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Objective To assess the efficacy and safety of abatacept (ABA) in monotherapy (ABAMONO) vs combined ABA [ABA plus MTX (ABAMTX) or ABA plus non-MTX conventional synthetic DMARDs (csDMARDs) (ABANON-MTX)] in RA patients with interstitial lung disease (ILD) (RA-ILD). Methods This was a restrospective multicentre study of RA-ILD Caucasian patients treated with ABA. We analysed in the three groups (ABAMONO, ABAMTX, ABANON-MTX) the following outcome variables: (i) dyspnoea; (ii) forced vital capacity (FVC) and diffusion capacity of the lung for the carbon monoxide (DLCO); (iii) chest high-resolution CT (HRCT); (iv) DAS28-ESR; (v) CS-sparing effect; and (vi) ABA retention and side-effects. Differences between basal and final follow-up were evaluated. Multivariable linear regression was used to assess the differences between the three groups. Results We studied 263 RA-ILD patients (mean ± s.d. age 64.6 ± 10 years) [ABAMONO (n = 111), ABAMTX (n = 46) and ABANON-MTX (n = 106)]. At baseline, ABAMONO patients were older (67 ± 10 years) and took higher prednisone dose [10 (interquartile range 5–15) mg/day]. At that time, there were no statistically significant differences in sex, seropositivity, ILD patterns, FVC and DLCO, or disease duration. Following treatment, in all groups, most patients experienced stabilization or improvement in FVC, DLCO, dyspnoea and chest HRCT as well as improvement in DAS28-ESR. A statistically significant difference between basal and final follow-up was only found in CS-sparing effect in the group on combined ABA (ABAMTX or ABANON-MTX). However, in the multivariable analysis, there were no differences in any outcome variables between the three groups. Conclusion In Caucasian individuals with RA-ILD, ABA in monotherapy or combined with MTX or with other conventional-DMARDs seems to be equally effective and safe. However, a CS-sparing effect is only observed with combined ABA.

The term osteomalacia (OM) refers to a series of processes characterized by altered mineralization of the skeleton, which can be caused by various disorders of mineral metabolism. OM can be genetically determined or occur due to acquired disorders, among which the nutritional origin is particularly relevant, due to its wide epidemiological extension and its nature as a preventable disease. Among the hereditary diseases associated with OM, the most relevant is X-linked hypophosphatemia (XLH), which manifests in childhood, although its consequences persist into adulthood where it can acquire specific clinical characteristics, and, although rare, there are XLH cases that reach the third or fourth decade of life without a diagnosis. Some forms of OM present very subtle initial manifestations which cause both considerable diagnosis and treatment delay. On occasions, the presence of osteopenia and fragility fractures leads to an erroneous diagnosis of osteoporosis, which may imply the prescription of antiresorptive drugs (i.e., bisphosphonates or denosumab) with catastrophic consequences for OM bone. On the other hand, some radiological features of OM can be confused with those of axial spondyloarthritis and lead to erroneous diagnoses. The current prevalence of OM is not known and is very likely that its incidence is much higher than previously thought. Moreover, OM explains part of the therapeutic failures that occur in patients diagnosed with other bone diseases. Therefore, it is essential that clinicians who treat adult skeletal diseases take into account the considerations provided in this practical review when focusing on the diagnosis and treatment of their patients with bone diseases.

To estimate the incidence of clinical fragility fractures in postmenopausal women with rheumatoid arthritis (RA) and analyze risk factors for fracture.Incidence of clinical fragility fractures in 330 postmenopausal women with RA was compared to that of a control population of 660 age-matched postmenopausal Spanish women. Clinical fractures during the previous five years were recorded. We analyzed associations with risk factors for fracture in both populations and with disease-related variables in RA patients.Median age of RA patients was 64 years; median RA duration was eight years. Sixty-nine percent were in remission or on low activity. Eighty-five percent had received glucocorticoids (GCs); 85 %, methotrexate; and 40 %, ≥1 biologic DMARD. Fifty-four patients and 47 controls had ≥1 major osteoporotic fracture (MOF). Incidence of MOFs was 3.55 per 100 patient-year in patients and 0.72 in controls (HR: 2.6). Risk factors for MOFs in RA patients were age, previous fracture, parental hip fracture, years since menopause, BMD, erosions, disease activity and disability, and cumulative dose of GCs. Previous fracture in RA patients was a strong risk for MOFs (HR: 10.37).Of every 100 postmenopausal Spanish women with RA, 3-4 have a MOF per year. This is more than double that of the general population. A previous fracture poses a high risk for a new fracture. Other classic risk factors for fracture, RA disease activity and disability, and the cumulative dose of GCs are associated with fracture development.

To describe practice patterns, long-term outcome, and related factors, in relation to biological therapies tapering in rheumatoid arthritis (RA) patients in a well-controlled real-world setting.An observational longitudinal retrospective 10-year study was conducted in all RA patients receiving biological agents in an RA clinic from May 2003 to October 2013. Biological treatment of patients with sustained DAS283.2 or SDAI11 was tapered (dose down-titrated or interval widen) or discontinued as per practice protocol. Primary outcome of tapering was relapse, defined as an increase in DAS28≥1.2. Descriptive, survival analysis, and logistic regression analysis with first relapse as dependent variable were carried out.Of 193 RA patients on biological treatment (mean age 54±14 years, 81% women), tapering was applied in 106 (55%) and discontinuation in 34 (17.6%). During follow-up 38 patients relapsed (62%). Rate of relapse was 10% at 6 months, 19% at 12 months, 33.2% at 2 years and 50% after 5 years. Mean time in dose reduction was 4.5 years [95% confidence interval (95% CI): 3.7-5.3]. Six patients (15.7%) did not respond after reinstatement of full dose of biologic. In the multivariate analysis, pain [OR=1.26 (95% CI: 1.11-1.43); P.001] and erythrocyte sedimentation rate (ESR) [OR=1.01 (95% CI: 1.00-1.03); P=.011] at baseline were associated with relapse after tapering.Tapering may be considered a long-term option in RA patients on biologics and low disease activity, especially if low ESR and pain scores are present at baseline; treatment reinstatement could be considered a safe option in case of relapse.

ObjectiveThe Assessment of SpondyloArthritis international Society Health Index (ASAS HI) is a tool designed to assess disease impact in spondyloarthritis (SpA), but its clinical performance is barely known. We aimed to test the clinimetric properties of ASAS HI in a real clinical setting.MethodsThis cross-sectional study included 111 consecutive patients with SpA. The measurement properties of ASAS HI were tested against conventional assessment measures. Convergent validity was assessed by Spearman rho correlations, while discriminative validity was analyzed through receiver-operating characteristic (ROC) curves. A multivariate regression analysis was designed to identify ASAS HI items associated with active disease.ResultsThe average ASAS HI was 5.4 ± 3.8 (interquartile range 3–8). ASAS HI showed high convergent validity against other SpA measures (rho ≥ 0.70, p < 0.0005). The optimal criteria for detecting high/very high disease activity Ankylosing Spondylitis Disease Activity Score (ASDAS) categories was an ASAS HI score > 6, area under the ROC curve 0.86 (95% CI 0.78–0.92), positive likelihood ratio 7.3 (95% CI 3.1–17.1), p < 0.0001. The ASAS HI items significantly associated with Bath Ankylosing Spondylitis Disease Activity Index active disease were “I often get frustrated” (OR 9.2, 95% CI 1.2–69.4, p = 0.032), and “I sleep badly at night” (OR 7.7, 95% CI 1.4–41.6, p = 0.018). As for ASDAS, it was “pain sometimes disrupts my normal activities” (OR 8.7, 95% CI 1.7–45.2, p = 0.010).ConclusionThe ASAS HI is a useful and simple instrument for its application in daily practice. Given its good clinimetric properties, it could be used as an additional instrument to evaluate SpA.

Elderly psoriatic arthritis (PsA) patients may show greater inflammatory activity and worse prognoses than patients of other ages. However, these patients may be at risk of receiving fewer systemic treatments. In this report, we have analysed disease outcomes in PsA by age groups.This cross-sectional, multicentre study included 227 PsA patients under biological and non-biological systemic therapies. The study population was divided into four categories by age: 40, 40‒49, 50‒65 and 65 years. Physical functioning, disease activity, remission rates and disease impact were compared.Thirty-one patients (13.7%) were under 40 years, 26.9% (n = 61) were 40-49 years, 26.4% (n = 60) were 50-65 years and 33.0% (n = 75) were patients 65 years. Compared with the other age groups, disease duration was significantly higher in subjects older than 65 years (p 0.001). Only 8% of patients older than 65 years received corticosteroids compared with 29% of patients aged 40 years, 13.1% of patients aged 40-49 years and 26.7% of patients aged 50-65 years (p = 0.007). Similarly, only 36% of patients over 65 years of age received a biological therapy compared with between 51.6 and 59% for the other age groups (p = 0.036). However, remission rates were not statistically different between groups. Disease-associated physical disability was similar among groups. Compared with patients aged 40 years, more patients 65 years achieved low disease impact (10.7% vs 37.7%, respectively; p 0.05).Fewer older patients received corticosteroids and biological therapy. However, disease outcomes were similar or even better compared with those observed in younger patients. Therefore, treatment strategies for older patients with PsA should be similar to those offered to younger individuals.

Objective To update the recommendations on osteoporosis (OP) of the Spanish Society of Rheumatology (SER) based on the best possible evidence. Methods A panel of nine expert rheumatologists in OP was created, previously selected by the SER through an open call. The phases of the work were: identification of the key areas for updating the previous consensus, analysis and synthesis of the scientific evidence (using the SIGN levels of evidence) and formulation of recommendations based on this evidence and consensus techniques. Results This revision of the recommendations implies an update in the diagnostic evaluation and treatment of OP. It proposes some criteria to consider the high risk of fracture and some indications to start treatment. The recommendations also address issues related to the safety of treatments and the management of special situations such as inflammatory diseases and treatment with glucocorticoids. Conclusions We present an update of SER recommendations on OP.

To update the recommendations on osteoporosis (OP) of the Spanish Society of Rheumatology (SER) based on the best possible evidence.A panel of nine expert rheumatologists in OP was created, previously selected by the SER through an open call. The phases of the work were: identification of the key areas for updating the previous consensus, analysis and synthesis of the scientific evidence (using the SIGN levels of evidence) and formulation of recommendations based on this evidence and consensus techniques.This revision of the recommendations implies an update in the diagnostic evaluation and treatment of OP. It proposes some criteria to consider the high risk of fracture and some indications to start treatment. The recommendations also address issues related to the safety of treatments and the management of special situations such as inflammatory diseases and treatment with glucocorticoids.We present an update of SER recommendations on OP.

Prevalence and risk factors of vertebral fractures in postmenopausal RA women were assessed in 323 patients and compared with 660 age-matched women. Of patients, 24.15% had at least one vertebral fracture vs.16.06% of controls. Age, glucocorticoids and falls were the main fracture risks. Vertebral fractures were associated with disease severity. Introduction There is little quality data on the updated prevalence of fractures in rheumatoid arthritis (RA) that may have changed due to advances in the therapeutic strategy in recent years. This study was aimed at analysing the prevalence and risk factors of vertebral fractures in postmenopausal women with RA and comparing it with that of the general population. Methods We included 323 postmenopausal women diagnosed with RA from 19 Spanish Rheumatology Departments, randomly selected and recruited in 2018. Lateral radiographs of the thoracic and lumbar spine were obtained to evaluate morphometric vertebral fractures and the spinal deformity index. We analysed subject characteristics, factors related to RA, and fracture risk factors. The control group consisted of 660 age-matched Spanish postmenopausal women from the population-based Camargo cohort. Results Seventy-eight (24.15%) RA patients had at least one vertebral fracture. RA patients had increased fracture risk compared with controls (106 of 660, 16.06%) (p = 0.02). Logistic regression analysis showed that age (OR 2.17; 95% CI 1.27-4.00), glucocorticoids (OR 3.83; 95% CI 1.32-14.09) and falls (OR 3.57; 95% CI 1.91-6.86) were the independent predictors of vertebral fractures in RA patients. The subgroup with vertebral fractures had higher disease activity (DAS28: 3.15 vs. 2.78, p = 0.038) and disability (HAQ: 0.96 vs. 0.63, p = 0.049), as compared with those without vertebral fractures. Conclusion The risk of vertebral fracture in RA is still high in recent years, when compared with the general population. The key determinants of fracture risk are age, glucocorticoids and falls. Patients with vertebral fractures have a more severe RA.

Objective To assess the efficacy of abatacept (ABA) in RA patients with interstitial lung disease (ILD) (RA-ILD). Methods This was an observational, multicentre study of RA-ILD patients treated with at least one dose of ABA. ILD was diagnosed by high-resolution CT (HRCT). We analysed the following variables at baseline (ABA initiation), 12 months and at the end of the follow-up: Modified Medical Research Council (MMRC) scale (1-point change), forced vital capacity (FVC) or diffusion lung capacity for carbon monoxide (DLCO) (improvement or worsening ≥10%), HRCT, DAS on 28 joints evaluated using the ESR (DAS28ESR) and CS-sparing effect. Results We studied 263 RA-ILD patients [150 women/113 men; mean (s.d.) age 64.6 (10) years]. At baseline, they had a median duration of ILD of 1 (interquartile range 0.25–3.44) years, moderate or severe degree of dyspnoea (MMRC grade 2, 3 or 4) (40.3%), FVC (% of the predicted) mean (s.d.) 85.9 (21.8)%, DLCO (% of the predicted) 65.7 (18.3) and DAS28ESR 4.5 (1.5). The ILD patterns were: usual interstitial pneumonia (UIP) (40.3%), non-specific interstitial pneumonia (NSIP) (31.9%) and others (27.8%). ABA was prescribed at standard dose, i.v. (25.5%) or s.c. (74.5%). After a median follow-up of 12 (6–36) months the following variables did not show worsening: dyspnoea (MMRC) (91.9%); FVC (87.7%); DLCO (90.6%); and chest HRCT (76.6%). A significant improvement of DAS28ESR from 4.5 (1.5) to 3.1 (1.3) at the end of follow-up (P Conclusion ABA may be an effective and safe treatment for patients with RA-ILD.

The performance of many outcome measures for psoriatic arthritis (PsA) is almost unknown in real clinical practice. Our objective was to study the correlation and sensitivity to change of the Disease Activity in Psoriatic Arthritis (DAPSA) index and the Psoriatic Arthritis Impact of Disease (PsAID) questionnaire in a real practice setting.This was a prospective, open, non-controlled study that included 60 consecutive patients with PsA treated with ustekinumab. Most had been previously treated with one or more biologic therapeutic agents. The correlation (Spearman's rho coefficient) and the sensitivity to change [Standardized Mean Response (SMR)] of DAPSA and PsAID were studied. Effect size values of 0.20, 0.50 and 0.80 corresponded to low, moderate and high sensitivity to change, respectively.More than 70% of patients achieved therapeutic goals (21.7% were in remission and 50% in low disease activity according to DAPSA categories). Two out of three patients reached an acceptable symptomatic state (PsAID4). The correlation between final values of both instruments was substantial (Spearman's rho: 0.62, p0.0001). The SMR for the PsAID was 1.08 (0.95-1.21) and for DAPSA was 1.5 (1.37-1.63), both values corresponding to instruments with a high sensitivity to change (0.80). The best PsAID cut-off value for identifying DAPSA remission was 3.32 with an area under the ROC curve of 0.82.DAPSA and PsAID seem to be useful instruments for a more comprehensive assessment of PsA in daily practice. Our results can help to disseminate the use of these instruments in the clinical practice of many rheumatologists.

OBJECTIVE: Interstitial lung disease (ILD) is one of the most serious complications of rheumatoid arthritis (RA). In the present study, we aimed to assess the efficacy of abatacept (ABA) in patients with ILD associated to RA. METHODS: National multicenter, non-controlled, open-label registry study of RA patients with ILD treated with ABA. RESULTS: 63 patients (36 women) with RA-associated ILD undergoing ABA therapy were studied. The mean ± standard deviation age at the time of the study was 63.2 ± 9.8 years. The median duration of RA and ILD from diagnosis were 6.8 and 1 year, respectively. RA was seropositive in 55 patients (87.3%). In 15 (23.8%) of 63 patients the development of ILD was closely related to the administration of synthetic or biologic disease modifying anti-rheumatic drugs. After a follow-up of 9.4 ± 3.2 months, two-thirds of patients remained stable whereas one-quarter experienced improvement in the Modified Medical Research Council scale. At that time forced vital capacity remained stable in almost two-thirds of patents and improved in one out of five patients assessed. Also, diffusing capacity of the lung for carbon monoxide remained stable in almost two-thirds and showed improvement in a quarter of the patients assessed. At 12 months, 50% of the 22 patients in whom chest HRCT scan was performed due persistence of respiratory symptoms showed stabilization, 8 (36.4%) improvement and 3 worsening of the HRCT scan pattern. Eleven of 63 patients had to discontinue ABA, mainly due to adverse events. CONCLUSION: ABA appears to be an effective in RA-associated ILD. Funding: This work was partially supported by RETICS Programs, RD08/0075 (RIER) and RD12/0009/0013 from ‘‘Instituto de Salud Carlos III’’ (ISCIII), Spain.

Pyle's disease (OMIN number 265900) is a metaphyseal dysplasia of benign course, inherited with an autosomal recessive pattern. Some 30 genuine cases have been described so far. The cause of this process has been known since 2016, when its relationship to mutations in the gene encoding the sFRP protein, a known inhibitor of the Wnt pathway, was discovered. We report the case of a 58-year-old man, diagnosed with Pyle's disease based on his clinical and radiographic characteristics, whose phenotype suggested a differential control of cortical and trabecular bone homeostasis.

Cogan's syndrome is a rare autoimmune disease that usually affects young Caucasian adults and is classically defined as the combination of nonsyphilitic interstitial keratitis and audiovestibular symptoms resembling Meniere's disease, both of them developed in an interval of less than two years. Nevertheless, cases with atypical ophthalmologic and audiovestibular features, with systemic manifestations or affecting children and older patients have also been reported, expanding the clinical spectrum of Cogan's syndrome. Herein, we present the case of a late-onset Cogan's syndrome associated with a large-vessel vasculitis.

Resumen El tejido oseo es una estructura fuertemente regulada, que desempena un papel esencial en diferentes funciones fisiologicas. A traves de acciones autocrinas y paracrinas participa en la hematopoyesis, influyendo en el destino de las celulas madre hematopoyeticas. Existe ademas una serie de moleculas compartidas y tambien multiples conexiones entre el sistema inmune y el tejido oseo. Con el objetivo de agrupar los conocimientos que relacionan ambos sistemas, se ha desarrollado una nueva disciplina conocida con el termino «osteoinmunologia». Su progresion en los ultimos anos ha sido exponencial y nos ha permitido relacionar e incrementar el conocimiento en temas aparentemente alejados como la erosion reumatoide, la osteoporosis posmenopausica, las metastasis oseas o la enfermedad periodontal. En la presente revision hemos tratado de resumir los avances mas relevantes que se han producido en la ultima decada, sobre todo en aquellos aspectos que interesan de manera preferente a la reumatologia.

This study was conducted to investigate the presence and characteristics of the ultrasound lesions that may be found in the entheses of patients with SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis) syndrome. This cross-sectional study included 15 patients with SAPHO syndrome and 30 healthy controls matched for age, sex and body mass index. Subjects with regular sport activities as well as those with other rheumatic conditions were excluded from the study. Ultrasonography was used in both groups to study 14 entheses of the upper and lower extremities. Different elementary lesions representative of enthesis damage were defined. A total of 210 entheses in the study group and 420 in the control group were evaluated. Only one patient presented clinical enthesitis. In the study group, seven of the 15 patients (47%) showed morpho-structural entheseal alterations, versus only four of the 30 controls (13.3%; p

Objective Due to increasing improvement in the diagnosis, evaluation and management of osteoporosis and the development of new tools and drugs, the Spanish Society of Rheumatology (SER) has promoted the development of recommendations based on the best evidence available. These recommendations should be a reference to rheumatologists and other health professionals involved in the treatment of patients with osteoporosis. Methods Recommendations were developed following a nominal group methodology and based on a systematic review. The level of evidence and the degree of recommendation were classified according to the model proposed by the Center for Evidence Based Medicine at Oxford. The level of agreement was established through Delphi technique. Evidence from previous consensus and available clinical guidelines was used. Results We have produced recommendations on diagnosis, evaluation and management of osteoporosis. These recommendations include the glucocorticoid-induced osteoporosis, premenopausal and male osteoporosis. Conclusions We present the SER recommendations related to the biologic therapy risk management.

Resumen Objetivo Dado el creciente avance en el diagnostico como evaluacion y tratamiento de la osteoporosis, y la incorporacion de nuevas herramientas y medicamentos, desde la Sociedad Espanola de Reumatologia (SER) se ha impulsado el desarrollo de recomendaciones basadas en la mejor evidencia posible. Estas deben de servir de referencia para reumatologos y otros profesionales de la salud implicados en el tratamiento de pacientes con osteoporosis. Metodos Las recomendaciones se emitieron siguiendo la metodologia de grupos nominales. El nivel de evidencia y el grado de recomendacion se clasificaron segun el modelo del Center for Evidence Based Medicine de Oxford y el grado de acuerdo se extrajo por tecnica Delphi. Se utilizo toda la informacion de consensos previos y guias de practica clinica disponibles. Resultados Se realizan recomendaciones sobre el diagnostico, la evaluacion y el tratamiento en pacientes con osteoporosis. Estas recomendaciones incluyen la osteoporosis secundaria a glucocorticoides, la osteoporosis premenopausica y la del varon. Conclusiones Se presentan las recomendaciones SER sobre el diagnostico, la evaluacion y el manejo de pacientes con osteoporosis.

Chronic renal failure (CRF) is frequent in patients with osteoporosis and the rheumatologist should be familiarized with basic diagnostic and treatment guidelines for bone mineral disease associated to this process. In patients with osteoporosis and stage I and II CRF, diagnosis and treatment does not vary from that in patients with normal RF. In stage III CRF, the focus will depend on the result of testing. In advanced stage CRF the approach should be coordinated with a nephrologist. In these cases it is possible to use antiresorptive agents although in well-selected and studied patients. The present review analyzes recent advances in this field with a focus on daily clinical practice.

Los aminobisfosfonatos son farmacos que han sido utilizados con exito en el tratamiento de la osteoporosis desde hace mas de 20 anos. Aunque en los estudios principales realizados para obtener la aprobacion de su comercializacion no se registraron efectos adversos relevantes, en los ultimos anos, y como resultado de la farmacovigilancia, se ha comunicado de manera irregular una serie de complicaciones, algunas potencialmente graves, que han puesto en duda la seguridad de estos farmacos, sobre todo en dosis elevadas como las que se utilizan en oncologia y en tratamientos de larga duracion, como los que se emplean en la osteoporosis. En la presente revision, basada en el analisis de las pruebas cientificas mas relevantes procedentes de los ensayos clinicos, series de casos, estudios de cohortes y bases de datos publicados hasta el momento, se resumen las caracteristicas clinicas y epidemiologicas de los efectos adversos de los bisfosfonatos

Dropped head syndrome (DHS) occurs in patients with severe weakness of the neck extensor muscles, of diverse origin, but most frequently because of neuromuscular diseases. Exceptionally, DHS may be the first manifestation of a systemic autoimmune disease. This report describes the case of a patient with DHS as a presenting sign of scleromyositis. We analyze the clinical features of the case and discuss the most important aspects of its pathogenesis and differential diagnosis.

AA amyloidosis, or secondary amyloidosis, is a rare but serious complication of chronic inflammatory diseases. Chronic inflammatory arthritis is the commonest cause of AA amyloidosis and, when the latter appears, treatment can be frustrating. Deposition of fibrils, derived from circulating acute-phase reactant serum amyloid A protein (SAA), in the kidneys can lead to proteinuria and progressive loss of renal function. We describe the case of a 14-year-old female with systemic juvenile idiopathic arthritis who developed nephrotic syndrome secondary to AA amyloidosis; while she was unresponsive to all measures, including anti-tumour necrosis factor therapy, treatment with tocilizumab, an anti-human interleukin-6 receptor antibody, immediately normalized the SAA and reversed the nephrotic syndrome. We discuss this new therapeutic approach.

secondly, not even the protective effect of aspirin, that in clinically controlled trials was found to have a maximal reduction close to 30%, could explain the magnitude in the excess risk for MI observed in those exposed to rofecoxib in VIGOR. The withdrawal of rofecoxib in 2004 was motivated by the results of another study, APPROVe, which was not specifically designed to evaluate cardiovascular safety of the drug, but to study its hypothetical protective effect against the recurrence of intestinal polyps. 8 This study was prematurely stopped due to an excess in the atherothrombotic events in the group with rofecoxib, compared to the placebo group. Nonetheless, another clinical trial in patients with Alzheimer did not show an increase in the cardiovascular risk associated with this The cardiovascular safety profile of non-steroidal anti- inflammatory drugs (NSAID) is being questioned since the publication of the results of several clinical trials and observational studies. True, at the beginning research focused exclusively on selective inhibitors of cyclo- oxygenase 2 (COX-2, also known as coxib, but the results of some recent studies indicate that the increase in the risk of cardiovascular disease could more or less be shared with some traditional NSAID (NSAIDt). The use of NSAID has been associated with a larger risk of hipertension 1 and heart failure, 2,3 and its possible association with the development of atherothrombotic disease emerged towards the end of the nineties. In 2000 the first epidemiological study that showed a small increment in the risk of myocardial infarction (MI) associated with the chronic use of NSAIDt was published. 4 Around the same time, coxibs started to be commercialized worldwide. The unexpected rise in the cardiovascular risk observed in patients that had been treated with high doses of rofecoxib in the VIGOR 5 study, together with the results of 2 other previous pharmacologic studies on coxibs 6,7 seemed to point at a class effect regarding cardiovascular damage, as a consequence of the suppression of prostacyclin in the absence of thromboxane A 2 (TXA 2 ) inhibition. In this way, a selective inhibition of COX-2 could reduce the cardioprotective effects of prostacyclin in the vascular endothelium, whose synthesis of mediated by this enzyme, without inhibiting the proaggregation effects of TXA 2 , whose production is primarily controlled by the isoenzyme cyclo-oxygenase 1 (COX-1). Nonetheless, there where those who postulated that the observed result did not correspond to a rofecoxib-associated increment in the risk, but to a hypothetical cardioprotective effect of the drug it was being compared to, namely naproxen, because this NSAID has a long half-life and a greater affinity for COX-1 in a reversible manner, different from aspirin which irreversibly acetylates the enzyme and

Bone tissue is a highly regulated structure, which plays an essential role in various physiological functions. Through autocrine and paracrine mechanisms, bone tissue is involved in hematopoiesis, influencing the fate of hematopoietic stem cells. There are a number of molecules shared by bone cells and immune system cells indicating that there are multiple connections between the immune system and bone tissue. In order to pool all the knowledge concerning both systems, a new discipline known under the term «osteoimmunology» has been developed. Their progress in recent years has been exponential and allowed us to connect and increase our knowledge in areas not seemingly related such as rheumatoid erosion, postmenopausal osteoporosis, bone metastases or periodontal disease. In this review, we have tried to summarize the most important advances that have occurred in the last decade, especially in those areas of interest related to rheumatology.

The main objective of this work was to evaluate the characteristics of sleep in patients diagnosed with fibromyalgia syndrome. Sleep architecture in 32 patients with fibromyalgia and 20 healthy controls was evaluated. Following the recommendations of the International Federation of Clinical Neurophysiology, polysomnographies were conducted with fibromyalgia patients and the control subjects. The fibromyalgia patients showed alterations in cyclic organization of sleep and an increased number of periodic leg movements associated with cortical arousals. No significant differences were found in respiratory and oximetry variables or in alpha-delta sleep. The results support that fibromyalgia patients present an increase of superficial sleep at the expense of deep sleep and also an increase of periodic leg movements, which could have a pathogenic effect, facilitating the onset of the illness. Lastly, we discuss the results and propose some future lines of research.

Chronic renal failure (CRF) is frequent in patients with osteoporosis and the rheumatologist should be familiarized with basic diagnostic and treatment guidelines for bone mineral disease associated to this process. In patients with osteoporosis and stage I and II CRF, diagnosis and treatment does not vary from that in patients with normal RF. In stage III CRF, the focus will depend on the result of testing. In advanced stage CRF the approach should be coordinated with a nephrologist. In these cases it is possible to use antiresorptive agents although in well-selected and studied patients. The present review analyzes recent advances in this field with a focus on daily clinical practice.

Aminobisphosphonates are drugs that have been used successfully in the treatment of osteoporosis for more than 20 years. Although main registry studies found a scarcity of relevant adverse events, in recent years and as a result of pharmacovigilance, different complications have been reported, some potentially serious. This has raised questions on the safety of these drugs, especially in high doses, like those used in oncology and long-term treatment, as needed in patients with osteoporosis. In this review, based on the analysis of relevant scientific evidence from clinical trials, case series, cohort studies and databases published to date, we summarize the clinical and epidemiological characteristics of the adverse effects of these drugs.

Background and aims: Vertebral fracture (VF) is the most common complication of osteoporosis. However, more than half of all VF are asymptomatic and may go unnoticed, even in patients with osteoporosis. Our aim was to assess the prevalence of VF in postmenopausal women with osteopenic lumbar densitometry by means of vertebral morphometry, using the MorphoXpressSR software. Patients and methods: This was an epidemiological, cross-sectional, multicenter study conducted among 289 postmenopausal women (>1 year of amenorrhoea), diagnosed with lumbar osteopenia (not due to chronic treatment with corticosteroids or immobilization). Vertebral deformities ≥20% were considered as VF. Results: Demographic and clinical characteristics showed mean age (±SD) 64±9 years, body mass index 27±5 kg/m2, and time from diagnosis of 2±3 years. A total of 25% of subjects had a family history of osteoporotic fracture in first-degree relatives, and 23% had previous fragility fracture. The prevalence of VF was 50% (CI 95% 44–56), the most frequent being the dorsal wedge (34%). Previous fragility fracture was a risk factor for VF (OR 3.13, p=0.0004). A total of 76.5% of patients were receiving treatment, mainly calcium and vitamin D supplements (70%) and bisphosphonates (27%). Conclusions: MorphoXpressSR revealed that 50% of postmenopausal women with osteopenic lumbar densitometry showed VF. This result is important since only 7% of all evaluated subjects had previously been diagnosed with VF.

To the Editor: Rheumatoid arthritis (RA) is a complex disease with a strong immune inflammatory component. Recent progress in defining the role of genetic factors in RA has been remarkable. It has been proposed that the shared epitope (SE) is a primary genetic element of susceptibility. Citrullination is a post-translational protein modification that is accomplished by deimination of arginine by peptidyl-arginine deiminases. Interestingly, polymorphisms in one member of the family, PADI4, have been associated with RA in Asian populations1, although this association could not be reproduced in Caucasian populations2,3. An association has been described between the presence of the SE and anti-cyclic citrullinated peptide antibody (anti-CCP) levels, and of each variable with disease severity4,5. Also, anti-CCP-positive has been reported to be immunogenetically distinct from anti-CCP-negative disease, with the former subgroup being primarily responsible for association and linkage to HLA-DRB1 SE6. In this cross-sectional study we aimed at analyzing whether the presence of the SE and anti-CCP caused an acceleration in disease development that could be reflected in an earlier age at onset. This acceleration might be considered a sign of a worse prognosis. We analyzed 411 Spanish patients with RA … Address reprint requests to Dr. Martinez. E-mail: alfmdoncel{at}terra.es