStyleListItem" id="lsti0265"><span class="elsevierStyleLabel">c&#41;</span><p id="par1055" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">High fracture risk&#58; FRAX</span><span class="elsevierStyleSup"><span class="elsevierStyleItalic">&#174;</span></span><span class="elsevierStyleItalic">for hip &#8805;3&#37; or for primary fracture &#8805;10&#37; without BMD or &#8805;7&#46;5&#37; with BMD &#40;AL&#58; 78&#37;&#41;</span>&#46;</p></li></ul></p></li><li class="elsevierStyleListItem" id="lsti0270"><span class="elsevierStyleLabel">3&#46;</span><p id="par1060" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Premenopausal women and men &#60;50 years of age and dose &#8805;7&#46;5<span class="elsevierStyleHsp" style=""></span>mg&#47;day of prednisone who also present with some of the following conditions&#58;</span><ul class="elsevierStyleList" id="lis0065"><li class="elsevierStyleListItem" id="lsti0275"><span class="elsevierStyleLabel">a&#41;</span><p id="par1065" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Previous fragility fracture &#40;AL&#58; 100&#37;&#41;</span>&#46;</p></li><li class="elsevierStyleListItem" id="lsti0280"><span class="elsevierStyleLabel">b&#41;</span><p id="par1070" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Low BMD &#40;Z-score &#8804;&#8722;3 SD&#41; &#40;AL&#58; 78&#37;&#41;</span>&#46;</p></li></ul></p></li></ul></p><p id="par1075" class="elsevierStylePara elsevierViewall">OP induced by glucocorticoids is the most frequent cause of secondary OP&#44; and is associated with the presence of fractures in up to 30&#37;&#8211;50&#37; of cases&#46;<a class="elsevierStyleCrossRef" href="#bib1905"><span class="elsevierStyleSup">182</span></a> The risk of fracture depends on factors such as age&#44; prior BMD&#44; daily accumulated dose of glucocorticoids and baseline disease&#46; The loss of BMD is fast&#44; especially in the first 6&#8211;12 months&#44; even with low doses of glucocorticoids&#44; with trabecular bone being the most affected&#46;<a class="elsevierStyleCrossRef" href="#bib1905"><span class="elsevierStyleSup">182</span></a> According to studies&#44; the fractures associated with treatment with glucocorticoids appear with BMD which is not too low&#44; due to the fact that the glucocorticoid mainly affects the whole bone micro architecture&#44; and the TBS and FRAX<span class="elsevierStyleSup">&#174;</span> adjusted with TBS could have a certain additional usefulness in the assessment of the risk of these patients&#46;<a class="elsevierStyleCrossRef" href="#bib1910"><span class="elsevierStyleSup">183</span></a> However&#44; the application of the FRAX<span class="elsevierStyleSup">&#174;</span> in OP through glucocorticoids has certain limitations and underestimates the real risk of fracture&#44; since it does not adjust from accumulated dose from daily dose or treatment duration&#46;</p><p id="par1080" class="elsevierStylePara elsevierViewall">ACR recommendations consider that in patients who receive or are going to receive treatment with glucocorticoids the fracture risk must be assessed &#40;preferably using FRAX<span class="elsevierStyleSup">&#174;</span>&#41; and treatment initiation as soon as possible should be assessed&#46; Furthermore&#44; general preventative OP measures would have to be used in all patients&#44; such as healthy life habits for bones and diet &#40;see section on non pharmacological treatment&#44; calcium and vitamin D&#41;&#46; Furthermore&#44; the lowest possible dose of glucocorticoid should be used and for as short a time as possible&#44; and using immunosuppressants if necessary&#46;<a class="elsevierStyleCrossRef" href="#bib1175"><span class="elsevierStyleSup">36</span></a></p><p id="par1085" class="elsevierStylePara elsevierViewall">In patients with an intermittent corticoid regime and who have an accumulated dose of prednisone &#62;5<span class="elsevierStyleHsp" style=""></span>g&#47;year or those with annual losses of BMD above 10&#37; the panel of experts consider that treatment for OP would also be indicated&#46;</p><p id="par1090" class="elsevierStylePara elsevierViewall">Premenopausal women or men &#60;50 years of age are at a lower fracture risk&#46; There are also fewer data on efficacy and safety or OP treatments for this population group and treatment indications appear to be more restrictive&#46;</p><p id="par1095" class="elsevierStylePara elsevierViewall">The pharmacological treatment of choice is oral BP &#40;risedronic acid and alendronic acid&#41; or intravenous zoledronic acid since they stabilise or increase the BMD and reduce the risk of vertebral fractures in comparison with control groups&#46;<a class="elsevierStyleCrossRef" href="#bib1915"><span class="elsevierStyleSup">184</span></a> According to the technical specifications&#44; the drugs which currently have an glucocorticoid OP indication in Spain are teriparatide&#44; risedronic acid and zoledronic acid&#46;</p><p id="par1100" class="elsevierStylePara elsevierViewall">In women with established OP&#44; teriparatide has been demonstrated to be more effective than risedronic acid in reducing vertebral fractures and clinical fractures&#44; regardless of having received previous treatment with BP&#46;<a class="elsevierStyleCrossRef" href="#bib1920"><span class="elsevierStyleSup">185</span></a> In fact&#44; teriparatide has demonstrated superiority against alendronic acid in both gain in BMD and reduction in morphometric vertebral fractures&#44; in premenopausal&#44; postmenopausal women and men treated with glucocorticoids after 18 months of follow-up&#46;<a class="elsevierStyleCrossRef" href="#bib1925"><span class="elsevierStyleSup">186</span></a> As a result&#44; the panel of experts consider that high risk patients or those refractory or who have contraindications to antiresorptive treatment could evaluate the treatment with teriparatide&#46;<a class="elsevierStyleCrossRef" href="#bib1230"><span class="elsevierStyleSup">47</span></a></p><p id="par1105" class="elsevierStylePara elsevierViewall">In patients who start or have already received glucocorticoids&#44; the administration of denosumab for 12 months has shown an increase in BMD which is significantly higher than with risedronic acid&#44;<a class="elsevierStyleCrossRef" href="#bib1930"><span class="elsevierStyleSup">187</span></a> and the <span class="elsevierStyleItalic">European Medicines Agency</span> &#40;EMA&#41; has recommended that denosumab be added into the technical specification as a new indication&#58; for treatment of the loss of BMD associated with the prolonged use of glucocorticoids in adult patients at high risk of fracture&#46;</p><p id="par1110" class="elsevierStylePara elsevierViewall">According to the recommendations of the International Groups&#44; the treatment of choice should be maintained for as long as treatment with glucocorticoids lasts and for at least 6 months after suspending the glucocorticoid&#44; unless fractures exist&#44; in which case it would be continued&#46;<a class="elsevierStyleCrossRef" href="#bib1175"><span class="elsevierStyleSup">36</span></a></p></span><span id="sec0185" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0245">Rheumatic&#44; inflammatory and systemic diseases</span><p id="par1115" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">Recommendation&#58;</span><span class="elsevierStyleItalic">It is advisable to assess the risk of fracture and consider performing DXA in patients with rheumatoid arthritis&#44; systemic lupus erythematosus and ankylosing spondylitis especially those over 50 years of age and who are being treated with glucocorticoids or with a severe or evolved disease</span> &#40;RR&#58; &#8730;&#59; AL&#58; 100&#37;&#41;&#46;</p><p id="par1120" class="elsevierStylePara elsevierViewall">Patients with rheumatoid arthritis&#44; systemic lupus erythematosus and ankylosing spondylitis are at greater risk of <span class="elsevierStyleItalic">OP</span> and&#47;or fractures&#46;<a class="elsevierStyleCrossRefs" href="#bib1935"><span class="elsevierStyleSup">188&#8211;194</span></a> One study reported an increased fracture risk in psoriasis arthritis and in severe psoriasis&#46;<a class="elsevierStyleCrossRef" href="#bib1970"><span class="elsevierStyleSup">195</span></a> The conclusions of some studies in patients with rheumatoid arthritis advise screening for fragility fracture and performing rheumatoid DXA&#44; especially in patients &#62;50 years of age in those with severe disease or evolved disease or those treated with glucocorticoids&#46;<a class="elsevierStyleCrossRefs" href="#bib1935"><span class="elsevierStyleSup">188&#44;189</span></a> Moreover&#44; several documents of consensus on the management of comorbidities in rheumatoid arthritis&#44; psoriasis arthritis and systemic lupus erythematosus suggested making an accurate prophylaxis of OP&#46;<a class="elsevierStyleCrossRefs" href="#bib1975"><span class="elsevierStyleSup">196&#8211;198</span></a> In relation to antifracture treatments&#44; all the drugs approved for OP were used&#46; In the case of denosumab&#44; safety data was limited in patients treated with biologic agents for their baseline disease&#44; although according to the outcome of some studies there does not appear to be a different safety profile from the postmenopausal OP one&#46;<a class="elsevierStyleCrossRef" href="#bib1990"><span class="elsevierStyleSup">199</span></a></p></span><span id="sec0190" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0250">Osteoporosis in the male</span><p id="par1125" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">Recommendation&#58;</span><span class="elsevierStyleItalic">The study of the causes of secondary osteoporosis in all men with low bone mass or fragility fracture is recommended</span> &#40;RR&#58; D&#59; AL&#58; 100&#37;&#41;&#46;</p><p id="par1130" class="elsevierStylePara elsevierViewall">It has been observed in different studies that OP in the male is underdiagnosed&#46;<a class="elsevierStyleCrossRef" href="#bib1995"><span class="elsevierStyleSup">200</span></a> in fact it has been estimated that a third of hip fractures worldwide occur in males&#44; especially after the age of 70 years&#46; Furthermore&#44; mortality after a hip fracture &#40;over 37&#37; in the first year&#41; is higher than that in women&#46;<a class="elsevierStyleCrossRef" href="#bib2000"><span class="elsevierStyleSup">201</span></a> Also&#44; in the male secondary OP is more frequent and studies therefore conclude that appropriate&#44; accurate clinical assessment is needed for systematic exclusion&#46; The most frequent OP causes and risk factors in the man are hypogonadism&#44; alcohol consumption&#44; tobacco and glucocorticoids&#46; Fracture risk assessment in the male would include clinical risk factors&#44; the existence of previous fractures and the measurement of BMD by DXA &#40;if indicated&#41; to better stratify those patients more susceptible for treatment&#46;<a class="elsevierStyleCrossRef" href="#bib2005"><span class="elsevierStyleSup">202</span></a> With regard to DXA&#44; the same reference values are used in men as in women&#46;<a class="elsevierStyleCrossRef" href="#bib2010"><span class="elsevierStyleSup">203</span></a></p><p id="par1135" class="elsevierStylePara elsevierViewall">With regard to non pharmacological prevention measures&#44; the same may be considered as for OP in women&#46; For hormonal treatment&#44; there are no data on fracture reduction efficacy with testosterone treatment&#44; and the experts therefore only indicate treatment in males with symptomatic hypogonadism and also advising it should be combined with another antiosteoporotic treatment&#46;<a class="elsevierStyleCrossRef" href="#bib2015"><span class="elsevierStyleSup">204</span></a> The drugs which have shown improvement of BMD and reduction of vertebral risk fracture both in eugonadal and hypogonadal males are oral BP &#40;alendronic acid and risedronic acid&#41;&#44;<a class="elsevierStyleCrossRefs" href="#bib2020"><span class="elsevierStyleSup">205&#44;206</span></a> zoledronic acid &#40;the only one which was established as the primary aim&#41;<a class="elsevierStyleCrossRef" href="#bib2030"><span class="elsevierStyleSup">207</span></a> and teriparatide&#46;<a class="elsevierStyleCrossRefs" href="#bib2035"><span class="elsevierStyleSup">208&#44;209</span></a> Denosumab was also approved in males with a high fracture risk and to reduce the loss of BMD in the patient with prostate cancer in androgen deprivation treatment&#46;<a class="elsevierStyleCrossRef" href="#bib2045"><span class="elsevierStyleSup">210</span></a> All these drugs&#44; except the alendronic acid&#44; have an indication in Spain for OP in the male&#46;</p></span><span id="sec0195" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0255">Osteoporosis in premenopausal women</span><p id="par1140" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">Recommendation&#58;</span><span class="elsevierStyleItalic">It is recommended that a study of secondary osteoporosis causes be made in all premenopausal women with a low bone mass measured by DXA or with a fragility fracture</span> &#40;RR&#58; &#8730;&#59; AL&#58; 100&#37;&#41;&#46;</p><p id="par1145" class="elsevierStylePara elsevierViewall">According to the different scientific societies and expert groups&#44; in the premenopausal woman a DXA should be carried out when there are fragility fractures and&#47;or risk factors associated with the loss of bone mass&#46;<a class="elsevierStyleCrossRefs" href="#bib1205"><span class="elsevierStyleSup">42&#44;211</span></a> In this patient group the <span class="elsevierStyleItalic">Z</span>-score would have to be used &#40;which compares with individuals of the same age and sex&#41; instead of the <span class="elsevierStyleItalic">T</span>-score&#46;<a class="elsevierStyleCrossRefs" href="#bib1205"><span class="elsevierStyleSup">42&#44;211&#44;212</span></a> Thus&#44; &#8220;low bone mass&#8221; is considered when the <span class="elsevierStyleItalic">Z</span>-score is lower than &#8722;2 SD&#46;<a class="elsevierStyleCrossRef" href="#bib2050"><span class="elsevierStyleSup">211</span></a> The presence of fragility fractures and particularly when associated with low bone mass&#44; means that OP diagnosis may be established in the premenopausal woman&#46;<a class="elsevierStyleCrossRef" href="#bib2055"><span class="elsevierStyleSup">212</span></a></p><p id="par1150" class="elsevierStylePara elsevierViewall">Considering that over 50&#37; of premenopausal women with OP present with a secondary OP<a class="elsevierStyleCrossRefs" href="#bib2055"><span class="elsevierStyleSup">212&#44;213</span></a> the experts recommend making an exhaustive study to rule out an underlying cause&#44;<a class="elsevierStyleCrossRefs" href="#bib2055"><span class="elsevierStyleSup">212&#44;213</span></a> with the most frequent being the following&#58; treatment with glucocorticoids&#44; oestrogen deficit&#44; malabsorption diseases and OP associated with pregnancy or breast feeding&#46;<a class="elsevierStyleCrossRef" href="#bib2055"><span class="elsevierStyleSup">212</span></a> Idiopathic forms are frequent in premenopausal women and may be associated with hypercalciuria and with a family history of OP&#46;<a class="elsevierStyleCrossRef" href="#bib2060"><span class="elsevierStyleSup">213</span></a></p><p id="par1155" class="elsevierStylePara elsevierViewall">The therapeutic approach in the premenopausal woman includes optimum calcium and vitamin D intake&#44; regular physical exercise&#44; suspending tobacco consumption&#44; limiting alcohol consumption and treating the underlying cause&#46;<a class="elsevierStyleCrossRef" href="#bib2055"><span class="elsevierStyleSup">212</span></a></p><p id="par1160" class="elsevierStylePara elsevierViewall">For premenopausal OP experts&#44; the specific antiosteoporotic drugs &#40;BP&#44; teriparatide&#44; denosumab&#41; will be considered in patients with fragility fracture or for certain secondary causes such as treatment with glucocorticoids&#46;<a class="elsevierStyleCrossRef" href="#bib2060"><span class="elsevierStyleSup">213</span></a> The drugs which they have studied in premenopausal OP are BP &#40;alendronic acid and risedronic acid&#41; and teriparatide&#46;<a class="elsevierStyleCrossRef" href="#bib2055"><span class="elsevierStyleSup">212</span></a> According to experts&#44; in young women certain caution should be used in the administration of BP given its long retention in the bone tissue&#44; particularly in women who wish to get pregnant in the future&#46; They also conclude that none of these drugs should be used in pregnancy &#40;BP and teriparatide are in the C category according to the FDA&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib2065"><span class="elsevierStyleSup">214&#44;215</span></a> With regard to the SERM&#44; it seems reasonable to avoid its use in premenopausal women&#44; whilst with denosumab there is only an indication in postmenopausal OP &#40;according to the FDA&#58; category in pregnancy&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib2055"><span class="elsevierStyleSup">212</span></a></p><p id="par1165" class="elsevierStylePara elsevierViewall">Some experts suggests that in fertile women anti conceptive measures should be prescribed if any antiosteoporotic treatment is initiated&#46;<a class="elsevierStyleCrossRef" href="#bib2060"><span class="elsevierStyleSup">213</span></a></p></span><span id="sec0200" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0260">Other special situations&#58; kidney disease&#44; liver disease and digestive problems</span><span id="sec0205" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0265">Chronic renal disease</span><p id="par1170" class="elsevierStylePara elsevierViewall">In patients with chronic renal disease &#40;CRD&#41; certain differential aspects should be taken into consideration with postmenopausal OP&#58; &#40;1&#41; DXA does not discriminate the type of underlying bone disease and &#40;2&#41; renal osteodystrophy should be excluded&#44; particularly dynamic bone disease &#40;very low osteodystrophy with remodelling&#41; in chronic dialysis patients&#44; since this contraindicates the use of antiresorptives&#46; PTH levels &#60;120<span class="elsevierStyleHsp" style=""></span>pg&#47;ml with low alkaline phosphatase suggest the presence of dynamic bone disease&#46;<a class="elsevierStyleCrossRef" href="#bib2075"><span class="elsevierStyleSup">216</span></a></p><p id="par1175" class="elsevierStylePara elsevierViewall">With regard to a deficiency of vitamin D in the CRD&#44; in states 3&#8211;5D&#44; the experts consider the use of therapeutic strategies similar to those accepted for the general population to be appropriate&#46;</p><p id="par1180" class="elsevierStylePara elsevierViewall">Regarding antifracture treatments for stage 1&#8211;2 patients and filtered &#62;35<span class="elsevierStyleHsp" style=""></span>ml&#47;min&#44; its use is mostly similar to that of patients without CRD&#46;<a class="elsevierStyleCrossRefs" href="#bib2080"><span class="elsevierStyleSup">217&#44;218</span></a></p><p id="par1185" class="elsevierStylePara elsevierViewall">The technical specifications of the drugs indicates that BP&#44; teriparatide and raloxifene are not recommended when filtration is &#60;30<span class="elsevierStyleHsp" style=""></span>ml&#47;min &#40;&#60;35<span class="elsevierStyleHsp" style=""></span>ml&#47;min for alendronic acid and zoledronic acid&#41;&#46; However&#44; some post hoc studies conducted with risedronic acid<a class="elsevierStyleCrossRef" href="#bib2090"><span class="elsevierStyleSup">219</span></a>and raloxifene<a class="elsevierStyleCrossRefs" href="#bib2095"><span class="elsevierStyleSup">220&#44;221</span></a> in patients with glomerular filtration between 15 and 30<span class="elsevierStyleHsp" style=""></span>ml&#47;min &#40;stage 4&#41; have shown these drugs demonstrate most efficacy and safety&#46; Notwithstanding&#44; the limited evidence of this type of post hoc study must be borne in mind&#46; Bazedoxifene has not been sufficiently documented in patients with filtration &#60;30<span class="elsevierStyleHsp" style=""></span>ml&#47;min&#46; Denosumab does not require dose adjustment in kidney failure&#44; but the risk of hypocalcaemia is higher&#44; and it is therefore advised to optimise calcium and vitamin D supplements&#46; Evidence of their safety in patients with stage 4 CRD and in haemodialysis is also limited due to the post hoc studies having a limited number of patients&#46;<a class="elsevierStyleCrossRef" href="#bib2105"><span class="elsevierStyleSup">222</span></a></p></span><span id="sec0210" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0270">Chronic liver disease</span><p id="par1190" class="elsevierStylePara elsevierViewall">According to the experts&#44; patient management with chronic liver disease includes evaluation of factors which lead to bone loss and the increase in fracture risk such as malnutrition&#44; vitamin D deficit&#44; intensity of cholestasis&#44; glucocorticoids and hypogonadism&#46; The pharmacological studies of reduction in patients with liver disease are limited&#44; with no contraindications existing for the use of BP&#44; which increase BMD&#46;<a class="elsevierStyleCrossRef" href="#bib2110"><span class="elsevierStyleSup">223</span></a> There is not enough experience with other treatments&#46;</p></span><span id="sec0215" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0275">Digestive diseases</span><p id="par1195" class="elsevierStylePara elsevierViewall">Studies conclude that management of patients with celiac disease&#44; inflammatory bowel disease&#44; and bariatric surgery should consider malabsorption and malnutrition &#40;evaluate calcium and vitamin D supplements&#41;&#44; as well as the use of glucocorticoids&#46; In inflammatory bowel disease the BP reduce the risk of vertebral fracture&#46;<a class="elsevierStyleCrossRef" href="#bib2115"><span class="elsevierStyleSup">224</span></a></p><p id="par1200" class="elsevierStylePara elsevierViewall">According to the data sheet&#44; oral BP are contraindicated in patients with esophageal anomalies and other factors which may delay emptying&#44; such as stenos is and acalasia&#46; The panel of experts consider that when oral antiresorptive therapy is contraindicated&#44; it is regarded as ineffective due to serious malabsorption is not tolerated&#44; and parenteral route treatment may be considered&#46;<a class="elsevierStyleCrossRef" href="#bib1230"><span class="elsevierStyleSup">47</span></a></p></span></span></span><span id="sec0220" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0280">New treatments</span><p id="par1205" class="elsevierStylePara elsevierViewall">Two new drugs for OP treatment&#58; romosozumab and abaloparatide are currently in an advanced phase of clinical development&#46;</p><p id="par1210" class="elsevierStylePara elsevierViewall">Romosozumab is a humanised IgG2 monoclonal antibody which links and blocks sclerostin&#46; It is administered monthly subcutaneously for a year&#44; followed by denosumab or alendronic acid for a further year and has shown a significant reduction in the incidence of new vertebral and non vertebral fractures&#46;<a class="elsevierStyleCrossRefs" href="#bib2120"><span class="elsevierStyleSup">225&#44;226</span></a> in one of the studies an increase in the rate of serious adverse cardiovascular events was observed compared with alendronic acid&#44;<a class="elsevierStyleCrossRef" href="#bib2125"><span class="elsevierStyleSup">226</span></a> which motivated a requirement by the US Food and Drug Administration &#40;FDA&#41; to provide the results of additional studies&#46;</p><p id="par1215" class="elsevierStylePara elsevierViewall">Abaloparatide is a synthetic peptide which activate the type 1 receptor of the PTH&#44; approved by the FDA in 2017 and rejected by the EMA in 2018&#46; In daily subcutaneous administration it obtained a significant reaction in the rate of vertebral and non vertebral fractures compared with placebo&#44; with no differences to teriparatide&#46;<a class="elsevierStyleCrossRef" href="#bib2130"><span class="elsevierStyleSup">227</span></a> Its safety and tolerability profile was similar to teriparatide&#44; but with a lower rate of hypercalcaemia&#46;</p></span><span id="sec0225" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0285">Conclusion</span><p id="par1220" class="elsevierStylePara elsevierViewall">As mentioned in the introduction&#44; the aim of this document was to provide an update on the new advances in the different aspects of OP relating to clinical practice&#58; diagnosis&#44; evaluation&#44; treatment and follow-up&#46;</p><p id="par1225" class="elsevierStylePara elsevierViewall">The document is based on a critical review of the previous consenus&#44;<a class="elsevierStyleCrossRef" href="#bib1020"><span class="elsevierStyleSup">5</span></a> the best available scientific evidence and expert clinical experience&#46; This was a joint task between panel members and the SER Unit of Research which&#44; together with SER reviewers&#44; carried out an extensive systematic review on the different areas of interest and provided the necessary scientific rigour to produce the recommendations with their level of evidence and also their level of consensus&#44; to provide the reader with the most objective evaluation of these recommendations&#46;</p><p id="par1230" class="elsevierStylePara elsevierViewall">The new definition of OP is incorporated into the diagnostic assessment of this document&#44; and which encompasses patients with fragility fractures and low bone mass&#44; the concept of imminent risk of fracture and the utility of TBS&#46;</p><p id="par1235" class="elsevierStylePara elsevierViewall">With regard to treatment&#44; the effectiveness of each drug for the prevention of fractures together with several selection criteria such as cost-effectiveness&#44; the existence of multiple fractures or the limitations for oral use are presented&#46; The panel members assessed the possibility of including an extensive treatment decision algorithm no agreement was reached on this&#46;</p><p id="par1240" class="elsevierStylePara elsevierViewall">The SER reviewers for their part have updated osteonecrosis of the jawbone and atypical femur fracture guidelines&#46; Special situations were maintained in keeping with the 2011 recommendations&#44; adding OP of inflammatory rheumatisms and a few precautions which should be taken into account in patients with kidney disease and gastrointestinal and hepatic problems&#46; Finally&#44; a section on the new treatments &#40;romosozumab and abaloparatide&#41; was produced&#46;</p><p id="par1245" class="elsevierStylePara elsevierViewall">We would like to highlight from these recommendations that fracture risk and treatment indication were the issues most debated among panel members&#46; The use of the FRAX<span class="elsevierStyleSup">&#174;</span> was unanimously accepted for hip fracture with the threshold of 3&#37; whilst the level of agreement for primary fracture was somewhat lower&#46; In the document the reason why of this discrepancy was exposed&#44; which was basically derived from the absence of sufficient studies on the calibration of the FRAX<span class="elsevierStyleSup">&#174;</span> for the Spanish population&#46;</p><p id="par1250" class="elsevierStylePara elsevierViewall">To conclude&#44; we may say that the recommendations of this document are a draft consultation framework for OP management&#46; They are general regulations which require individualisation in each case and this is the role we must accept as professionals&#46;</p></span><span id="sec0230" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0290">Conflict of interests</span><p id="par1255" class="elsevierStylePara elsevierViewall">Antonio Naranjo Hern&#225;ndez received financing from Amgen&#44; Lilly and FAES for attendance to courses&#47;congresses&#44; fees from Amgen for congress presentations and grants from FHOEMO-Amgen and Lilly to contract staff and provide IT teams to the service&#46;</p><p id="par1260" class="elsevierStylePara elsevierViewall">Mar&#237;a Pilar Aguado Ac&#237;n received financing from Lilly for attendance to congresses&#59; fees from Alexion&#44; Faes&#44; Lilly and de Rubi&#243; for presentations and financing for educational programmes in the Rheumatology Unit&#46;</p><p id="par1265" class="elsevierStylePara elsevierViewall">Luis Arboleya Rodr&#237;guez received financing from Janssen-Cilag&#44; L&#225;cer and Lilly for attendance at congresses and received fees from Pfizer and Lilly for congress presentations&#46;</p><p id="par1270" class="elsevierStylePara elsevierViewall">Enrique Casado Burgos received financing from Amgen&#44; Lilly&#44; FAES&#44; Gebro&#44; ItalDrug and Rubi&#243; for attendance to courses&#47;congresses and fees for presentations&#46;</p><p id="par1275" class="elsevierStylePara elsevierViewall">Santos Casta&#241;eda Sanz received financing from Amgen for attendance to courses&#47;congresses&#59; fees from Lilly for congress presentations&#59; and financial aid from Amgen for consultation for pharmaceutical companies or other technologies and for educational programmes or courses&#46;</p><p id="par1280" class="elsevierStylePara elsevierViewall">Jodi Fitter Arrested received financing from Novartis&#44; Roche&#44; MSD&#44; Amgen&#44; Lilly&#44; Maharani&#44; UCB and Pfizer for attendance to courses&#47;congresses&#59; fees from Amgen-Ferrier&#44; Roche&#44; Maharani and Amgen for congress presentations and received financing from UCB to participate in a research study&#46;</p><p id="par1285" class="elsevierStylePara elsevierViewall">Labia Gofer Sale received financing from Lilly for attendance to congresses&#59; fees from Lilly&#44; Amgen and FAES Farman e for congress presentations&#59; and financing from Alexion for research projects&#46;</p><p id="par1290" class="elsevierStylePara elsevierViewall">Carmen Gomez Vaquero received financing from Abby&#44; Amgen&#44; Bristol&#44; Lilly&#44; Maharani&#44; MSD&#44; Pfizer&#44; Procter Gamble&#44; Roche&#44; Sandoz&#44; Servicer&#44; UCB for attendance to courses&#47;congresses&#59; fees from Abbie&#44; Amgen&#44; Lilly&#44; MSD&#44; Pierre Fabr&#233;&#44; Roche and UCB for congress presentations&#59; financing from Lilly for educational programmes or courses&#59; financing from Novartis&#44; Amgen and Lilly for participating in a research study&#59; financial aid from Nycomed Pharma for consultation for pharmaceutical companies or other technologies&#59; and received financing from Lilly for educational programmes or courses for the unit&#46;</p><p id="par1295" class="elsevierStylePara elsevierViewall">N&#250;ria Gua&#241;abens Gay received financing from Amgen y Lilly for attendance to courses&#47;congresses&#44; for congress presentations and for educational programmes or courses&#59; financing from Amgen to participate in a research study and financial aid from Lilly&#44; Amgen&#44; UCB y Alexion as consultation for pharmaceutical companies&#46;</p></span></span>"
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              "titulo" => "Fracture risk factors"
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              "titulo" => "Evaluation of fracture risk"
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                0 => array:2 [
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                  "titulo" => "Bone densimetry"
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                  "titulo" => "Bone densitometry indications"
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                2 => array:2 [
                  "identificador" => "sec0065"
                  "titulo" => "Trabecular Bone Score"
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              ]
            ]
            3 => array:2 [
              "identificador" => "sec0070"
              "titulo" => "Analysis"
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              "identificador" => "sec0075"
              "titulo" => "Bone turnover markers"
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            5 => array:2 [
              "identificador" => "sec0080"
              "titulo" => "Vertebral fracture screening"
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        ]
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            0 => array:2 [
              "identificador" => "sec0090"
              "titulo" => "Non pharmacological therapies"
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            1 => array:2 [
              "identificador" => "sec0095"
              "titulo" => "Calcium and vitamin D"
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            2 => array:2 [
              "identificador" => "sec0100"
              "titulo" => "Treatment to prevent fractures"
            ]
            3 => array:2 [
              "identificador" => "sec0105"
              "titulo" => "Antifracture treatment choice"
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            4 => array:2 [
              "identificador" => "sec0110"
              "titulo" => "Sequential and combined therapy"
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            5 => array:3 [
              "identificador" => "sec0115"
              "titulo" => "Treatment duration"
              "secciones" => array:2 [
                0 => array:2 [
                  "identificador" => "sec0120"
                  "titulo" => "Treatment suspension or discontinuation"
                ]
                1 => array:3 [
                  "identificador" => "sec0125"
                  "titulo" => "Follow-up&#44; monitorisation and adherence"
                  "secciones" => array:1 [ …1]
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              ]
            ]
            6 => array:2 [
              "identificador" => "sec0135"
              "titulo" => "Monitorisation"
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            7 => array:2 [
              "identificador" => "sec0140"
              "titulo" => "Therapy failure"
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            8 => array:2 [
              "identificador" => "sec0145"
              "titulo" => "Treatment safety"
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            9 => array:2 [
              "identificador" => "sec0150"
              "titulo" => "Osteonecrosis of the jawbones"
            ]
            10 => array:2 [
              "identificador" => "sec0155"
              "titulo" => "Atypical femur fracture"
            ]
          ]
        ]
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          "identificador" => "sec0160"
          "titulo" => "Special situations"
          "secciones" => array:7 [
            0 => array:2 [
              "identificador" => "sec0165"
              "titulo" => "Fragility fracture"
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            1 => array:3 [
              "identificador" => "sec0170"
              "titulo" => "Vertebral fracture"
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                0 => array:2 [
                  "identificador" => "sec0175"
                  "titulo" => "Vertebroplasty and kyphoplasty"
                ]
              ]
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            2 => array:2 [
              "identificador" => "sec0180"
              "titulo" => "Osteoporosis from glucocorticoids"
            ]
            3 => array:2 [
              "identificador" => "sec0185"
              "titulo" => "Rheumatic&#44; inflammatory and systemic diseases"
            ]
            4 => array:2 [
              "identificador" => "sec0190"
              "titulo" => "Osteoporosis in the male"
            ]
            5 => array:2 [
              "identificador" => "sec0195"
              "titulo" => "Osteoporosis in premenopausal women"
            ]
            6 => array:3 [
              "identificador" => "sec0200"
              "titulo" => "Other special situations&#58; kidney disease&#44; liver disease and digestive problems"
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                0 => array:2 [
                  "identificador" => "sec0205"
                  "titulo" => "Chronic renal disease"
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                1 => array:2 [
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                  "titulo" => "Chronic liver disease"
                ]
                2 => array:2 [
                  "identificador" => "sec0215"
                  "titulo" => "Digestive diseases"
                ]
              ]
            ]
          ]
        ]
        10 => array:2 [
          "identificador" => "sec0220"
          "titulo" => "New treatments"
        ]
        11 => array:2 [
          "identificador" => "sec0225"
          "titulo" => "Conclusion"
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        12 => array:2 [
          "identificador" => "sec0230"
          "titulo" => "Conflict of interests"
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        13 => array:2 [
          "identificador" => "xack413337"
          "titulo" => "Acknowledgements"
        ]
        14 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2018-07-02"
    "fechaAceptado" => "2018-09-19"
    "PalabrasClave" => array:2 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec1126139"
          "palabras" => array:6 [
            0 => "Osteoporosis"
            1 => "Diagnosis"
            2 => "Treatment"
            3 => "Fracture"
            4 => "Spanish Society of Rheumatology"
            5 => "Recommendations"
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          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec1126140"
          "palabras" => array:6 [
            0 => "Osteoporosis"
            1 => "Diagn&#243;stico"
            2 => "Tratamiento"
            3 => "Fractura"
            4 => "Sociedad Espa&#241;ola de Reumatolog&#237;a"
            5 => "Recomendaciones"
          ]
        ]
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    "resumen" => array:2 [
      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objective</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">To update the recommendations on osteoporosis &#40;OP&#41; of the Spanish Society of Rheumatology &#40;SER&#41; based on the best possible evidence&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A panel of nine expert rheumatologists in OP was created&#44; previously selected by the SER through an open call&#46; The phases of the work were&#58; identification of the key areas for updating the previous consensus&#44; analysis and synthesis of the scientific evidence &#40;using the SIGN levels of evidence&#41; and formulation of recommendations based on this evidence and consensus techniques&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">This revision of the recommendations implies an update in the diagnostic evaluation and treatment of OP&#46; It proposes some criteria to consider the high risk of fracture and some indications to start treatment&#46; The recommendations also address issues related to the safety of treatments and the management of special situations such as inflammatory diseases and treatment with glucocorticoids&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">We present an update of SER recommendations on OP&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Objective"
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          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Methods"
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          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Results"
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          3 => array:2 [
            "identificador" => "abst0020"
            "titulo" => "Conclusions"
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      ]
      "es" => array:3 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objetivo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Actualizar las recomendaciones sobre osteoporosis &#40;OP&#41; de la Sociedad Espa&#241;ola de Reumatolog&#237;a &#40;SER&#41; basadas en la mejor evidencia posible&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">M&#233;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Se cre&#243; un panel formado por nueve reumat&#243;logos expertos en OP previamente seleccionados por la SER mediante una convocatoria abierta&#46; Las fases del trabajo fueron&#58; identificaci&#243;n de las &#225;reas claves para la actualizaci&#243;n del consenso anterior&#44; an&#225;lisis y s&#237;ntesis de la evidencia cient&#237;fica &#40;utilizando los niveles de evidencia del SIGN&#41; y formulaci&#243;n de recomendaciones a partir de esta evidencia y de t&#233;cnicas de consenso&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Esta revisi&#243;n de las recomendaciones comporta una actualizaci&#243;n en la evaluaci&#243;n diagn&#243;stica de la OP y de su tratamiento&#46; Propone unos criterios para considerar alto riesgo de fractura y unas indicaciones para iniciar tratamiento&#46; Las recomendaciones abordan tambi&#233;n cuestiones relativas a la seguridad de los tratamientos y al manejo de situaciones especiales como las enfermedades inflamatorias y el tratamiento con glucocorticoides&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Se presenta la actualizaci&#243;n de las recomendaciones SER sobre OP&#46;</p></span>"
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            "identificador" => "abst0025"
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          2 => array:2 [
            "identificador" => "abst0035"
            "titulo" => "Resultados"
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          3 => array:2 [
            "identificador" => "abst0040"
            "titulo" => "Conclusiones"
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      ]
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    "NotaPie" => array:1 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0015">Please cite this article as&#58; Naranjo Hern&#225;ndez A&#44; D&#237;az del Campo Fontecha P&#44; Aguado Ac&#237;n MP&#44; Arboleya Rodr&#237;guez L&#44; Casado Burgos E&#44; Casta&#241;eda S&#44; et al&#46; Recomendaciones de la Sociedad Espa&#241;ola de Reumatolog&#237;a sobre osteoporosis&#46; Reumatol Clin&#46; 2019&#59;15&#58;188&#8211;210&#46;</p>"
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            "apendice" => "<p id="par1305" class="elsevierStylePara elsevierViewall"><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></p>"
            "etiqueta" => "Annex 1"
            "titulo" => "Levels of evidence and SIGN recommendations"
            "identificador" => "sec0235"
          ]
        ]
      ]
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        "figura" => array:1 [
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        "descripcion" => array:1 [
          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Recommendations for initiating treatment for the prevention of fractures in patients with osteoporosis or risk of osteoporosis&#46;</p>"
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          "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Recommendations to initiate prophylaxis or Op treatment in patients who will receive glucocorticoids in the following 3 months&#46;</p>"
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        "etiqueta" => "Table 1"
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          "leyenda" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">BMD&#58; bone mineral density&#59; FRAX<span class="elsevierStyleSup">&#174;</span>&#58; Fracture Risk Assessment&#59; AL&#58; agreement level&#59; RR&#58; Recommendation rating &#40;see <a class="elsevierStyleCrossRef" href="#sec0235">Appendix 1</a>&#41;&#46;</p>"
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                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Recommendations&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">RR&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">AL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">Diagnosis and evaluation</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Recommendation&#58; It is recommended that fragility fracture risk assessment should not be based exclusively on the measurement of BMD but should also take into account clinical risk factors&#46;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Recommendation&#58; The use of the FRAX</span><span class="elsevierStyleSup"><span class="elsevierStyleItalic">&#174;</span></span><span class="elsevierStyleItalic">&#44; tool is recommended&#44; with or without BMD&#44; to assess fracture risk&#46;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8730;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">78&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Recommendation&#58; The classification of patients into high fracture risk is recommended when the risk quantified by FRAX</span><span class="elsevierStyleSup"><span class="elsevierStyleItalic">&#174;</span></span><span class="elsevierStyleItalic">for hip fracture is &#8805;3&#37;&#46;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8730;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Recommendation&#58; To classify high risk patients using FRAX</span><span class="elsevierStyleSup"><span class="elsevierStyleItalic">&#174;</span></span><span class="elsevierStyleItalic">for primary fracture it is recommended that the threshold used is &#8805;10&#37; without BMD or &#8805;7&#46;5&#37; with BMD&#46;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8730;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">78&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Recommendation&#58; the use of densitometry is recommended in the following cases&#58;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">D</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>1&#46; Fragility fracture&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>2&#46; Presence of two or more high fracture risk factors&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>3&#46; FRAX<span class="elsevierStyleSup">&#174;</span> for primary fracture &#8805;5&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">78&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>4&#46; Treatment with aromatase inhibitor drugs&#44; antiandrogen drugs and glucocorticoids&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>5&#46; Disease associated with secondary OP&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Recommendation&#58; A basic analytical study is recommended to rule out secondary causes of osteoporosis&#46;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8730;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Recommendation&#58; The routine example of bone turnover markers is not established&#46; However&#44; they could be considered in the initial assessment and in follow-up of patients with osteoporosis&#46;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">89&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Recommendation&#58; Assessment of the presence of vertebral fractures is recommended in the high fracture risk patient or the patient with osteoporosis when kyphosis or significant height loss is perceived and when there is back pain or low back pain of recent onset&#46;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">D&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">Treatment</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Recommendation&#58; A healthy lifestyle is recommended for the prevention of primary and secondary osteoporosis and fractures&#44; including a balanced diet and regular physical exercise&#44; avoidance of tobacco&#44; limitation of alcohol consumption and the use of preventative measures for falls&#46;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8730;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Recommendation&#58; A daily intake of calcium between 1000 and 1200</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">mg&#44; most of which should be included in the regular diet&#46;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">D&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Recommendation&#58; The daily intake of 800</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">UI of vitamin is recommended in the following cases&#58;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">D</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="6" align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100&#37;</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>1&#46; Patients with osteoporosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>2&#46; People over 65 years of age with fracture risk&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>3&#46; People with vitamin D deficiency&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>4&#46; People with limited exposure to sunlight&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>5&#46; People with inadequate calcium intake &#40;under 700&#8211;800<span class="elsevierStyleHsp" style=""></span>mg per day&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Recommendation&#58; Initiation of pharmacological treatment is recommended to reduce the risk of osteoporotic fracture in the following situations&#46;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="8" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8730;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>1&#46; Fragility fracture of vertebra or hip in patients &#62;50 years of age&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>2&#46; Other fragility fractures in patients &#62;50 years of age and with low bone mass &#40;<span class="elsevierStyleItalic">T</span>-score &#60;&#8722;1 SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">89&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>3&#46; OP defined by <span class="elsevierStyleItalic">T</span>-score &#8804;&#8722;25 SD in spine&#44; femoral neck or hip&#44; always considering age&#44; BMD figures and other risk factors&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>4&#46; Patients with high risk of hip fracture according to FRAX<span class="elsevierStyleSup">&#174;</span> with BMD &#8805;3&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>5&#46; Men being treated with androgen deprivation and <span class="elsevierStyleItalic">T</span>-score &#8804;&#8722;2&#46;5 SD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>6&#46; Women in treatment with aromatase inhibitors and <span class="elsevierStyleItalic">T</span>-score &#8804;&#8722;2 SD or with a <span class="elsevierStyleItalic">T</span>-score &#60;&#8722;1&#46;5 SD and an additional risk factor&#44; or with &#8805;2 risk factors without BMD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">78&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>7&#46; Patients who are going to receive glucocorticoids for over 3 months in the following cases&#58; &#40;a&#41; initial dose &#8805;30<span class="elsevierStyleHsp" style=""></span>mg&#47;day of prednisone&#59; &#40;b&#41; postmenopausal women and men &#62;50 years of age with dose &#8805;5<span class="elsevierStyleHsp" style=""></span>mg&#47;day and previous fragility fracture or <span class="elsevierStyleItalic">T</span>-score &#8804;&#8722;1&#46;5 SD or high risk of fracture&#58; FRAX<span class="elsevierStyleSup">&#174;</span> for hip &#8805;3&#37; or for primary fracture &#8805;10&#37; without BMD or &#8805;7&#46;5&#37; with BMD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Recommendation&#58; When selecting treatment&#44; among other factors&#44; it is recommended to consider&#58;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="9" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8730;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="9" align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100&#37;</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>1&#46; The efficacy and safety of the drugs&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>2&#46; The cost&#47;effectiveness ratio&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>3&#46; The BMD value&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>4&#46; The presence of fractures&#44; particularly vertebral or multiple fragility fractures&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>5&#46; Previous treatments and adherence to the same&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>6&#46; Age&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>7&#46; Comorbidities and polymedication&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>8&#46; Limitations for oral administration&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Recommendation&#58; It is recommended that fracture risk be reassessed after 5 years of treatment with oral bisphosphonates or after 3 years of treatment with zoledronic acid&#46;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">D&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Recommendation&#58; When treatment with denosumab is suspended an alternative treatment for the osteoporosis must be considered&#46;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">D&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Recommendation&#58; In high fracture risk patients&#44; including those with previous fragility fracture&#44; or with a T-score of proximal femur &#60;&#8722;&#46;5 SD&#44; it is not recommended to discontinue the osteoporosis treatment&#46;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">D&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">89&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Recommendation&#58; A periodical clinical assessment is recommended to confirm adherence to and efficacy of treatment&#44; incidence of fractures and the possible appearance of adverse effects&#46;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8730;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Recommendation&#58; If the patient with OP has been subjected to any invasive dental procedure &#40;extraction or implant&#41; it is advised to postpone antiresorptive treatment initiation until the surgical wound has completely healed&#46;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">D&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Recommendation&#58; In patients treated with antiresorptives who are going to have a dental procedure it is not recommended to discontinue treatment with BP or denosumab&#46; If risk factors additional to osteonecrosis of the jawbones exist or the surgical procedure is to be extensive temporary discontinuation of treatment with BP may be considered&#46;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">D&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">78&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Recommendation&#58; In patients with high fracture risk and prolonged treatment with bisphosphonates &#40;&#62;5 years for orals or &#62;3 years for intravenous&#41; it is recommended not to suspend treatment&#44; since the risk of atypical femur fracture is very low and the benefits of fracture reduction greatly outweigh the risk of atypical fracture&#46;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">D&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">Special situations</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Recommendation&#58; It is recommended that all patients &#8805;50 years of age with a recent fragility fracture be assessed systematically to prevent further fractures&#46;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">D&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Recommendation&#58; The treatment of choice for an acute vertebral fracture is rest&#44; rapidly scaled analgesics to control pain&#44; and if necessary the use of a brace&#46;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8730;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Recommendation&#58; Vertebroplasty and kyphoplasty are recommended for the treatment of vertebral fracture only in cases of serious refractory pain on a WHO analgesic scale&#44; including opiates&#46;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">D&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Recommendation&#58; In patients who receive or who are going to receive treatment with glucocorticoids fracture risk must be assessed and the initiation of treatment for osteoporosis as soon as possible&#46;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">D&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Recommendation&#58; It is recommended that pharmacological treatment be initiated to prevent OP in patients who are going to receive glucocorticoids for over 3 months in the following cases&#58;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="9" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">D</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>1&#46; Patients with an initial dose &#8805;30<span class="elsevierStyleHsp" style=""></span>mg&#47;day of prednisone&#46; In these cases it is recommended that treatment be imitated for OP immediately&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>2&#46; Postmenopausal women and men &#62;50 years of age with a prednisone dose &#8805;5<span class="elsevierStyleHsp" style=""></span>mg&#47;day who also present with some of the following conditions&#58;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>a&#41; Previous fragility fracture&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">89&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>b&#41; Low BMD &#40;<span class="elsevierStyleItalic">T</span>-score &#8804;&#8722;1&#46;5 SD in spine or hip&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">78&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>c&#41; High fracture risk&#58; FRAX<span class="elsevierStyleSup">&#174;</span>for hip &#8805;3&#37; or for primary fracture &#8805;10&#37; without BMD or &#8805;7&#46;5&#37; with BMD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>3&#46; Premenopausal women and men &#60;50 years of age and daily dose &#8805;7&#46;5<span class="elsevierStyleHsp" style=""></span>mg&#47;of prednisone who also present with one of the following conditions&#58;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">78&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>a&#41; Previous fragility fracture&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">78&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>b&#41; Low BMD &#40;<span class="elsevierStyleItalic">Z</span>-score &#8804;&#8722;3 SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Recommendation&#58; It is advisable to assess the risk of fracture and consider performing DXA in patients with rheumatoid arthritis&#44; systemic lupus erythematosus and ankylosing spondylitis especially those over 50 years of age and who are being treated with glucocorticoids or with a severe or evolved disease&#46;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8730;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Recommendation&#58; The study of the causes of secondary osteoporosis in all men with low bone mass or fragility fracture is recommended&#46;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">D&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Recommendation&#58; It is recommended that a study of secondary osteoporosis causes be made in all premenopausal women with a low bone mass or with a fragility fracture&#46;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8730;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2064904.png"
              ]
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          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">SER recommendations on osteoporosis&#46;</p>"
        ]
      ]
      3 => array:8 [
        "identificador" => "tbl0020"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at2"
            "detalle" => "Table "
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        "tabla" => array:2 [
          "tablatextoimagen" => array:1 [
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              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Higher risk &#40;relative risk</span> &#8805;<span class="elsevierStyleItalic">2&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Over 65 years of age&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Low weight&#58; body mass index &#60;20<span class="elsevierStyleHsp" style=""></span>kg&#47;m<span class="elsevierStyleSup">2</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Personal history of fragility fracture&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Maternal history of femur fracture&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Glucocorticoids &#40;&#62;5<span class="elsevierStyleHsp" style=""></span>mg&#47;day of prednisone or equivalent for &#62;3 months&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>More than 2 falls in the last year&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Moderate risk &#40;relative risk between 1and 2&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Active smoker&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Consumes &#62;3<span class="elsevierStyleHsp" style=""></span>units of alcohol per day<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Early menopause &#40;&#60;45 years of age&#41;&#44; primary and secondary amenorrhea&#44; hypogonadism in the male&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Diseases which may reduce BMD&#58; rheumatoid arthritis and other inflammatory arthropathies&#44; intestinal pathology&#44; celiac disease&#44; malabsorption&#44; hepatopathies&#44; hyperparathyroidism&#44; anorexia and bulimia&#44; solid organ transplant&#44; etc&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Drugs with the ability to reduce BMD&#47;increases the risk of fractures&#58; hydantoins&#44; antiretrovirals&#44; anticonvulsants&#44; aromatase inhibitors&#44; androgen deprivation drugs&#44; etc&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Conditions related to falls&#58; eye conditions&#44; neurological diseases &#40;stroke&#44; Parkinson&#41;&#44; use of psychodrugs&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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                0 => "xTab2064905.png"
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          "notaPie" => array:1 [
            0 => array:3 [
              "identificador" => "tblfn0005"
              "etiqueta" => "a"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0005">One unit of alcohol is equal to 200<span class="elsevierStyleHsp" style=""></span>ml of beer or 100<span class="elsevierStyleHsp" style=""></span>ml of wine or 25<span class="elsevierStyleHsp" style=""></span>ml of a spirit&#46;</p>"
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Clinical fracture risk factors&#46;</p>"
        ]
      ]
      4 => array:8 [
        "identificador" => "tbl0025"
        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at3"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cover nutritional requirements with a healthy diet which includes an adequate intake of proteins &#40;0&#46;8<span class="elsevierStyleHsp" style=""></span>g per kilo of body weight&#41;&#44; calcium&#44; fruit and vegetables&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Limit caffeine intake&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Prudent exposure to sunlight&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Avoid consumption of tobacco and limited intake of alcohol to under 3 units per day<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Encourage physical activity with regular exercise both own weight bearing &#40;examine&#58; walking&#44; dancing&#44; practising taichi 30&#8211;40<span class="elsevierStyleHsp" style=""></span>min per session&#41; and muscle and postural strengthening&#44; 3&#8211;4 days per week&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2064903.png"
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          ]
          "notaPie" => array:1 [
            0 => array:3 [
              "identificador" => "tblfn0010"
              "etiqueta" => "a"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0010">One unit of alcohol is equal to 200<span class="elsevierStyleHsp" style=""></span>ml of beer or 100<span class="elsevierStyleHsp" style=""></span>ml of wine or 25<span class="elsevierStyleHsp" style=""></span>ml of a spirit&#46;</p>"
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">Main habits of a healthy lifestyle&#46;<a class="elsevierStyleCrossRefs" href="#bib1260"><span class="elsevierStyleSup">53&#8211;57</span></a></p>"
        ]
      ]
      5 => array:8 [
        "identificador" => "tbl0030"
        "etiqueta" => "Table 4"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at4"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">ND&#58; not demonstrated&#59; PH&#58; post hoc analysis by subgroups &#40;designed after knowledge of the trial outcome&#41;&#59; SG&#58; subgroup analysis designed prior to knowing the trial outcome&#59; SI&#58; ITT &#40;intention to try&#41; analysis&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="3" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Vertebral</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="2" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Non vertebral</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="2" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Hip</th></tr><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Osteopenia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Osteoporosis &#40;no previous vertebral fracture&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Established Osteoporosis &#40;with previous vertebral fracture&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Osteoporosis &#40;no previous vertebral fracture&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Established Osteoporosis &#40;with previous vertebral fracture&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Osteoporosis &#40;no previous vertebral fracture&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Established Osteoporosis &#40;with previous vertebral fracture&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Alendronic acid<a class="elsevierStyleCrossRefs" href="#bib1410"><span class="elsevierStyleSup">83&#44;84</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">SI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">SI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Risedronic acid<a class="elsevierStyleCrossRefs" href="#bib1420"><span class="elsevierStyleSup">85&#44;86</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">PH&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Zoledronic acid<a class="elsevierStyleCrossRef" href="#bib1430"><span class="elsevierStyleSup">87</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Denosumab<a class="elsevierStyleCrossRef" href="#bib1435"><span class="elsevierStyleSup">88</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Teriparatide<a class="elsevierStyleCrossRef" href="#bib1440"><span class="elsevierStyleSup">89</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Ibandronic acid<a class="elsevierStyleCrossRef" href="#bib1445"><span class="elsevierStyleSup">90</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PH&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Bazedoxifene<a class="elsevierStyleCrossRef" href="#bib1455"><span class="elsevierStyleSup">92</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">SI&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">PH&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PH&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "leyenda" => "<p id="spar0100" class="elsevierStyleSimplePara elsevierViewall">SD&#58; standard deviation&#59; RF&#58; risk factor&#59; Fr&#58; fracture&#59; NNT&#58; necessary number to treat&#59; ARR&#58; absolute risk reduction&#59; RRR&#58; relative risk reduction&#59; <span class="elsevierStyleItalic">T</span>&#58; <span class="elsevierStyleItalic">T</span>-score&#46;</p>"
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                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Study &#40;duration&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Baseline risk profile&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Mean age &#40;years&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">RRR &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">RRA &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">NNT&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">FIT-1<a class="elsevierStyleCrossRef" href="#bib1410"><span class="elsevierStyleSup">83</span></a> &#40;3 years&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Alendronic acid&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Vertebral Fr&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">71&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">47&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">FIT-2<a class="elsevierStyleCrossRef" href="#bib1415"><span class="elsevierStyleSup">84</span></a> &#40;3 years&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Alendronic acid&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Without Vertebral Fr&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">68&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">44&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">60&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">BONE<a class="elsevierStyleCrossRef" href="#bib1445"><span class="elsevierStyleSup">90</span></a> &#40;3 years&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ibandronic acid&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Vertebral Fr&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">69&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">62&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">27&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">VERT NA<a class="elsevierStyleCrossRef" href="#bib1420"><span class="elsevierStyleSup">85</span></a> &#40;3 years&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Risedronic acid&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Vertebral Fr&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">69&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">41&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">VERT MN<a class="elsevierStyleCrossRef" href="#bib1425"><span class="elsevierStyleSup">86</span></a> &#40;3 years&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Risedronic acid&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Vertebral Fr&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">71&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">49&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">HORIZON<a class="elsevierStyleCrossRef" href="#bib1430"><span class="elsevierStyleSup">87</span></a> &#40;3 years&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Zoledronic acid</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">T</span> &#60;&#8722;1&#46;5 SD<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>Vertebral Fr&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">73</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">70</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">or&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">T</span> &#60;&#8722;2&#46;5 SD<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>Vertebral Fr&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">MORE<a class="elsevierStyleCrossRef" href="#bib1450"><span class="elsevierStyleSup">91</span></a> &#40;3 years&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Raloxifene</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Vertebral Fr or&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">67</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">35</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;5</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">16</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">T</span> &#60;&#8722;2&#46;5 SD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Silverman et al&#46;<a class="elsevierStyleCrossRef" href="#bib1455"><span class="elsevierStyleSup">92</span></a> &#40;3 years&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Bazedoxifene</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sin Vertebral Fr <span class="elsevierStyleItalic">T</span> &#60;&#8722;2&#46;5 SD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">67</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">38</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">82</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">and &#62;&#8722;4 SD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">With Vertebral Fr <span class="elsevierStyleItalic">T</span> &#62;&#8722;4 SD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">FPT<a class="elsevierStyleCrossRef" href="#bib1440"><span class="elsevierStyleSup">89</span></a> &#40;2 years&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Teriparatide&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Vertebral Fr&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">70&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">65&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">FREEDOM<a class="elsevierStyleCrossRef" href="#bib1435"><span class="elsevierStyleSup">88</span></a> &#40;3 years&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Denosumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">T</span> between &#8722;2&#46;5 and &#8722;4 SD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">72&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">67&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">4&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Study &#40;duration&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Drug&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Baseline risk profile&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Mean age &#40;years of age&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">RRR &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">ARR &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">NNT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">FIT-1 &#40;3 years&#41;<a class="elsevierStyleCrossRef" href="#bib1410"><span class="elsevierStyleSup">83</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Alendronic acid&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Vertebral Fr&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">71&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">FIT-2 &#40;3 years&#41;<a class="elsevierStyleCrossRef" href="#bib1415"><span class="elsevierStyleSup">84</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Alendronic acid&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sin Vertebral Fr&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">68&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">VERT NA &#40;3 years&#41;<a class="elsevierStyleCrossRef" href="#bib1420"><span class="elsevierStyleSup">85</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Risedronic acid&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Vertebral Fr&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">69&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">40&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">31&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">VERT MN &#40;3 years&#41;<a class="elsevierStyleCrossRef" href="#bib1425"><span class="elsevierStyleSup">86</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Risedronic acid&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Vertebral Fr&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">71&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">33&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">HIP &#40;3 years&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Risedronic acid</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Group 1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">74</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;8</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">55</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">T</span> &#60;&#8722;4 SD &#60;&#8722;3 SD and RF&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">HORIZON &#40;3 years of age&#41;<a class="elsevierStyleCrossRef" href="#bib1430"><span class="elsevierStyleSup">87</span></a></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Zoledronic acid</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">T</span> &#60;&#8722;1&#46;5 SD<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>Vertebral Fr&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">73</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">28</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;7</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">37</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">or&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">T</span> &#60;&#8722;2&#46;5 SD<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>Vertebral Fr&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">HORIZON-R<a class="elsevierStyleCrossRef" href="#bib1460"><span class="elsevierStyleSup">93</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Zoledronic acid&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Hip Fr&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">75&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">27&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">30&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">FPT &#40;2 years&#41;<a class="elsevierStyleCrossRef" href="#bib1440"><span class="elsevierStyleSup">89</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Teriparatide&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Vertebral Fr&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">70&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">35&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">34&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">FREEDOM &#40;3 years&#41;<a class="elsevierStyleCrossRef" href="#bib1435"><span class="elsevierStyleSup">88</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Denosumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">T</span> between &#8722;2&#46;5 and &#8722;4 SD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">72&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">66&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "leyenda" => "<p id="spar0120" class="elsevierStyleSimplePara elsevierViewall">SD&#58; standard deviation&#59; RF&#58; risk factor&#59; Fr&#58; fracture&#59; NNT&#58; necessary number to treat&#59; ARR&#58; absolute risk reduction&#59; RRR&#58; relative risk reduction&#59; <span class="elsevierStyleItalic">T</span>&#58; <span class="elsevierStyleItalic">T</span>-score&#46;</p>"
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                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Study &#40;duration&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Drug&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Baseline risk profile&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Age &#40;years&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">RRR &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">ARR &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">NNT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">FIT-1<a class="elsevierStyleCrossRef" href="#bib1410"><span class="elsevierStyleSup">83</span></a> &#40;3 years&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Alendronic acid&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Vertebral Fr&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">71&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">51&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">90&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">HIP<a class="elsevierStyleCrossRef" href="#bib1465"><span class="elsevierStyleSup">94</span></a> &#40;3 years&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Risedronic acid</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Group 1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">74</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">40</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;3</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">77</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">T</span> &#60;&#8722;4 SD or &#60;&#8722;3 SD and RF&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">HORIZON<a class="elsevierStyleCrossRef" href="#bib1430"><span class="elsevierStyleSup">87</span></a> &#40;3 years&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Zoledronic acid</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Vertebral Fr<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">T</span>&#60;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="5" align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">73</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="5" align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">41</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="5" align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;9</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="5" align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">109</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8722;1&#46;5 SD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">or&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">T</span> &#60;&#8722;2&#46;5 SD<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>Fr&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">vertebral&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">FREEDOM<a class="elsevierStyleCrossRef" href="#bib1435"><span class="elsevierStyleSup">88</span></a> &#40;3 years&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Denosumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">T</span> &#60;&#8722;2&#46;5 and &#62;&#8722;4 SD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">72&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">39&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">230&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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          "leyenda" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Studies classified as 1&#8722; and 2&#8722; should not be used in the production of recommendations due to their high possibility of bias&#46;</p>"
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                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="2" align="center" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Levels of evidence</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">1&#43;&#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">High quality meta-analysis&#44; systematic reviews of clinical trials or high quality clinical trials with very low risk of bias&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Well executed meta-analysis&#44; systematic reviews of clinical trials or well executed clinical trials with low risk of bias&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#8722;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Meta-analysis&#44; systematic reviews of clinical trials or clinical trials with high risk of bias&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#43;&#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Systematic reviews of high quality cohort studies or cases and controls&#46; Cohort studies or case and control studies with a very low risk of bias and high probability of establishing a causal relationship&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Well executed cohort studies or case and control studies with low risk of bias and a moderate probability of establishing a causal relationship&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#8722;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cohort studies or case and control studies with high risk of bias and significant risk that there will be no causal relationship&#46;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">Non analytical studies&#44; such as case reports and case series&#46;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">Expert opinions&#46;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">A volume of scientific evidence composed by studies classified as 2&#43;&#43;&#44; directly applicable to the target population of the guide and which show major concordance between them&#59; or scientific evidence extrapolated from studies classified as 1&#43;&#43; or 1&#43;&#46;&nbsp;\t\t\t\t\t\t\n
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        "texto" => "<p id="par1300" class="elsevierStylePara elsevierViewall">The group of experts of this study wish to express their gratitude to Mercedes Guerra Rodr&#237;guez&#44; the SER documentalist for her collaboration in search strategies and to Dr&#46; Hye Sang Park for her collaboration in the RS report reviews&#46; They also wish to thank Dr&#46; Federico Diaz Gonz&#225;lez&#44; director of the SER Research Unit&#44; for his participation in the final manuscript review and for contributing to maintaining the independence of this document&#46;</p>"
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Article information

ISSN: 21735743
Original language: English

DOI:10.1016/j.reumae.2018.09.011

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