Original Article
Osteonecrosis in Systemic Lupus Erythematosus
Osteonecrosis en lupus eritematoso sistémico
Romina Patricia Gontero, María Eugenia Bedoya, Emilio Benavente, Susana Graciela Roverano, Sergio Oscar Paira
Corresponding author
Sección Reumatología, Hospital José María Cullen, Santa Fe, Argentina
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Incidence of ON in SLE varies from 2.1% to 52%.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1–19</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Multiple factors have been associated with ON in SLE, including: Cushing's phenotype,<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1–7</span></a> Raynaud's phenomenon,<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4,5,8</span></a> vasculitis,<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4,6</span></a> neurological involvement,<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,8</span></a> disease activity,<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9,10</span></a> arthritis<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> cytotoxic treatment,<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,3</span></a> superficial thrombophlebitis<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> hematuria and proteinuria<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> and antiphospholipid antibodies,<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,6</span></a> among others. There is consensus among most authors regarding the relationship of ON with steroid treatment, but there is controversy whether this relationship depends on the cumulative dose, duration of treatment or the use of large monthly or bimonthly doses. The objectives of this study were to determine the proportion and distribution of bone necrosis in this population and to identify factors associated with its development.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Materials and Methods</span><p id="par0015" class="elsevierStylePara elsevierViewall">158 files of patients diagnosed with SLE who were treated at the JM Cullen Hospital in Santa Fe between 1989 and 2012 were retrospectively reviewed. They all met at least 4 classification criteria for SLE (ACR 1982).</p><p id="par0020" class="elsevierStylePara elsevierViewall">Patients considered for inclusion into the study were those in whom the diagnosis of ON was clinically suspected and confirmed through X-rays (Rx), computed tomography (CT), magnetic resonance imaging (MRI) and/or scintigraphy. ON was staged using the Ficat and Arlet<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> classification at baseline and at the last valuation of the joint: stage <span class="elsevierStyleSmallCaps">I:</span> normal radiograph with positive MRI, CT scan or pathology; stage <span class="elsevierStyleSmallCaps">II</span>: cystic or sclerotic changes in the X-ray with no signs of collapse; stage <span class="elsevierStyleSmallCaps">iii:</span> collapse of the affected bone, and stage <span class="elsevierStyleSmallCaps">iv:</span> both sides of the joint showing degenerative changes.</p><p id="par0025" class="elsevierStylePara elsevierViewall">Both groups of patients with SLE (with and without ON), were compared for: demographic data, clinical manifestations, comorbidities, antibody profile, accumulated damage by Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) damage index at first, second, fifth and tenth year of SLE progression, excluding the score for ON; activity of Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and exposure to immunosuppressive and antimalarial drugs prior to diagnosis of ON. Total cumulative dose of steroids was also reviewed and expressed as prednisone equivalents up until the diagnosis of ON or until the last control in patients who did present this complication, the duration of steroid therapy and the average daily dose that each patient received since the onset until treatment with corticosteroids ended. Methylprednisolone pulses were defined as the administration of 1000<span class="elsevierStyleHsp" style=""></span>mg or more of prednisone equivalents.</p><p id="par0030" class="elsevierStylePara elsevierViewall">The antibody profile included: antinuclear antibody (Hep 2 epithelial cells), anti-native DNA antibodies by indirect immunofluorescence on Crithidia luciliae, anti-extractable core antigen (anti-Ro, anti-La, anti-Sm and anti-RNP), anticardiolipin (IgG, IgM) and lupus anticoagulant.</p><p id="par0035" class="elsevierStylePara elsevierViewall">The study was approved by the Ethics Committee of the Hospital. It did not require informed consent because of the anonymous nature of the study.</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Statistical Analysis</span><p id="par0040" class="elsevierStylePara elsevierViewall">The Mann–Whitney test was used for comparison of means and proportions and for equal or independent proportions. The chi-square or Fisher's exact test was employed, as appropriate. Data were processed using SPSS 17.0, available from the Department of Mathematics FBCB-UNL. Statistical significance was set at 0.05.</p></span></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Results</span><p id="par0045" class="elsevierStylePara elsevierViewall">The total population of 158 patients with SLE was composed of 92% women, with an average age of onset of SLE of 28 years (<span class="elsevierStyleItalic">R</span>=9–62). Time on follow-up (median) was 87 months (<span class="elsevierStyleItalic">R</span>=0–497).</p><p id="par0050" class="elsevierStylePara elsevierViewall">Among the 158 patients with SLE, 15 were identified as presenting ON (9.5%), 13 women and 2 men. The median time between the onset of SLE and diagnosis of ON was 35 months (<span class="elsevierStyleItalic">R</span>=1–195), the mean age at ON diagnosis was 30 years (<span class="elsevierStyleItalic">R</span>=16–66). Only 6/15 of ON patients had SLEDAI data in the year prior to an episode of ON and 3 of them showed activity of SLE, while four were active at the time of developing ON.</p><p id="par0055" class="elsevierStylePara elsevierViewall">These 15 patients had a total of 34 affected joints: 23 were symptomatic, 9 were asymptomatic and in 2 cases the form of presentation was unknown. Twenty-two were diagnosed by MRI, 7 by X-ray and 2 using CT, with the rest diagnosed by a combination of methods (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). The most commonly affected site was the femoral head (14 patients), being bilateral in 12 cases. These were followed in frequency by the knees and shoulders in 2 patients in each case, and all of them bilaterally (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>). Thirteen patients had 2 or more joints involved. Initially, 28 joints were at a precollapse stadium and, in the last evaluation, 14 joints showed radiographic signs of collapse (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>). 8 joints were subjected to arthroplasty due to persistent pain or limitation of range of motion (<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>).</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><p id="par0060" class="elsevierStylePara elsevierViewall">When patients with SLE with and without ON were compared, differences in age at onset of disease, gender ratio, duration of lupus and average mean SLEDAI were seen. Comparing comorbidities, clinical and antibody profiles, only a statistically significant association between ON and Cushing's phenotype was found (60% vs 26.5%, <span class="elsevierStyleItalic">P</span>=.014, odds ratio 4.16<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,4–6,6–12</span></a>), as shown in <a class="elsevierStyleCrossRef" href="#tbl0025">Table 5</a>.</p><elsevierMultimedia ident="tbl0025"></elsevierMultimedia><p id="par0065" class="elsevierStylePara elsevierViewall">The mean cumulative damage at the second year was significantly higher in patients with ON (<span class="elsevierStyleItalic">P</span>=.042), as shown in <a class="elsevierStyleCrossRef" href="#tbl0030">Table 6</a>.</p><elsevierMultimedia ident="tbl0030"></elsevierMultimedia><p id="par0070" class="elsevierStylePara elsevierViewall">When compared against treatments we found no differences in exposure to cytotoxic therapy or pulse methylprednisolone, but it is worth noting that 100% of patients with ON, unlike 77% of patients without ON, had received antimalarials. With regard to steroid treatment, we found no differences in total cumulative dose (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>) or average daily dose in mg/day (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>), nor on the duration of treatment (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Discussion</span><p id="par0075" class="elsevierStylePara elsevierViewall">ON is the osteoarticular manifestation that generates the highest morbidity in patients with SLE, first described by Dubois and Cozen in 1960.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> ON prevalence in this population was 9.5% and this value is comparable with those reported in other series.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1–4,7,8,13–15,18</span></a></p><p id="par0080" class="elsevierStylePara elsevierViewall">Coinciding with what has been published, ON prevails in females, the joint most commonly affected is the hip, followed by the knee and shoulder, in most cases on a bilateral basis, and it commonly involves 2 or more joints.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1–5,7,9–18</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">Corticosteroids have been widely related in the pathogenesis of ON. The duration of treatment,<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> the total cumulative dose,<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> the mean daily dose<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,6,14</span></a> and the use of high doses or large cumulative doses of steroids at different times during the first year of the disease<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,2,5,14,15</span></a> have been reported as important factors in the development of this complication. Massardo et al.,<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> found that patients with ON had no higher cumulative doses of steroids or higher average daily dose of steroids, but the duration of treatment was shorter. This would imply that patients with ON receive large doses of corticosteroids in a short period of time. According to Mok et al.,<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> the need for high initial doses of steroids to control the disease is a risk factor, especially if patients are positive to anticardiolipin antibodies or develop Cushing's phenotype.</p><p id="par0090" class="elsevierStylePara elsevierViewall">With respect to the use of pulse methylprednisolone intravenously, Massardo et al.,<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> consider it a risk factor for ON; however, Migliaresi et al.,<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> found no increased risk in patients receiving methylprednisolone pulses. Rather, this treatment regimen seems to reduce risk.</p><p id="par0095" class="elsevierStylePara elsevierViewall">Our results, like those published by other authors show that the total cumulative dose<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,5,7,9,15–17</span></a> the average daily dose,<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,5,7,16</span></a> duration of steroid treatment<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,2,5,7</span></a> and methylprednisolone pulse therapy<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,15,18</span></a> are not associated with the development of ON. It is possible that ON reveals patients who have a special sensitivity to corticosteroids, as is shown with the relationship to Cushing's phenotype (as reported by Gladman et al.).<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">A highly significant association between prior Cushing phenotype and development of ON has been observed in this and other studies.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1–7</span></a> It is possible that increased deposition of fat in these patients at the trunk level is accompanied by an increase in the size and/or number of intramedullary lipocytes.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> Zizic et al.,<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> postulate that treatment with corticosteroids results in hypertrophy of intramedullary lipocytes, that due to the rigid nature of the bone leads to an increase in the pressure of the bone marrow. This increased pressure results in decreased blood flow and ischemia. Ischemic tissue becomes edematous, resulting in a further increase in pressure with a potentiation of ischemia due to secondary compartment syndrome. Indirect evidence supporting this pathogenesis comes from results of core decompression treatment, which provides rapid relief of symptoms and can stop the disease.</p><p id="par0105" class="elsevierStylePara elsevierViewall">The relationship between ON and antimalarial or cytotoxic treatment is controversial. Some authors found no association between taking antimalarials and the presence of ON<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9,18</span></a>; Mok et al. found that patients without ON had been treated with antimalarial at higher rates than <span class="elsevierStyleItalic">those with ON</span>.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> In our series (similar to what was found by Gladman et al.), we found that all patients who had developed ON had received antimalarials, unlike 77% of patients without ON.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> It could be postulated that the activity and severity of SLE itself may predispose to this condition.</p><p id="par0110" class="elsevierStylePara elsevierViewall">In ON has been associated with<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4,6</span></a> vasculitis, Raynaud's phenomenon,<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4,5,8</span></a> neurologic involvement,<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,8</span></a> arthritis<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> superficial thrombophlebitis<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> and with hematuria and proteinuria<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> among others. We did not find any of these relationships in this population.</p><p id="par0115" class="elsevierStylePara elsevierViewall">There is no agreement on whether there is an association between antiphospholipid antibodies and development of ON in patients with SLE. Mont et al.,<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> found a significant association between ON and ACL IgG; Mok et al.,<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> associated it with lupus anticoagulant, and Asherson et al.,<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> observed that patients with antiphospholipid antibodies and ON had received lower doses of steroids than those with ON and negative antiphospholipid antibodies. We, as in other series, found no differences regarding the presence of antiphospholipid antibodies.<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3,8,9,15,17,18</span></a></p><p id="par0120" class="elsevierStylePara elsevierViewall">SLE activity and the use of large doses of steroids at the time of onset of ON or in the year prior to diagnosis of the disease were significantly associated with the presence of ON.<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9,10</span></a> Other authors reported a lack of correlation between activity and ON.<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3,14,17,18</span></a> We found differences between mean SLEDAI of one patient group and another; This can perhaps be explained by the attenuation of high activity scores in the years before the diagnosis of ON and other years with low values of SLEDAI, lack of data or by the small sample size.</p><p id="par0125" class="elsevierStylePara elsevierViewall">The accumulated damage measured by SLICC, excluding the score for ON, was significantly higher for the second year in the group of patients with ON. Other studies have failed to find an association with this variable.<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9,18</span></a></p><p id="par0130" class="elsevierStylePara elsevierViewall">In conclusion, patients with ON mostly presented bilateral hip affection. The cumulative damage at the second year was significantly higher than in patients without ON. This study provides evidence that Cushing's phenotype is the main risk factor for the development of ON in patients with SLE. No relationship to steroid treatment was found that these patients; it may be that they belong to a special group of patients with sensitivity to steroids. When suspecting ON in this population at risk, highly sensitive techniques such as MRI can be used to reach an early diagnosis.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Ethical Responsibilities</span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Protection of people and animals</span><p id="par0135" class="elsevierStylePara elsevierViewall">The authors declare this research did not perform experiments on humans or animals.</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Data privacy</span><p id="par0140" class="elsevierStylePara elsevierViewall">The authors state that no patient data appear in this article.</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Right to privacy and informed consent</span><p id="par0145" class="elsevierStylePara elsevierViewall">The authors state that no patient data appear in this article.</p></span></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Conflicts of Interest</span><p id="par0150" class="elsevierStylePara elsevierViewall">The authors declare no conflicts of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:12 [ 0 => array:3 [ "identificador" => "xres493491" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objectives" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Materials and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec515313" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres493490" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivos" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Materiales y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec515312" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Materials and Methods" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Statistical Analysis" ] ] ] 6 => array:2 [ "identificador" => "sec0020" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "sec0025" "titulo" => "Discussion" ] 8 => array:3 [ "identificador" => "sec0030" "titulo" => "Ethical Responsibilities" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0035" "titulo" => "Protection of people and animals" ] 1 => array:2 [ "identificador" => "sec0040" "titulo" => "Data privacy" ] 2 => array:2 [ "identificador" => "sec0045" "titulo" => "Right to privacy and informed consent" ] ] ] 9 => array:2 [ "identificador" => "sec0050" "titulo" => "Conflicts of Interest" ] 10 => array:2 [ "identificador" => "xack157468" "titulo" => "Acknowledgements" ] 11 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2014-03-14" "fechaAceptado" => "2014-05-21" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec515313" "palabras" => array:3 [ 0 => "Osteonecrosis" 1 => "Systemic lupus erythematosus" 2 => "Steroids" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec515312" "palabras" => array:3 [ 0 => "Osteonecrosis" 1 => "Lupus eritematoso sistémico" 2 => "Esteroides" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objectives</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">To define the proportion of osteonecrosis (ON) in our patient population with lupus and to identify factors associated with the development of ON in systemic lupus erythematosus, as well as to carry out a descriptive analysis of ON cases.</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Materials and methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Observational retrospective study of 158 patients with SLE (ACR 1982 criteria). Demographic and laboratory data, clinical manifestations, SLICC, SLEDAI, cytotoxic and steroid treatments were compared. In patients with ON, we analyzed time of disease progression and age at ON diagnosis, form of presentation, joints involved, diagnostic methods, Ficat–Arlet classification, and treatment. To compare the means, <span class="elsevierStyleItalic">t</span>-test or Mann–Whitney's test was employed and the cHi-2 test or Fisher's exact test, as appropriate, was used to measure the equality of proportions.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">ON was present in 15 out 158 patients (9.5%), 13 women and 2 men, with a mean age of 30 (r: 16–66) at diagnosis and 35 months of evolution until diagnosis (r: 1–195). Among the 15 patients, 34 joints presented ON, 23 were symptomatic and 22 were diagnosed by magnetic resonance images. Twenty-six occurred in hips (24 bilateral), 4 in knees and 4 in shoulders. In 13 patients, ON involved 2 or more joints. At onset, 28 joints were in stage <span class="elsevierStyleSmallCaps">i</span>–<span class="elsevierStyleSmallCaps">ii</span>, one in stage <span class="elsevierStyleSmallCaps">iii</span> and 5 had no data and; in the end, 14 were in stage <span class="elsevierStyleSmallCaps">iii</span>–<span class="elsevierStyleSmallCaps">iv</span>, 5 in stage <span class="elsevierStyleSmallCaps">i</span>–<span class="elsevierStyleSmallCaps">ii</span> and 15 had no data. Twenty-nine underwent conservative treatment with rest and 8 hips required joint replacement. ON progression was associated with Cushing's syndrome (<span class="elsevierStyleItalic">P</span>=0.014) OR 4.16 (95% CI 1.4–12.6) and 2nd year SLICC (<span class="elsevierStyleItalic">P</span>=0.042). No relation with clinical manifestations, lab results, cytotoxic treatment, steroid treatment (total accumulated dose, mean daily dose and duration) metilprednisolone pulses, or activity was found. All patients with ON received antimalarials, in contrast to 77% of those without ON.</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">The proportion of ON was 9.5%, mainly in women, 76% in hips (26) and 92% bilaterally. They were associated significantly with Cushing's syndrome and accumulated damage at second year.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objectives" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Materials and 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">Objetivos</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Definir la proporción de osteonecrosis (ON) en nuestra población lúpica, identificar factores asociados a su desarrollo y realizar un análisis descriptivo de las ON.</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Materiales y métodos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Estudio retrospectivo observacional. Se incluyó a 158 pacientes con lupus eritematoso sistémico (criterios ACR 1982), comparando datos demográficos, de laboratorio, manifestaciones clínicas, SLICC, SLEDAI, tratamiento citotóxico y esteroideo. En pacientes con ON se analizaron el tiempo de evolución y la edad al diagnóstico de ON, la forma de presentación, la articulación comprometida, el método diagnóstico, la clasificación Ficat y Arlet y el tratamiento realizado. Se utilizó la prueba de la t o la prueba de Mann–Whitney para la comparación de medias y para igualdad de proporciones o independencia, la prueba de la chi al cuadrado o exacta de Fisher, según correspondiera.</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">La ON ocurrió en 15/158 pacientes (9,5%), 13 mujeres y 2 hombres. Edad al diagnóstico de ON (mediana): 30 años (r: 16–66) y el tiempo de evolución hasta el diagnóstico de ON: 35 meses (r: 1-195). En los 15 pacientes hubo 34 articulaciones con ON, 23 sintomáticas y 22 diagnosticadas por RM. Veintiséis ON fueron en caderas (24 bilaterales), 4 en rodillas y 4 en hombros. En 13 pacientes la ON afectó a 2 o más articulaciones. Al inicio, 28 articulaciones estaban en estadio <span class="elsevierStyleSmallCaps">i</span>-<span class="elsevierStyleSmallCaps">ii</span>, uno en estadio <span class="elsevierStyleSmallCaps">iii</span> y 5 sin datos y al final, 14 en estadio <span class="elsevierStyleSmallCaps">iii</span>-<span class="elsevierStyleSmallCaps">iv</span>, 5 en estadio <span class="elsevierStyleSmallCaps">i-ii</span> y 15 sin datos. Veintinueve se trataron con reposo y 8 caderas requirieron reemplazo articular. La ON se asoció a aspecto Cushing (p<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0,014), OR 4,16 (IC 95% 1,4-12,6) y SLICC 2.° año (p<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0,042). No hubo relación con manifestaciones clínicas, datos de laboratorio, tratamiento citotóxico o dosis de esteroides ni actividad. Todos los pacientes con ON recibieron antipalúdicos, a diferencia de un 77% de aquellos sin ON.</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">La proporción de ON fue del 9,5%, la mayoría fue en mujeres, el 76% en caderas (26) y el 92% bilateral. Se asociaron significativamente a aspecto Cushing y daño acumulado al segundo año. No se halló relación con el resto de las variables evaluadas.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivos" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Materiales y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Please cite this article as: Gontero RP, Bedoya ME, Benavente E, Roverano SG, Paira SO. Osteonecrosis en lupus eritematoso sistémico. Reumatol Clin. 2015;11:151–155.</p>" ] ] "multimedia" => array:9 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1286 "Ancho" => 1645 "Tamanyo" => 64137 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Cumulative steroid dose (mg), <span class="elsevierStyleItalic">P</span>=.42.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1283 "Ancho" => 1650 "Tamanyo" => 67039 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Average daily steroid dose (mg/day), <span class="elsevierStyleItalic">P</span>=.85.</p>" ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Fig. 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1310 "Ancho" => 1651 "Tamanyo" => 64643 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Total duration of steroid therapy (months), <span class="elsevierStyleItalic">P</span>=.71.</p>" ] ] 3 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:1 [ "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="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Diagnostic method \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">No. joints with ON \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">MRI \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">22 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Rx \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">CT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">MRI<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>Rx \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">MRI<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>bone scan \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab784583.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Method Used for the Diagnosis of Osteonecrosis (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>34).</p>" ] ] 4 => array:7 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:1 [ "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="table-head " align="left" valign="top" scope="col">Affected sites \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">No. of patients</th><th class="td" title="table-head " align="left" valign="top" scope="col">No. of joints \t\t\t\t\t\t\n \t\t\t\t</th></tr><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Unilateral \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Bilateral \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Hips \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">26 (76%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Knees \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4 (12%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Shoulders \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4 (12%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Total \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">34 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab784582.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Patterns of Osteonecrosis in 15 Patients.</p>" ] ] 5 => array:7 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:1 [ "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="table-head " align="left" valign="top" scope="col">Joints: 34 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Ficat and Arlet</th></tr><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Baseline \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Final \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Stage I \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">22 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Stage II \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Stage III \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">6 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Stage IV \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Lack of data \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">15 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab784585.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Classification of Osteonecrosis at the Beginning and at the Last Evaluation.</p>" ] ] 6 => array:7 [ "identificador" => "tbl0020" "etiqueta" => "Table 4" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:1 [ "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="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Joint \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Rest and unloading (# of joints) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Joint replacement (# of joints) \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Hips \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">23 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Shoulders \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Knees \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab784584.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Treatment of Osteonecrosis.</p>" ] ] 7 => array:7 [ "identificador" => "tbl0025" "etiqueta" => "Table 5" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">SLE with ON No.<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>15 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">SLE without ON No.<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>143 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">P</span> \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Age at onset SLE (years), mean<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">28<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>11.72 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">28<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>10,28 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.952 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Gender (women/men) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">13/2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">132/11 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.356 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Time since onset (months), median<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">130<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>82.56 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">106.5<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>95.46 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.356 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">SLEDAI, mean<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2.71<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>2.20 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3.38<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>3.48 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.724 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Diabetes (no. patients) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0/14 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2/128 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Hypothyroidism (no. patients) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2/14 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">21/117 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.999 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Cushing phenotype<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">9/15 (60%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">31/117 (26.5%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.014 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Hypertension \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">6/15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">34/131 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.358 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Alcohol \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1/14 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3/105 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Tobacco use \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2/15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">23/108 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.734 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">% Neoplasia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1/15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">9/113 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Alopecia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4 (27) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">45 (31) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.999 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Malar rash \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">12 (80) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">93 (65) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.389 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Photosensitivity \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">9 (60) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">74 (52) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.543 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Raynaud's \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3 (20) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">41 (27) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.561 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Livedo reticularis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 (7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">7 (5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Mucosal ulcers \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">8 (53) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">50 (35) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.160 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Arthritis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">12 (80) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">111 (78) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.865 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Hip replacement. Jaccoud \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 (7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">6 (4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Renal involvement \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">10 (67) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">69 (48) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.174 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Cardiac involvement \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4 (27) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">43 (30) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.999 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Pulmonary involvement \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">7 (47) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">48 (33) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.311 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Neurological involvement \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2 (13) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">22 (15) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.999 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Myositis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0 (0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 (0.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Vasculitis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3 (20) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">18 (13) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.424 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Thrombosis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2 (13) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">7 (5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.205 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Leukopenia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">8 (53) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">54 (38) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.240 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Lymphopenia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">10 (67) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">76 (53) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.317 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Thrombocytopenia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5 (33) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">31 (22) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.335 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Hemolytic anemia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">6 (40) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">54 (38) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.865 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">FAN (+) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">12/15 (80) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">96/133 (72) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.760 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Anti-nDNA (+) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5/13 (38) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">49/113 (43) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.777 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Anti-Ro (+) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3/12 (25) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">26/72 (36) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.531 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Anti-La (+) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0/9 (0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">12/61 (20) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Anti-Sm (+) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0/7 (0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">18/55 (33) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Anti-RNP (+) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1/6 (17) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">21/51 (41) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">ACL (+) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2/9 (22) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">30/73 (41) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.471 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">LA (+) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2/8 (25) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">12/53 (23) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.999 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab784581.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">OR=4.16 (95% CI, 1.4–12.6).</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">Demographics, Clinical Activity and Antibodies.</p>" ] ] 8 => array:7 [ "identificador" => "tbl0030" "etiqueta" => "Table 6" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:1 [ "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="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">SLICC/ACR damage index \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">SLE with ONMean<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>SD \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">SLE without ONMean<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>SD \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">P</span> \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">1st year \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.60<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.89 (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>13) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.48<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.83 (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>89) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.402 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">2nd year \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.20<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>1.30 (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>13) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.79<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>1.01 (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>82) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.042 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">5th year \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.40<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>1.14 (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>11) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.62<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>1.42 (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>57) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.999 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">10th year \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.80<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.84 (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2.55<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>2.40 (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>29) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.711 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab784580.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">SLICC Accumulated Damage in Patients With and Without Osteonecrosis.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:19 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Risk factors for avascular bone necrosis in systemic lupus erythematosus" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "C.C. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 6 | 16 | 22 |
| 2024 October | 44 | 34 | 78 |
| 2024 September | 34 | 13 | 47 |
| 2024 August | 52 | 35 | 87 |
| 2024 July | 44 | 34 | 78 |
| 2024 June | 55 | 35 | 90 |
| 2024 May | 56 | 45 | 101 |
| 2024 April | 43 | 23 | 66 |
| 2024 March | 31 | 30 | 61 |
| 2024 February | 32 | 30 | 62 |
| 2024 January | 32 | 23 | 55 |
| 2023 December | 23 | 24 | 47 |
| 2023 November | 27 | 33 | 60 |
| 2023 October | 37 | 28 | 65 |
| 2023 September | 82 | 38 | 120 |
| 2023 August | 26 | 18 | 44 |
| 2023 July | 20 | 26 | 46 |
| 2023 June | 29 | 21 | 50 |
| 2023 May | 38 | 23 | 61 |
| 2023 April | 23 | 10 | 33 |
| 2023 March | 48 | 31 | 79 |
| 2023 February | 40 | 32 | 72 |
| 2023 January | 47 | 33 | 80 |
| 2022 December | 61 | 47 | 108 |
| 2022 November | 47 | 36 | 83 |
| 2022 October | 52 | 29 | 81 |
| 2022 September | 34 | 57 | 91 |
| 2022 August | 25 | 72 | 97 |
| 2022 July | 25 | 44 | 69 |
| 2022 June | 28 | 43 | 71 |
| 2022 May | 37 | 38 | 75 |
| 2022 April | 35 | 56 | 91 |
| 2022 March | 53 | 55 | 108 |
| 2022 February | 41 | 35 | 76 |
| 2022 January | 32 | 34 | 66 |
| 2021 December | 29 | 38 | 67 |
| 2021 November | 39 | 53 | 92 |
| 2021 October | 50 | 62 | 112 |
| 2021 September | 32 | 40 | 72 |
| 2021 August | 33 | 48 | 81 |
| 2021 July | 30 | 32 | 62 |
| 2021 June | 44 | 42 | 86 |
| 2021 May | 62 | 40 | 102 |
| 2021 April | 89 | 101 | 190 |
| 2021 March | 85 | 38 | 123 |
| 2021 February | 49 | 26 | 75 |
| 2021 January | 58 | 34 | 92 |
| 2020 December | 44 | 36 | 80 |
| 2020 November | 54 | 24 | 78 |
| 2020 October | 50 | 22 | 72 |
| 2020 September | 49 | 43 | 92 |
| 2020 August | 24 | 33 | 57 |
| 2020 July | 30 | 37 | 67 |
| 2020 June | 58 | 37 | 95 |
| 2020 May | 47 | 31 | 78 |
| 2020 April | 28 | 23 | 51 |
| 2020 March | 23 | 7 | 30 |
| 2018 May | 4 | 1 | 5 |
| 2018 April | 95 | 6 | 101 |
| 2018 March | 121 | 19 | 140 |
| 2018 February | 99 | 5 | 104 |
| 2018 January | 53 | 6 | 59 |
| 2017 December | 98 | 22 | 120 |
| 2017 November | 72 | 7 | 79 |
| 2017 October | 46 | 11 | 57 |
| 2017 September | 57 | 11 | 68 |
| 2017 August | 78 | 6 | 84 |
| 2017 July | 74 | 11 | 85 |
| 2017 June | 89 | 8 | 97 |
| 2017 May | 88 | 11 | 99 |
| 2017 April | 71 | 12 | 83 |
| 2017 March | 55 | 6 | 61 |
| 2017 February | 45 | 10 | 55 |
| 2017 January | 30 | 7 | 37 |
| 2016 December | 83 | 13 | 96 |
| 2016 November | 59 | 12 | 71 |
| 2016 October | 81 | 13 | 94 |
| 2016 September | 64 | 17 | 81 |
| 2016 August | 64 | 8 | 72 |
| 2016 July | 39 | 13 | 52 |
| 2015 December | 3 | 0 | 3 |
| 2015 November | 1 | 17 | 18 |
| 2015 October | 1 | 16 | 17 |
| 2015 September | 2 | 0 | 2 |
| 2015 August | 2 | 15 | 17 |
| 2015 July | 22 | 9 | 31 |
| 2015 June | 52 | 25 | 77 |
| 2015 May | 81 | 35 | 116 |
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