Threshold based on bone mineral density for therapeutic decision-making in postmenopausal women and men over 50 years old under glucocorticoid therapy

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Posadas, Buenos Aires, Argentina" "etiqueta" => "f" "identificador" => "aff0030" ] 6 => array:3 [ "entidad" => "Hospital Italiano de Buenos Aires, Buenos Aires, Argentina" "etiqueta" => "g" "identificador" => "aff0035" ] 7 => array:3 [ "entidad" => "Hospital Privado de Rosario (Grupo Gamma), Rosario, Argentina" "etiqueta" => "h" "identificador" => "aff0040" ] 8 => array:3 [ "entidad" => "Instituto de Rehabilitación Psicofísica (IREP), Buenos Aires, Argentina" "etiqueta" => "i" "identificador" => "aff0045" ] 9 => array:3 [ "entidad" => "Ceim Investigaciones Médicas, Buenos Aires, Argentina" "etiqueta" => "j" "identificador" => "aff0050" ] 10 => array:3 [ "entidad" => "Hospital Provincial del Centenario, Rosario, Argentina" "etiqueta" => "k" "identificador" => "aff0055" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Umbral densitométrico de densidad mineral ósea para considerar tratamiento en pacientes mujeres posmenopáusicas y hombres mayores de 50 años en tratamiento con glucocorticoids" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 4168 "Ancho" => 1697 "Tamanyo" => 434551 ] ] "descripcion" => array:1 [ "en" => "Flowcharts of both systematic review." ] ] ] "textoCompleto" => "IntroductionBone mineral density (BMD) measured by dual X-ray absorptiometry (DXA) is the current gold standard reference for the diagnosis of osteoporosis. Since BMD is one of the strongest predictors of fracture risk, many agencies worldwide have adopted BMD-based criteria as intervention thresholds.<a class="elsevierStyleCrossRef" href="#bib0260">1</a> According to existing guidelines for postmenopausal women, a T-score of −2.5 SD or lower is recommended to offer treatment in those patients without fragility fractures.<a class="elsevierStyleCrossRef" href="#bib0265">2</a> The T-score BMD thresholds might influence current guidance for treatment in patients under glucocorticoid (GC) therapy. Different BMD thresholds were described throughout the time.<a class="elsevierStyleCrossRefs" href="#bib0270">3–9</a> Several differences exist between the 2001 and 2010 American College of Rheumatology (ACR) glucocorticoid-induced osteoporosis (GIO) guidelines. In 2001, the ACR guideline recommended treatment for GIO in any patient with a T-score below −1.0. On the other hand, in 2010 the treatment was suggested considering the low, moderate, or high-risk of fracture. The ASBMR-PPC (American Society for Bone and Mineral Research-Professional Practice Committee) also stratified postmenopausal women and men≥50 years into low, medium, and high risk of fracture according to FRAX score. For patients who had low risk but have an indication for prednisone >7.5mg/day, the recommendation is to indicate treatment but for those with lower GC doses, the suggestion is to monitor the patient with BMD.<a class="elsevierStyleCrossRef" href="#bib0285">6</a> In 2012, the IOF-ECTS GIO Guidelines Working Group defined a BMD T-score lower than −1.5 as one of the indications for bone-protective therapy in postmenopausal women and men ≥50 years under GC therapy.<a class="elsevierStyleCrossRef" href="#bib0290">7</a> The Japanese guidelines also consider it as a cut-off value of BMD in around 80% of the young adult population.<a class="elsevierStyleCrossRef" href="#bib0305">10</a> The ACR guideline 2017 recommended initial pharmacologic treatment in adults≥40 years of age who are at moderate-to-high risk of fracture considering high-risk to those with T-score≤−2.5, by FRAX GC-adjusted or with a prior fragility fracture. Recently, the 2020 GIO Brazilian guidelines recommended a T-score≤−1.89 for treatment in men.<a class="elsevierStyleCrossRef" href="#bib0295">8</a> Consequently, there is no international consensus regarding the BMD cut-off for diagnosis and treatment in GIO.Therefore, in the context of the development of Argentine guidelines for prevention and treatment of GIO, a working group on behalf of three scientific societies from Argentina: AAOMM (Asociación Argentina de Osteología y Metabolismo Mineral – Argentine Association of Osteology and Mineral Metabolism), SAO (Sociedad Argentina de Osteoporosis – Argentine Osteoporosis Society) and SAR (Sociedad Argentina de Reumatología – Argentine Society of Rheumatology) was convened to identify areas of consensus among a panel of experts, with the aim of discussing the available data for the threshold based on BMD for therapeutic decision-making in postmenopausal and men≥50 years under GC therapy. In the absence of a consensus about a cut-off for the diagnosis of GIO, there is a risk of not identifying those patients who, under GC therapy, are at risk of fragility fracture.ObjectiveThe overall aim of this study was to find a threshold according to the reported evidence to be able to help in the treatment decision in the population under GC therapy.MethodsDevelopment teamsThis work involved a working group on behalf of three scientific societies from Argentina: AAOMM, SAO and SAR. An equal number of participants was selected by each society according to its expertise.The first team was formed by specialists (rheumatologists, endocrinologists, internists, physiatrists) with expertise and clinical experience in treating GIO and bone diseases. The second team was constituted by a methodology group who coordinated and supervised each stage of the work and conducted the literature search and data abstraction, rated the quality of evidence, analyzed the data, and created the tables of summary of findings. In the framework of two virtual meetings, the methodology and summary of findings of the two systematic reviews were shown to the voting expert panel who discuss about the threshold based on BMD for therapeutic decision-making in postmenopausal and men≥50 years under GC therapy. The voting expert panel voted both diagnostic questions requiring 70% agreement among the voting members. Diagnostic questions: 1. What was the densitometric threshold used as inclusion criteria in the population treated with GC in the trials that studied drugs for GIO? 2. What would be the best densitometric threshold that discriminates among fractures and non fractures in patient under GC treatment?Systematic reviewsTwo systematic reviews were performed (<a class="elsevierStyleCrossRef" href="#sec0095">Appendix 1</a>). In the first systematic review the literature was searched for key terms until October 2020, using the databases of MEDLINE (National Library of Medicine) (<a href="https://pubmed.ncbi.nlm.nih.gov/">https://pubmed.ncbi.nlm.nih.gov/</a>), Cochrane Library (<a href="https://www.cochranelibrary.com/">https://www.cochranelibrary.com/</a>) and LILACS (<a href="https://lilacs.bvsalud.org/es/">https://lilacs.bvsalud.org/es/</a>), and grey literature in the last 5 years. This review was performed in the context of the development of Argentine guidelines for prevention and treatment of GIO under PICO structure. In this first review, the focus was to evaluate the T-score cut-off used in the trials that evaluated pharmacological intervention in GIO. In the second systematic review, the literature was searched for key terms until February 2022 and aimed to search for evidence about the BMD T-score threshold that discriminates between fractured and non-fractured populations. An expert panel reviewed the included studies selected in both systematic reviews.Eligibility criteriaWe included randomized controlled trials, non-randomized trials, post hoc analysis and pooled analysis in postmenopausal women and men older than 50 years old, in which the T-score BMD baseline was reported studying a pharmacological treatment in patients under GC therapy (≥5mg/day prednisolone or equivalent) regardless of GC administration time. T-scores BMD in the lumbar spine (LS) or total hip (TH), thresholds T-scores BMD values were considered as outcomes. Only articles in English, Portuguese and Spanish were included.Case reports, reviews, letters to the editor, animal studies, editorials, commentaries, other languages than the described previously, and if identical data were re-analyzed were considered as exclusion criteria.Study selectionRayyan software (<a href="https://rayyan-prod.qcri.org/welcome">https://rayyan-prod.qcri.org/welcome</a>) was used to screen the literature search results. Two independent reviewers performed the title and abstract screening and then underwent full-text screening. A third reviewer was included in case of conflicts.The data extraction and processing were obtained by two authors independently using a standardized data extraction: authors, study design, participants, age of participants, time and dose of GC, diagnostic used for osteoporosis, baseline T-score value in each group, intervention, comparator.The quality assessment and publication bias of randomized controlled trials were judged using the Cochrane risk of bias tool (<a href="http://handbook.cochrane.org/">http://handbook.cochrane.org/</a>). For non-randomized controlled trials, the assessment was performed using the Newcastle–Ottawa scale (NOS).<a class="elsevierStyleCrossRef" href="#bib0310">11</a> For cross-sectional studies, we used a modified version of NOS and studies that received at least seven stars (maximum of ten) were classified as good quality. The PRISMA-P guideline was used to prepare this systematic review.<a class="elsevierStyleCrossRefs" href="#bib0315">12,13</a>ResultsQualitative synthesis. Description of studiesThe studies were divided into two parts according to each search: Part 1 included the trials of drugs used in GIO, while Part 2 included BMD thresholds for fractured and non-fractured patients’ discrimination under GC therapy. The flowcharts of both systematic reviews are shown in <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>, and the quality assessment of the studies is in <a class="elsevierStyleCrossRef" href="#sec0095">Appendix 2</a>.<elsevierMultimedia ident="fig0005"></elsevierMultimedia>Part 1In this first revision, a total of 1214 selected articles were found. A total of 31 articles were included for qualitative synthesis and we stratify the trials according to the densitometric T-score used as inclusion criteria in each trial.<a class="elsevierStyleCrossRefs" href="#bib0325">14–44</a>The summary of the studies characteristics is shown in <a class="elsevierStyleCrossRef" href="#sec0095">Appendix 3</a>. The 93.7% of the trials included patients regardless of the densitometric T-score or in the range of osteopenia (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>Part 2In this second revision a total of 54 selected articles were found and 4 articles were included.<a class="elsevierStyleCrossRefs" href="#bib0480">45–48</a> More than 80% of the T-scores were between the −1.6 and −2.0 range (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).<elsevierMultimedia ident="tbl0010"></elsevierMultimedia>Expert panel consensusAfter analyzing the evidence from both systematic reviews, the expert panel discussed in meetings in the framework of a working group with experts in bone diseases. The expert panel voted on the threshold of the BMD T-score that best identifies fractured from the non-fractured population. Taking into account that more than 90% of the trials about GIO included patients regardless of the densitometric T-score or in the range of osteopenia, and more than 80% of the T-scores that discriminates between fractured and non-fractured patients are within −1.6 and −2.0, the voting was performed among this range.With an agreement over 80% of the voting expert panel, a T-score≤−1.7 was considered the most appropriate for treatment in postmenopausal women and men older than 50 years under GC therapy.DiscussionThe T-score BMD thresholds might influence current guidance for treatment in patients under GC treatment. Several published guidelines for GIO management demonstrate large differences in the thresholds in patients under GC treatment as were previously detailed. In GIO there is no international consensus regarding the most appropriate BMD threshold for treatment. Therefore, we considered conducting this systematic review in the context of the development of Argentine guidelines for prevention and treatment of glucocorticoid-induced osteoporosis by 3 scientific societies from Argentina to determine the most appropriate BMD T-score threshold to help in the GIO treatment decision.As far as we know, the thresholds are noy ideal from every perspective and there is no T-score BMD threshold gold standard established by international consensus in GIO. At the same time, the fracture incidence differs markedly in different regions of the world, accordingly to ethnicity among other variables.<a class="elsevierStyleCrossRef" href="#bib0500">49</a> Despite it being suggested that each country should determine their own intervention thresholds, based on fracture incidence, availability of resources, and economic considerations, these data are not always available. Therefore, the fracture risk assessment tool (FRAX) was developed to estimate the 10-year probability of fractures.<a class="elsevierStyleCrossRef" href="#bib0505">50</a> Dawson-Hughes et al. identified cost-effective intervention thresholds based on 10-year absolute hip fracture risk. With BMD in osteopenia levels (T-score −2.0) plus a clinical risk factor, the absolute fracture probability estimate meets or exceeds the 3% cost-effectiveness threshold in all instances.<a class="elsevierStyleCrossRef" href="#bib0510">51</a>Previous studies have evaluated BMD thresholds for discrimination of fractured and non-fractured patients under GC therapy.<a class="elsevierStyleCrossRefs" href="#bib0480">45–48</a> Kaji et al. analyzed the threshold of BDM for vertebral fracture in Japanese female patients with GIO.<a class="elsevierStyleCrossRef" href="#bib0495">48</a> The cut-off values of BMD which discriminates patients with vertebral fractures from those without vertebral fractures were higher in patients with GC treatment. They found a cut-off for vertebral fracture of −1.88 in lumbar spine BMD (sensitivity and specificity 61.5%) and −1.67 in femoral neck BMD (sensitivity and specificity 70.9%). Nawata et al., in the context of the GIO Japanese guidelines, described the results of a longitudinal study in which the BMD T-score cut-off was discriminated between fractures and non-fractures.<a class="elsevierStyleCrossRef" href="#bib0485">46</a> Considering the whole GC treated group (n=692), the cut-off found was a T-score of −1.97. Van Staa TP et al., after analyzing data from 2 large, prospective, randomized controlled trials (n=306) showed that the daily GC dose, and not the cumulative dose, is a strong predictor of the risk of vertebral fracture in postmenopausal women under GC therapy, at similar baseline levels of BMD. They described a T-score threshold of −1.8 for the lumbar spine and −1.9 for femoral neck BMD.<a class="elsevierStyleCrossRef" href="#bib0480">45</a>In summary, the voting expert panel selected a BMD T-score≤−1.7 as the most appropriate for help in the treatment decision in postmenopausal women and men older than 50 years under GC therapy. This agreement was reached after prolonged discussion and debate. Lower T-scores were not selected because lack of evidence was considered and to avoid overtreatment even when there is not enough data on the different ethnic groups and populations.One of the limitations of this paper is that the analysis is based on indirect data from systematic reviews and most data come from the Japanese population. However, two exhaustive systematic reviews were conducted, addressing the problem from two perspectives as a strength. Therefore, longitudinal studies according to age, gender and ethnicity are needed to identify the optimal BMD threshold.ConclusionsWith an agreement over 80% of the voting expert panel, a T-score≤−1.7 was considered the most appropriate for treatment in postmenopausal women and men older than 50 years under GC therapy. This study could help in the treatment decision in patients under GC therapy without fractures but certainly should consider other concepts as age, sex, fracture history, risk fracture stratification, FRAX, among others.Authors’ contributionMLB: study design and scope of these systematic reviews. MLB, MSL, LFS, EG, MD, AMG, LARS, MDLV: voting expert panel. MLB, AR, LARS, CM, LRB: performed the systematic review. MLB and LRB: drafting of the manuscript. All authors read, discussed, and approved the final manuscript.Financial supportNone.Conflict of interestMaria Lorena Brance received lecture fees from Amgen and Craveri and fees as an advisory board from Amgen. María Silvia Larroudé received lecture fees from Pfizer, Lilly, Amgen, Astrazeneca and Genzyme Sanofi. Evangelina Giacoia received lecture fees and fees as an advisory board from Amgen. María Diehl received research support from Amgen. Ana María Galich received lecture fees from Raffo, Amgen and Eli Lilly. Luis Fernando Somma, Luis Agustín Ramirez Stieben, María Cielo Maher, Maria Celina de la Vega, Ariana Ringer, and Lucas R Brun reported no conflicts of interest." "textoCompletoSecciones" => array:1 [ "secciones" => array:14 [ 0 => array:3 [ "identificador" => "xres1893831" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction and aim" ] 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" => "xpalclavsec1638535" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1893830" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción y 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" => "xpalclavsec1638536" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Objective" ] 6 => array:3 [ "identificador" => "sec0015" "titulo" => "Methods" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0020" "titulo" => "Development teams" ] 1 => array:2 [ "identificador" => "sec0025" "titulo" => "Systematic reviews" ] 2 => array:2 [ "identificador" => "sec0030" "titulo" => "Eligibility criteria" ] 3 => array:2 [ "identificador" => "sec0035" "titulo" => "Study selection" ] ] ] 7 => array:3 [ "identificador" => "sec0040" "titulo" => "Results" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0045" "titulo" => "Qualitative synthesis. Description of studies" ] 1 => array:2 [ "identificador" => "sec0050" "titulo" => "Part 1" ] 2 => array:2 [ "identificador" => "sec0055" "titulo" => "Part 2" ] 3 => array:2 [ "identificador" => "sec0060" "titulo" => "Expert panel consensus" ] ] ] 8 => array:2 [ "identificador" => "sec0065" "titulo" => "Discussion" ] 9 => array:2 [ "identificador" => "sec0070" "titulo" => "Conclusions" ] 10 => array:2 [ "identificador" => "sec0075" "titulo" => "Authors’ contribution" ] 11 => array:2 [ "identificador" => "sec0080" "titulo" => "Financial support" ] 12 => array:2 [ "identificador" => "sec0085" "titulo" => "Conflict of interest" ] 13 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2022-08-02" "fechaAceptado" => "2022-10-20" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1638535" "palabras" => array:5 [ 0 => "Glucocorticoids" 1 => "Osteoporosis" 2 => "Treatment" 3 => "Bone mineral density" 4 => "Thresholds" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1638536" "palabras" => array:5 [ 0 => "Glucocorticoides" 1 => "Osteoporosis" 2 => "Tratamiento" 3 => "Densidad mineral ósea" 4 => "Umbrales" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "Introduction and aimT-score bone mineral density (BMD) thresholds may influence guidance for treatment in patients under glucocorticoid (GC) therapy. Different BMD thresholds have been described but there is no international consensus. The aim of this study was to find a threshold to help in treatment decision-making in the population under GC therapy. MethodsA working group representing three scientific societies from Argentina was convened. The first team was formed by specialists with expertise in glucocorticoid-induced osteoporosis (GIO) who voted according to summary of evidence. The second team was constituted by a methodology group who coordinated and supervised each stage. We conducted two systematic reviews to synthesize the evidence. The first included trials of drugs used in GIO to analyze the BMD cut-off used as inclusion criteria. In the second, we analyzed the evidence regarding the densitometric thresholds to discriminate between fractured and non-fractured patients under GC treatment. ResultsIn the first review, 31 articles were included for qualitative synthesis and more than 90% of the trials included patients regardless of their densitometric T-score or range of osteopenia. In the second review, 4 articles were included and more than 80% of the T-scores were in the range −1.6 to −2.0. The summary of findings was analyzed and put to a vote. ConclusionsWith more than 80% agreement of the voting expert panel, a T-score≤−1.7 was considered the most appropriate for treatment in postmenopausal women and men over 50 years of age under GC therapy. This study could help in treatment decision-making in patients under GC therapy without fractures but other fracture risk factors should certainly be considered." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction and aim" ] 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" => "Introducción y objetivoLos umbrales del T-score de densidad mineral ósea (DMO) podrían influir en el tratamiento de pacientes bajo terapia con glucocorticoides (GC). Se han descrito diferentes umbrales, pero no existe un consenso internacional. El objetivo de este trabajo fue encontrar un umbral que ayude en la decisión terapéutica en la población bajo tratamiento con GC. MétodosSe convocó un grupo de trabajo en representación de tres sociedades científicas de Argentina. El primer equipo estuvo formado por especialistas con experiencia en osteoporosis inducida por glucocorticoides (OIG), quienes estuvieron a cargo de la votación basada en la evidencia. El segundo equipo estuvo a cargo de la metodología coordinando y supervisando cada etapa. Realizamos dos revisiones sistemáticas: la primera incluyó ensayos de fármacos utilizados en OIG para analizar el T-score considerado como criterio de inclusión. En la segunda, analizamos la evidencia sobre umbrales densitométricos para la discriminación de pacientes fracturados y no fracturados bajo tratamiento con GC. ResultadosEn la primera revisión se incluyeron 31 artículos donde se halló que más de 90% de los ensayos incluyeron pacientes independientemente del T-score o en el rango de osteopenia. En la segunda revisión se incluyeron cuatro artículos donde observamos que más de 80% de los valores de T-score se encontraban entre -1,6 y -2,0. ConclusionesCon un acuerdo superior a 80% del panel de expertos, un T-score ≤ -1,7 se consideró el más adecuado para el tratamiento en mujeres posmenopáusicas y hombres mayores de 50 años bajo tratamiento con GC. Este estudio podría ayudar en la decisión terapéutica en pacientes bajo tratamiento con GC sin fracturas, pero ciertamente deberían considerarse otros factores de riesgos de fracturas complementarios." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción y objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] ] "apendice" => array:1 [ 0 => array:1 [ "seccion" => array:1 [ 0 => array:4 [ "apendice" => "The following are the supplementary data to this article:<elsevierMultimedia ident="upi0005"></elsevierMultimedia><elsevierMultimedia ident="upi0010"></elsevierMultimedia><elsevierMultimedia ident="upi0015"></elsevierMultimedia>" "etiqueta" => "Appendix A" "titulo" => "Supplementary data" "identificador" => "sec0095" ] ] ] ] "multimedia" => array:6 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 4168 "Ancho" => 1697 "Tamanyo" => 434551 ] ] "descripcion" => array:1 [ "en" => "Flowcharts of both systematic review." ] ] 1 => array:8 [ "identificador" => "tbl0005" "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" => "Abbreviations: BMD: bone mineral density; GIO: glucocorticoid-induced osteoporosis; LS: lumbar spine; TH: total hip; YAM: young adult mean." "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">Densitometric inclusion criteria \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">n \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">% \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">Regardless of their baseline 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">17<a class="elsevierStyleCrossRefs" href="#bib0325">14,16–19,21–25,28–30,34–36</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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">53.1 \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">BMD T-score at the lumbar spine (LS) and total hip (TH): either ≤−2.0, or ≤−1.0 in addition to at least one fragility fracture during treatment with GC. \t\t\t\t\t\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<a class="elsevierStyleCrossRefs" href="#bib0445">38–42</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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15.6 \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">GIO according to Japanese Society for Bone and Mineral Research criteria (2004): T-score −1.7; 80% YAM. \t\t\t\t\t\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<a class="elsevierStyleCrossRefs" href="#bib0330">15,26,37</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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9.4 \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">BMD T-score at the LS or TH: ≤−2.5. \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">4<a class="elsevierStyleCrossRefs" href="#bib0355">20,27,33,43</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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12.5 \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">BMD T-score at the LS: ≥−2.0. \t\t\t\t\t\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<a class="elsevierStyleCrossRef" href="#bib0410">31</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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3.1 \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">BMD T-score at the LS: <−1.0 and ≥−2.5. \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">1<a class="elsevierStyleCrossRef" href="#bib0415">32</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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3.1 \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">BMD T-score at the LS or TH: <−1.0. \t\t\t\t\t\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<a class="elsevierStyleCrossRef" href="#bib0475">44</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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3.1 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3165778.png" ] ] ] ] "descripcion" => array:1 [ "en" => "T-score as densitometric inclusion criteria in trials about GIO." ] ] 2 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "Abbreviations: BMD: bone mineral density; GIO: glucocorticoid-induced osteoporosis; RA: rheumatoid arthritis; SLE: systemic lupus erythematosus." "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">Description \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">Population/site \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">T-score \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 " rowspan="6" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">van Staa, et al.<a class="elsevierStyleCrossRef" href="#bib0480">45</a> analyzed the BMD threshold for vertebral fracture in postmenopausal women taking GC versus placebo from 2 randomized clinical trials (prevention and treatment trials of risedronate).Total: 111 postmenopausal women (risedronate group), 56 (placebo group).Age: 59.6±1.0 (risedronate group), 57.1±1.3 (placebo group).Underlying diseases: rheumatic, pulmonary and skin disorders.</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">Control patients \t\t\t\t\t\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">Lumbar spine \t\t\t\t\t\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">−2.6 \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">Femoral neck \t\t\t\t\t\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">−2.6 \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">GC treated patients \t\t\t\t\t\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">Lumbar spine \t\t\t\t\t\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></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">Femoral neck \t\t\t\t\t\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">−1.9 \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 " rowspan="12" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Nawata H, et al.<a class="elsevierStyleCrossRef" href="#bib0485">46</a> studied the BMD T-score cut-off which discriminates among fractured and non-fractured patients.Total: 692 patients (627 women and 65 men).Underlying diseases: rheumatoid arthritis (RA, n=319), systemic lupus erythematosus (SLE, n=162), progressive systemic sclerosis (n=27), mixed connective tissue disease (n=26), polymyositis/dermatomyositis (n=20), polymyalgia rheumatica (n=16), nephropaty (n=12), and 110 with other diseases.</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">In all population \t\t\t\t\t\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">Primary 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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−2.60 \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">Osteopenia \t\t\t\t\t\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">−1.70 \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">GC treated patients: All population \t\t\t\t\t\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">−1.97 \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">GC treated patients: RA population \t\t\t\t\t\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">−2.24 \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">GC treated patients: SLE population \t\t\t\t\t\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">−1.60 \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">GC treated patients: Non-RA population \t\t\t\t\t\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">−1.40 \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">According to GC doses \t\t\t\t\t\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">≥5mg/day \t\t\t\t\t\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">−1.90 \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">≥7.5mg/day \t\t\t\t\t\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">−1.67 \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">≥10mg/day \t\t\t\t\t\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">−1.52 \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">RA population (≥7.5mg/day) \t\t\t\t\t\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">−2.12 \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 " rowspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Kumagai S, et al.<a class="elsevierStyleCrossRef" href="#bib0490">47</a> is q cross-sectional study in women who had received at least 0.5mg/kg of oral GC for more than 1 month.Total: 160 Japanese womenAge: 16–85 yearsUnderlying disease: autoimmune diseases.</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">Premenopausal women \t\t\t\t\t\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></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">Postmenopausal women \t\t\t\t\t\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">−2.1 \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 " rowspan="8" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Kaji et al.<a class="elsevierStyleCrossRef" href="#bib0495">48</a> studied the relationship between the presence or absence of vertebral fractures and BMD in 136 females Japanese patients treated with GC. They analyzed the cut-off values on BMD for the incidence of vertebral fractures in those patients compared with controls.Underlying disease: autoimmune disease (n=102), neurological disease (n=15), dermatological disease (n=6), respiratory disease (n=5), inflammatory bowel disease (n=5), haematological disease (n=5).</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">Control patients \t\t\t\t\t\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">L2–L4 \t\t\t\t\t\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">−2.36 \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">Femoral neck \t\t\t\t\t\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">−1.74 \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">Radius (1/3) \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">−2.12 \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">GC treated patients \t\t\t\t\t\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">L2–L4 \t\t\t\t\t\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">−1.88 \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">Femoral neck \t\t\t\t\t\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">−1.67 \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">Radius (1/3) \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">−1.55 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3165779.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Analysis of the BMD T-score threshold for fractured and non-fractured discrimination in patients under GC therapy." ] ] 3 => array:5 [ "identificador" => "upi0005" "tipo" => "MULTIMEDIAECOMPONENTE" "mostrarFloat" => false "mostrarDisplay" => true "Ecomponente" => array:2 [ "fichero" => "mmc1.pdf" "ficheroTamanyo" => 203609 ] ] 4 => array:5 [ "identificador" => "upi0010" "tipo" => "MULTIMEDIAECOMPONENTE" "mostrarFloat" => false "mostrarDisplay" => true "Ecomponente" => array:2 [ "fichero" => "mmc2.pdf" "ficheroTamanyo" => 180337 ] ] 5 => array:5 [ "identificador" => "upi0015" "tipo" => "MULTIMEDIAECOMPONENTE" "mostrarFloat" => false "mostrarDisplay" => true "Ecomponente" => array:2 [ "fichero" => "mmc3.pdf" "ficheroTamanyo" => 215528 ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:51 [ 0 => array:3 [ "identificador" => "bib0260" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Predictive value of BMD for hip and other fractures" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "O. 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Original article

Threshold based on bone mineral density for therapeutic decision-making in postmenopausal women and men over 50 years old under glucocorticoid therapy

Umbral densitométrico de densidad mineral ósea para considerar tratamiento en pacientes mujeres posmenopáusicas y hombres mayores de 50 años en tratamiento con glucocorticoids

María Lorena Brancea,b,c,

Corresponding author

lorenabrance@gmail.com

Corresponding author.

, María Silvia Larroudéd, Luis Fernando Sommae, Evangelina Giacoiaf, María Diehlg, Ana María Galichg, Luis Agustín Ramirez Stiebenh, María Cielo Maheri, María De La Vegaj, Ariana Ringera,k, Lucas R. Brunb,c

a Reumatología y Enfermedades Óseas, Rosario, Argentina

b Bone Biology Laboratory, School of Medicine, Rosario National University, Argentina

c National Council of Scientific and Technical Research (CONICET), Argentina

d Centro Rossi, Buenos Aires, Argentina

e Consultorio de Reumatologia y Osteoporosis, Lujan, Argentina

f Hospital Nacional Prof. A. Posadas, Buenos Aires, Argentina

g Hospital Italiano de Buenos Aires, Buenos Aires, Argentina

h Hospital Privado de Rosario (Grupo Gamma), Rosario, Argentina

i Instituto de Rehabilitación Psicofísica (IREP), Buenos Aires, Argentina

j Ceim Investigaciones Médicas, Buenos Aires, Argentina

k Hospital Provincial del Centenario, Rosario, Argentina

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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Bone mineral density &#40;BMD&#41; measured by dual X-ray absorptiometry &#40;DXA&#41; is the current gold standard reference for the diagnosis of osteoporosis&#46; Since BMD is one of the strongest predictors of fracture risk&#44; many agencies worldwide have adopted BMD-based criteria as intervention thresholds&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">1</span></a> According to existing guidelines for postmenopausal women&#44; a <span class="elsevierStyleItalic">T</span>-score of &#8722;2&#46;5 SD or lower is recommended to offer treatment in those patients without fragility fractures&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">2</span></a> The <span class="elsevierStyleItalic">T</span>-score BMD thresholds might influence current guidance for treatment in patients under glucocorticoid &#40;GC&#41; therapy&#46; Different BMD thresholds were described throughout the time&#46;<a class="elsevierStyleCrossRefs" href="#bib0270"><span class="elsevierStyleSup">3&#8211;9</span></a> Several differences exist between the 2001 and 2010 American College of Rheumatology &#40;ACR&#41; glucocorticoid-induced osteoporosis &#40;GIO&#41; guidelines&#46; In 2001&#44; the ACR guideline recommended treatment for GIO in any patient with a <span class="elsevierStyleItalic">T</span>-score below &#8722;1&#46;0&#46; On the other hand&#44; in 2010 the treatment was suggested considering the low&#44; moderate&#44; or high-risk of fracture&#46; The ASBMR-PPC &#40;American Society for Bone and Mineral Research-Professional Practice Committee&#41; also stratified postmenopausal women and men<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>50 years into low&#44; medium&#44; and high risk of fracture according to FRAX score&#46; For patients who had low risk but have an indication for prednisone &#62;7&#46;5<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#44; the recommendation is to indicate treatment but for those with lower GC doses&#44; the suggestion is to monitor the patient with BMD&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">6</span></a> In 2012&#44; the IOF-ECTS GIO Guidelines Working Group defined a BMD <span class="elsevierStyleItalic">T</span>-score lower than &#8722;1&#46;5 as one of the indications for bone-protective therapy in postmenopausal women and men &#8805;50 years under GC therapy&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">7</span></a> The Japanese guidelines also consider it as a cut-off value of BMD in around 80&#37; of the young adult population&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">10</span></a> The ACR guideline 2017 recommended initial pharmacologic treatment in adults<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>40 years of age who are at moderate-to-high risk of fracture considering high-risk to those with <span class="elsevierStyleItalic">T</span>-score<span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>&#8722;2&#46;5&#44; by FRAX GC-adjusted or with a prior fragility fracture&#46; Recently&#44; the 2020 GIO Brazilian guidelines recommended a <span class="elsevierStyleItalic">T</span>-score<span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>&#8722;1&#46;89 for treatment in men&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">8</span></a> Consequently&#44; there is no international consensus regarding the BMD cut-off for diagnosis and treatment in GIO&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">Therefore&#44; in the context of the development of Argentine guidelines for prevention and treatment of GIO&#44; a working group on behalf of three scientific societies from Argentina&#58; AAOMM &#40;<span class="elsevierStyleItalic">Asociaci&#243;n Argentina de Osteolog&#237;a y Metabolismo Mineral</span> &#8211; Argentine Association of Osteology and Mineral Metabolism&#41;&#44; SAO &#40;<span class="elsevierStyleItalic">Sociedad Argentina de Osteoporosis</span> &#8211; Argentine Osteoporosis Society&#41; and SAR &#40;<span class="elsevierStyleItalic">Sociedad Argentina de Reumatolog&#237;a</span> &#8211; Argentine Society of Rheumatology&#41; was convened to identify areas of consensus among a panel of experts&#44; with the aim of discussing the available data for the threshold based on BMD for therapeutic decision-making in postmenopausal and men<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>50 years under GC therapy&#46; In the absence of a consensus about a cut-off for the diagnosis of GIO&#44; there is a risk of not identifying those patients who&#44; under GC therapy&#44; are at risk of fragility fracture&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Objective</span><p id="par0015" class="elsevierStylePara elsevierViewall">The overall aim of this study was to find a threshold according to the reported evidence to be able to help in the treatment decision in the population under GC therapy&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Methods</span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Development teams</span><p id="par0020" class="elsevierStylePara elsevierViewall">This work involved a working group on behalf of three scientific societies from Argentina&#58; AAOMM&#44; SAO and SAR&#46; An equal number of participants was selected by each society according to its expertise&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">The first team was formed by specialists &#40;rheumatologists&#44; endocrinologists&#44; internists&#44; physiatrists&#41; with expertise and clinical experience in treating GIO and bone diseases&#46; The second team was constituted by a methodology group who coordinated and supervised each stage of the work and conducted the literature search and data abstraction&#44; rated the quality of evidence&#44; analyzed the data&#44; and created the tables of summary of findings&#46; In the framework of two virtual meetings&#44; the methodology and summary of findings of the two systematic reviews were shown to the voting expert panel who discuss about the threshold based on BMD for therapeutic decision-making in postmenopausal and men<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>50 years under GC therapy&#46; The voting expert panel voted both diagnostic questions requiring 70&#37; agreement among the voting members&#46; Diagnostic questions&#58; 1&#46; What was the densitometric threshold used as inclusion criteria in the population treated with GC in the trials that studied drugs for GIO&#63; 2&#46; What would be the best densitometric threshold that discriminates among fractures and non fractures in patient under GC treatment&#63;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Systematic reviews</span><p id="par0030" class="elsevierStylePara elsevierViewall">Two systematic reviews were performed &#40;<a class="elsevierStyleCrossRef" href="#sec0095">Appendix 1</a>&#41;&#46; In the first systematic review the literature was searched for key terms until October 2020&#44; using the databases of MEDLINE &#40;National Library of Medicine&#41; &#40;<a href="https://pubmed.ncbi.nlm.nih.gov/">https&#58;&#47;&#47;pubmed&#46;ncbi&#46;nlm&#46;nih&#46;gov&#47;</a>&#41;&#44; Cochrane Library &#40;<a href="https://www.cochranelibrary.com/">https&#58;&#47;&#47;www&#46;cochranelibrary&#46;com&#47;</a>&#41; and LILACS &#40;<a href="https://lilacs.bvsalud.org/es/">https&#58;&#47;&#47;lilacs&#46;bvsalud&#46;org&#47;es&#47;</a>&#41;&#44; and grey literature in the last 5 years&#46; This review was performed in the context of the development of Argentine guidelines for prevention and treatment of GIO under PICO structure&#46; In this first review&#44; the focus was to evaluate the <span class="elsevierStyleItalic">T</span>-score cut-off used in the trials that evaluated pharmacological intervention in GIO&#46; In the second systematic review&#44; the literature was searched for key terms until February 2022 and aimed to search for evidence about the BMD <span class="elsevierStyleItalic">T</span>-score threshold that discriminates between fractured and non-fractured populations&#46; An expert panel reviewed the included studies selected in both systematic reviews&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Eligibility criteria</span><p id="par0035" class="elsevierStylePara elsevierViewall">We included randomized controlled trials&#44; non-randomized trials&#44; post hoc analysis and pooled analysis in postmenopausal women and men older than 50 years old&#44; in which the <span class="elsevierStyleItalic">T</span>-score BMD baseline was reported studying a pharmacological treatment in patients under GC therapy &#40;&#8805;5<span class="elsevierStyleHsp" style=""></span>mg&#47;day prednisolone or equivalent&#41; regardless of GC administration time&#46; <span class="elsevierStyleItalic">T</span>-scores BMD in the lumbar spine &#40;LS&#41; or total hip &#40;TH&#41;&#44; thresholds <span class="elsevierStyleItalic">T</span>-scores BMD values were considered as outcomes&#46; Only articles in English&#44; Portuguese and Spanish were included&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Case reports&#44; reviews&#44; letters to the editor&#44; animal studies&#44; editorials&#44; commentaries&#44; other languages than the described previously&#44; and if identical data were re-analyzed were considered as exclusion criteria&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Study selection</span><p id="par0045" class="elsevierStylePara elsevierViewall">Rayyan software &#40;<a href="https://rayyan-prod.qcri.org/welcome">https&#58;&#47;&#47;rayyan-prod&#46;qcri&#46;org&#47;welcome</a>&#41; was used to screen the literature search results&#46; Two independent reviewers performed the title and abstract screening and then underwent full-text screening&#46; A third reviewer was included in case of conflicts&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">The data extraction and processing were obtained by two authors independently using a standardized data extraction&#58; authors&#44; study design&#44; participants&#44; age of participants&#44; time and dose of GC&#44; diagnostic used for osteoporosis&#44; baseline <span class="elsevierStyleItalic">T</span>-score value in each group&#44; intervention&#44; comparator&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">The quality assessment and publication bias of randomized controlled trials were judged using the Cochrane risk of bias tool &#40;<a href="http://handbook.cochrane.org/">http&#58;&#47;&#47;handbook&#46;cochrane&#46;org&#47;</a>&#41;&#46; For non-randomized controlled trials&#44; the assessment was performed using the Newcastle&#8211;Ottawa scale &#40;NOS&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">11</span></a> For cross-sectional studies&#44; we used a modified version of NOS and studies that received at least seven stars &#40;maximum of ten&#41; were classified as good quality&#46; The PRISMA-P guideline was used to prepare this systematic review&#46;<a class="elsevierStyleCrossRefs" href="#bib0315"><span class="elsevierStyleSup">12&#44;13</span></a></p></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Results</span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Qualitative synthesis&#46; Description of studies</span><p id="par0060" class="elsevierStylePara elsevierViewall">The studies were divided into two parts according to each search&#58; Part 1 included the trials of drugs used in GIO&#44; while Part 2 included BMD thresholds for fractured and non-fractured patients&#8217; discrimination under GC therapy&#46; The flowcharts of both systematic reviews are shown in <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#44; and the quality assessment of the studies is in <a class="elsevierStyleCrossRef" href="#sec0095">Appendix 2</a>&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Part 1</span><p id="par0065" class="elsevierStylePara elsevierViewall">In this first revision&#44; a total of 1214 selected articles were found&#46; A total of 31 articles were included for qualitative synthesis and we stratify the trials according to the densitometric <span class="elsevierStyleItalic">T</span>-score used as inclusion criteria in each trial&#46;<a class="elsevierStyleCrossRefs" href="#bib0325"><span class="elsevierStyleSup">14&#8211;44</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">The summary of the studies characteristics is shown in <a class="elsevierStyleCrossRef" href="#sec0095">Appendix 3</a>&#46; The 93&#46;7&#37; of the trials included patients regardless of the densitometric <span class="elsevierStyleItalic">T</span>-score or in the range of osteopenia &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Part 2</span><p id="par0075" class="elsevierStylePara elsevierViewall">In this second revision a total of 54 selected articles were found and 4 articles were included&#46;<a class="elsevierStyleCrossRefs" href="#bib0480"><span class="elsevierStyleSup">45&#8211;48</span></a> More than 80&#37; of the <span class="elsevierStyleItalic">T</span>-scores were between the &#8722;1&#46;6 and &#8722;2&#46;0 range &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Expert panel consensus</span><p id="par0080" class="elsevierStylePara elsevierViewall">After analyzing the evidence from both systematic reviews&#44; the expert panel discussed in meetings in the framework of a working group with experts in bone diseases&#46; The expert panel voted on the threshold of the BMD <span class="elsevierStyleItalic">T</span>-score that best identifies fractured from the non-fractured population&#46; Taking into account that more than 90&#37; of the trials about GIO included patients regardless of the densitometric <span class="elsevierStyleItalic">T</span>-score or in the range of osteopenia&#44; and more than 80&#37; of the <span class="elsevierStyleItalic">T</span>-scores that discriminates between fractured and non-fractured patients are within &#8722;1&#46;6 and &#8722;2&#46;0&#44; the voting was performed among this range&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">With an agreement over 80&#37; of the voting expert panel&#44; a <span class="elsevierStyleItalic">T</span>-score<span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>&#8722;1&#46;7 was considered the most appropriate for treatment in postmenopausal women and men older than 50 years under GC therapy&#46;</p></span></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Discussion</span><p id="par0090" class="elsevierStylePara elsevierViewall">The <span class="elsevierStyleItalic">T</span>-score BMD thresholds might influence current guidance for treatment in patients under GC treatment&#46; Several published guidelines for GIO management demonstrate large differences in the thresholds in patients under GC treatment as were previously detailed&#46; In GIO there is no international consensus regarding the most appropriate BMD threshold for treatment&#46; Therefore&#44; we considered conducting this systematic review in the context of the development of Argentine guidelines for prevention and treatment of glucocorticoid-induced osteoporosis by 3 scientific societies from Argentina to determine the most appropriate BMD <span class="elsevierStyleItalic">T</span>-score threshold to help in the GIO treatment decision&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">As far as we know&#44; the thresholds are noy ideal from every perspective and there is no <span class="elsevierStyleItalic">T</span>-score BMD threshold gold standard established by international consensus in GIO&#46; At the same time&#44; the fracture incidence differs markedly in different regions of the world&#44; accordingly to ethnicity among other variables&#46;<a class="elsevierStyleCrossRef" href="#bib0500"><span class="elsevierStyleSup">49</span></a> Despite it being suggested that each country should determine their own intervention thresholds&#44; based on fracture incidence&#44; availability of resources&#44; and economic considerations&#44; these data are not always available&#46; Therefore&#44; the fracture risk assessment tool &#40;FRAX&#41; was developed to estimate the 10-year probability of fractures&#46;<a class="elsevierStyleCrossRef" href="#bib0505"><span class="elsevierStyleSup">50</span></a> Dawson-Hughes et al&#46; identified cost-effective intervention thresholds based on 10-year absolute hip fracture risk&#46; With BMD in osteopenia levels &#40;<span class="elsevierStyleItalic">T</span>-score &#8722;2&#46;0&#41; plus a clinical risk factor&#44; the absolute fracture probability estimate meets or exceeds the 3&#37; cost-effectiveness threshold in all instances&#46;<a class="elsevierStyleCrossRef" href="#bib0510"><span class="elsevierStyleSup">51</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">Previous studies have evaluated BMD thresholds for discrimination of fractured and non-fractured patients under GC therapy&#46;<a class="elsevierStyleCrossRefs" href="#bib0480"><span class="elsevierStyleSup">45&#8211;48</span></a> Kaji et al&#46; analyzed the threshold of BDM for vertebral fracture in Japanese female patients with GIO&#46;<a class="elsevierStyleCrossRef" href="#bib0495"><span class="elsevierStyleSup">48</span></a> The cut-off values of BMD which discriminates patients with vertebral fractures from those without vertebral fractures were higher in patients with GC treatment&#46; They found a cut-off for vertebral fracture of &#8722;1&#46;88 in lumbar spine BMD &#40;sensitivity and specificity 61&#46;5&#37;&#41; and &#8722;1&#46;67 in femoral neck BMD &#40;sensitivity and specificity 70&#46;9&#37;&#41;&#46; Nawata et al&#46;&#44; in the context of the GIO Japanese guidelines&#44; described the results of a longitudinal study in which the BMD <span class="elsevierStyleItalic">T</span>-score cut-off was discriminated between fractures and non-fractures&#46;<a class="elsevierStyleCrossRef" href="#bib0485"><span class="elsevierStyleSup">46</span></a> Considering the whole GC treated group &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>692&#41;&#44; the cut-off found was a <span class="elsevierStyleItalic">T</span>-score of &#8722;1&#46;97&#46; Van Staa TP et al&#46;&#44; after analyzing data from 2 large&#44; prospective&#44; randomized controlled trials &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>306&#41; showed that the daily GC dose&#44; and not the cumulative dose&#44; is a strong predictor of the risk of vertebral fracture in postmenopausal women under GC therapy&#44; at similar baseline levels of BMD&#46; They described a <span class="elsevierStyleItalic">T</span>-score threshold of &#8722;1&#46;8 for the lumbar spine and &#8722;1&#46;9 for femoral neck BMD&#46;<a class="elsevierStyleCrossRef" href="#bib0480"><span class="elsevierStyleSup">45</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">In summary&#44; the voting expert panel selected a BMD <span class="elsevierStyleItalic">T</span>-score<span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>&#8722;1&#46;7 as the most appropriate for help in the treatment decision in postmenopausal women and men older than 50 years under GC therapy&#46; This agreement was reached after prolonged discussion and debate&#46; Lower <span class="elsevierStyleItalic">T</span>-scores were not selected because lack of evidence was considered and to avoid overtreatment even when there is not enough data on the different ethnic groups and populations&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">One of the limitations of this paper is that the analysis is based on indirect data from systematic reviews and most data come from the Japanese population&#46; However&#44; two exhaustive systematic reviews were conducted&#44; addressing the problem from two perspectives as a strength&#46; Therefore&#44; longitudinal studies according to age&#44; gender and ethnicity are needed to identify the optimal BMD threshold&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Conclusions</span><p id="par0115" class="elsevierStylePara elsevierViewall">With an agreement over 80&#37; of the voting expert panel&#44; a <span class="elsevierStyleItalic">T</span>-score<span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>&#8722;1&#46;7 was considered the most appropriate for treatment in postmenopausal women and men older than 50 years under GC therapy&#46; This study could help in the treatment decision in patients under GC therapy without fractures but certainly should consider other concepts as age&#44; sex&#44; fracture history&#44; risk fracture stratification&#44; FRAX&#44; among others&#46;</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Authors&#8217; contribution</span><p id="par0120" class="elsevierStylePara elsevierViewall">MLB&#58; study design and scope of these systematic reviews&#46; MLB&#44; MSL&#44; LFS&#44; EG&#44; MD&#44; AMG&#44; LARS&#44; MDLV&#58; voting expert panel&#46; MLB&#44; AR&#44; LARS&#44; CM&#44; LRB&#58; performed the systematic review&#46; MLB and LRB&#58; drafting of the manuscript&#46; All authors read&#44; discussed&#44; and approved the final manuscript&#46;</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Financial support</span><p id="par0125" class="elsevierStylePara elsevierViewall">None&#46;</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Conflict of interest</span><p id="par0130" class="elsevierStylePara elsevierViewall">Maria Lorena Brance received lecture fees from Amgen and Craveri and fees as an advisory board from Amgen&#46; Mar&#237;a Silvia Larroud&#233; received lecture fees from Pfizer&#44; Lilly&#44; Amgen&#44; Astrazeneca and Genzyme Sanofi&#46; Evangelina Giacoia received lecture fees and fees as an advisory board from Amgen&#46; Mar&#237;a Diehl received research support from Amgen&#46; Ana Mar&#237;a Galich received lecture fees from Raffo&#44; Amgen and Eli Lilly&#46; Luis Fernando Somma&#44; Luis Agust&#237;n Ramirez Stieben&#44; Mar&#237;a Cielo Maher&#44; Maria Celina de la Vega&#44; Ariana Ringer&#44; and Lucas R Brun reported no conflicts of interest&#46;</p></span></span>"
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            4 => "Umbrales"
          ]
        ]
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    "resumen" => array:2 [
      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction and aim</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">T</span>-score bone mineral density &#40;BMD&#41; thresholds may influence guidance for treatment in patients under glucocorticoid &#40;GC&#41; therapy&#46; Different BMD thresholds have been described but there is no international consensus&#46; The aim of this study was to find a threshold to help in treatment decision-making in the population under GC therapy&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A working group representing three scientific societies from Argentina was convened&#46; The first team was formed by specialists with expertise in glucocorticoid-induced osteoporosis &#40;GIO&#41; who voted according to summary of evidence&#46; The second team was constituted by a methodology group who coordinated and supervised each stage&#46; We conducted two systematic reviews to synthesize the evidence&#46; The first included trials of drugs used in GIO to analyze the BMD cut-off used as inclusion criteria&#46; In the second&#44; we analyzed the evidence regarding the densitometric thresholds to discriminate between fractured and non-fractured patients under GC treatment&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">In the first review&#44; 31 articles were included for qualitative synthesis and more than 90&#37; of the trials included patients regardless of their densitometric <span class="elsevierStyleItalic">T</span>-score or range of osteopenia&#46; In the second review&#44; 4 articles were included and more than 80&#37; of the <span class="elsevierStyleItalic">T</span>-scores were in the range &#8722;1&#46;6 to &#8722;2&#46;0&#46; The summary of findings was analyzed and put to a vote&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">With more than 80&#37; agreement of the voting expert panel&#44; a <span class="elsevierStyleItalic">T</span>-score<span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>&#8722;1&#46;7 was considered the most appropriate for treatment in postmenopausal women and men over 50 years of age under GC therapy&#46; This study could help in treatment decision-making in patients under GC therapy without fractures but other fracture risk factors should certainly be considered&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Introduction and aim"
          ]
          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" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introducci&#243;n y objetivo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Los umbrales del <span class="elsevierStyleItalic">T-score</span> de densidad mineral &#243;sea &#40;DMO&#41; podr&#237;an influir en el tratamiento de pacientes bajo terapia con glucocorticoides &#40;GC&#41;&#46; Se han descrito diferentes umbrales&#44; pero no existe un consenso internacional&#46; El objetivo de este trabajo fue encontrar un umbral que ayude en la decisi&#243;n terap&#233;utica en la poblaci&#243;n bajo tratamiento con GC&#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 convoc&#243; un grupo de trabajo en representaci&#243;n de tres sociedades cient&#237;ficas de Argentina&#46; El primer equipo estuvo formado por especialistas con experiencia en osteoporosis inducida por glucocorticoides &#40;OIG&#41;&#44; quienes estuvieron a cargo de la votaci&#243;n basada en la evidencia&#46; El segundo equipo estuvo a cargo de la metodolog&#237;a coordinando y supervisando cada etapa&#46; Realizamos dos revisiones sistem&#225;ticas&#58; la primera incluy&#243; ensayos de f&#225;rmacos utilizados en OIG para analizar el <span class="elsevierStyleItalic">T-score</span> considerado como criterio de inclusi&#243;n&#46; En la segunda&#44; analizamos la evidencia sobre umbrales densitom&#233;tricos para la discriminaci&#243;n de pacientes fracturados y no fracturados bajo tratamiento con GC&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">En la primera revisi&#243;n se incluyeron 31 art&#237;culos donde se hall&#243; que m&#225;s de 90&#37; de los ensayos incluyeron pacientes independientemente del <span class="elsevierStyleItalic">T-score</span> o en el rango de osteopenia&#46; En la segunda revisi&#243;n se incluyeron cuatro art&#237;culos donde observamos que m&#225;s de 80&#37; de los valores de <span class="elsevierStyleItalic">T-score</span> se encontraban entre -1&#44;6 y -2&#44;0&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Con un acuerdo superior a 80&#37; del panel de expertos&#44; un <span class="elsevierStyleItalic">T-score</span> &#8804; -1&#44;7 se consider&#243; el m&#225;s adecuado para el tratamiento en mujeres posmenop&#225;usicas y hombres mayores de 50 a&#241;os bajo tratamiento con GC&#46; Este estudio podr&#237;a ayudar en la decisi&#243;n terap&#233;utica en pacientes bajo tratamiento con GC sin fracturas&#44; pero ciertamente deber&#237;an considerarse otros factores de riesgos de fracturas complementarios&#46;</p></span>"
        "secciones" => array:4 [
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            "identificador" => "abst0025"
            "titulo" => "Introducci&#243;n y objetivo"
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          1 => array:2 [
            "identificador" => "abst0030"
            "titulo" => "M&#233;todos"
          ]
          2 => array:2 [
            "identificador" => "abst0035"
            "titulo" => "Resultados"
          ]
          3 => array:2 [
            "identificador" => "abst0040"
            "titulo" => "Conclusiones"
          ]
        ]
      ]
    ]
    "apendice" => array:1 [
      0 => array:1 [
        "seccion" => array:1 [
          0 => array:4 [
            "apendice" => "<p id="par0140" class="elsevierStylePara elsevierViewall">The following are the supplementary data to this article&#58;<elsevierMultimedia ident="upi0005"></elsevierMultimedia><elsevierMultimedia ident="upi0010"></elsevierMultimedia><elsevierMultimedia ident="upi0015"></elsevierMultimedia></p>"
            "etiqueta" => "Appendix A"
            "titulo" => "Supplementary data"
            "identificador" => "sec0095"
          ]
        ]
      ]
    ]
    "multimedia" => array:6 [
      0 => array:7 [
        "identificador" => "fig0005"
        "etiqueta" => "Fig&#46; 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
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        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Flowcharts of both systematic review&#46;</p>"
        ]
      ]
      1 => array:8 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
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          "leyenda" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Abbreviations</span>&#58; BMD&#58; bone mineral density&#59; GIO&#58; glucocorticoid-induced osteoporosis&#59; LS&#58; lumbar spine&#59; TH&#58; total hip&#59; YAM&#58; young adult mean&#46;</p>"
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                  <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">Densitometric inclusion criteria&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
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">n</span>&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
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&#37;&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">Regardless of their baseline BMD&#46;&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">17<a class="elsevierStyleCrossRefs" href="#bib0325"><span class="elsevierStyleSup">14&#44;16&#8211;19&#44;21&#8211;25&#44;28&#8211;30&#44;34&#8211;36</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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">53&#46;1&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">BMD <span class="elsevierStyleItalic">T</span>-score at the lumbar spine &#40;LS&#41; and total hip &#40;TH&#41;&#58; either &#8804;&#8722;2&#46;0&#44; or &#8804;&#8722;1&#46;0 in addition to at least one fragility fracture during treatment with GC&#46;&nbsp;\t\t\t\t\t\t\n
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                  \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<a class="elsevierStyleCrossRefs" href="#bib0445"><span class="elsevierStyleSup">38&#8211;42</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="char" valign="\n
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                  \t\t\t\t">15&#46;6&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
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">GIO according to Japanese Society for Bone and Mineral Research criteria &#40;2004&#41;&#58; <span class="elsevierStyleItalic">T</span>-score &#8722;1&#46;7&#59; 80&#37; YAM&#46;&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<a class="elsevierStyleCrossRefs" href="#bib0330"><span class="elsevierStyleSup">15&#44;26&#44;37</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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9&#46;4&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">BMD <span class="elsevierStyleItalic">T</span>-score at the LS or TH&#58; &#8804;&#8722;2&#46;5&#46;&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<a class="elsevierStyleCrossRefs" href="#bib0355"><span class="elsevierStyleSup">20&#44;27&#44;33&#44;43</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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12&#46;5&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">BMD <span class="elsevierStyleItalic">T</span>-score at the LS&#58; &#8805;&#8722;2&#46;0&#46;&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
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                  \t\t\t\t">1<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">31</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="char" valign="\n
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                  \t\t\t\t">3&#46;1&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">BMD <span class="elsevierStyleItalic">T</span>-score at the LS&#58; &#60;&#8722;1&#46;0 and &#8805;&#8722;2&#46;5&#46;&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
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                  \t\t\t\t">1<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">32</span></a>&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">3&#46;1&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">BMD <span class="elsevierStyleItalic">T</span>-score at the LS or TH&#58; &#60;&#8722;1&#46;0&#46;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">3&#46;1&nbsp;\t\t\t\t\t\t\n
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          "leyenda" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Abbreviations</span>&#58; BMD&#58; bone mineral density&#59; GIO&#58; glucocorticoid-induced osteoporosis&#59; RA&#58; rheumatoid arthritis&#59; SLE&#58; systemic lupus erythematosus&#46;</p>"
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                0 => """
                  <table border="0" frame="\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">Description&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Population&#47;site&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"><span class="elsevierStyleItalic">T</span>-score&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
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                  \t\t\t\t  " rowspan="6" align="left" valign="\n
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                  \t\t\t\t">van Staa&#44; et al&#46;<a class="elsevierStyleCrossRef" href="#bib0480"><span class="elsevierStyleSup">45</span></a> analyzed the BMD threshold for vertebral fracture in postmenopausal women taking GC versus placebo from 2 randomized clinical trials &#40;prevention and treatment trials of risedronate&#41;&#46;Total&#58; 111 postmenopausal women &#40;risedronate group&#41;&#44; 56 &#40;placebo group&#41;&#46;Age&#58; 59&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;0 &#40;risedronate group&#41;&#44; 57&#46;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;3 &#40;placebo group&#41;&#46;Underlying diseases&#58; rheumatic&#44; pulmonary and skin disorders&#46;</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"><span class="elsevierStyleBold">Control patients</span>&nbsp;\t\t\t\t\t\t\n
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                  \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
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                  \t\t\t\t">Lumbar spine&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">&#8722;2&#46;6&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">Femoral neck&nbsp;\t\t\t\t\t\t\n
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                  \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">&#8722;2&#46;6&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="elsevierStyleBold">GC treated patients</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="" 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">Lumbar spine&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">&#8722;1&#46;8&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">Femoral neck&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">&#8722;1&#46;9&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  " rowspan="12" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Nawata H&#44; et al&#46;<a class="elsevierStyleCrossRef" href="#bib0485"><span class="elsevierStyleSup">46</span></a> studied the BMD <span class="elsevierStyleItalic">T</span>-score cut-off which discriminates among fractured and non-fractured patients&#46;Total&#58; 692 patients &#40;627 women and 65 men&#41;&#46;Underlying diseases&#58; rheumatoid arthritis &#40;RA&#44; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>319&#41;&#44; systemic lupus erythematosus &#40;SLE&#44; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>162&#41;&#44; progressive systemic sclerosis &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>27&#41;&#44; mixed connective tissue disease &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>26&#41;&#44; polymyositis&#47;dermatomyositis &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>20&#41;&#44; polymyalgia rheumatica &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>16&#41;&#44; nephropaty &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>12&#41;&#44; and 110 with other diseases&#46;</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="elsevierStyleBold">In all population</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="" 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">Primary osteoporosis&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">&#8722;2&#46;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">Osteopenia&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">&#8722;1&#46;70&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">GC treated patients&#58; All population&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">&#8722;1&#46;97&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">GC treated patients&#58; RA population&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">&#8722;2&#46;24&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">GC treated patients&#58; SLE population&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">&#8722;1&#46;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">GC treated patients&#58; Non-RA population&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">&#8722;1&#46;40&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="elsevierStyleBold">According to GC doses</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="" 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">&#8805;5<span class="elsevierStyleHsp" style=""></span>mg&#47;day&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">&#8722;1&#46;90&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">&#8805;7&#46;5<span class="elsevierStyleHsp" style=""></span>mg&#47;day&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">&#8722;1&#46;67&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">&#8805;10<span class="elsevierStyleHsp" style=""></span>mg&#47;day&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">&#8722;1&#46;52&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">RA population &#40;&#8805;7&#46;5<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#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">&#8722;2&#46;12&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  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Kumagai S&#44; et al&#46;<a class="elsevierStyleCrossRef" href="#bib0490"><span class="elsevierStyleSup">47</span></a> is q cross-sectional study in women who had received at least 0&#46;5<span class="elsevierStyleHsp" style=""></span>mg&#47;kg of oral GC for more than 1 month&#46;Total&#58; 160 Japanese womenAge&#58; 16&#8211;85 yearsUnderlying disease&#58; autoimmune diseases&#46;</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">Premenopausal women&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">&#8722;1&#46;7&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">Postmenopausal women&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">&#8722;2&#46;1&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  " rowspan="8" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Kaji et al&#46;<a class="elsevierStyleCrossRef" href="#bib0495"><span class="elsevierStyleSup">48</span></a> studied the relationship between the presence or absence of vertebral fractures and BMD in 136 females Japanese patients treated with GC&#46; They analyzed the cut-off values on BMD for the incidence of vertebral fractures in those patients compared with controls&#46;Underlying disease&#58; autoimmune disease &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>102&#41;&#44; neurological disease &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>15&#41;&#44; dermatological disease &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>6&#41;&#44; respiratory disease &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>5&#41;&#44; inflammatory bowel disease &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>5&#41;&#44; haematological disease &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>5&#41;&#46;</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="elsevierStyleBold">Control patients</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="" 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">L2&#8211;L4&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">&#8722;2&#46;36&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">Femoral neck&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">&#8722;1&#46;74&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">Radius &#40;1&#47;3&#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">&#8722;2&#46;12&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="elsevierStyleBold">GC treated patients</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="" 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">L2&#8211;L4&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">&#8722;1&#46;88&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">Femoral neck&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">&#8722;1&#46;67&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">Radius &#40;1&#47;3&#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">&#8722;1&#46;55&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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Article information

ISSN: 21735743
Original language: English

DOI:10.1016/j.reumae.2022.10.002

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