Osteoporosis is a chronic disease characterized by an increased risk of fragility fracture. Patients affected by rheumatic diseases are at greater risk of developing osteoporosis. The purpose of the present review is to discuss the pathogenesis, epidemiology, and treatment of osteoporosis in patients affected by rheumatic diseases with special focus for rheumatoid arthritis, psoriatic arthritis, spondyloarthritis, systemic lupus erythematosus, systemic sclerosis, vasculitides, Sjogren syndrome, and crystal-induced arthritis.

Objective. To investigate predictors of response, remission, low disease activity, damage, and drug discontinuation in patients with systemic lupus erythematosus (SLE) who were treated with belimumab.Methods. In this retrospective study of a multicenter cohort of SLE patients who received intravenous belimumab, the proportion of patients who achieved remission, low disease activity, and treatment response according to the SLE Responder Index 4 (SRI-4) was determined, and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) was used to score disease damage yearly over the follow-up. Predictors of outcomes were analyzed by multivariate logistic regression with the results expressed as odds ratios (ORs) and 95% confidence intervals (95% CIs).Results. The study included 466 patients with active SLE from 24 Italian centers, with a median follow-up period of 18 months (range 1-60 months). An SRI-4 response was achieved by 49.2%, 61.3%, 69.7%, 69.6%, and 66.7% of patients at 6, 12, 24, 36, and 48 months, respectively. Baseline predictors of response at 6 months included a score of ≥10 on the SLE Disease Activity Index 2000 (SLEDAI-2K) (OR 3.14 [95% CI 2.033-4.860]) and a disease duration of ≤2 years . Baseline predictors of response at 12 months included a score of ≥10 on the SLEDAI-2K (OR 3.48 [95% CI 2.004-6.025]) and an SDI score of 0 (OR 1.74 [95% CI 1.036-2.923]). Baseline predictors of response at 24 months included a score of ≥10 on the SLEDAI-2K (OR 4.25 [95% CI 2.018-8.940]) and a disease duration of ≤2 years (OR 3.79 [95% CI 1.039-13.52]). Baseline predictors of response at 36 months included a score of ≥10 on the SLEDAI-2K ) and baseline status of current smoker (OR 0.19 [95% CI 0.039-0.69]). Patients who were in remission for ≥25% of the follow-up period (44.3%) or who had low disease activity for ≥50% of the follow-up period (66.1%) accrued significantly less damage (P = 0.046 and P = 0.007). A baseline SDI score of 0 was an independent predictor of achieving low disease activity in ≥50% of the follow-up period and remission in ≥25% of the follow-up period. Our findings suggest that the lower the baseline damage, the greater the probability of achieving remission over the course of ≥25% of the follow-up. Further, there was a negative association between the number of flares reported prior to belimumab initiation and the frequency of belimumab discontinuation due to inefficacy (P = 0.009).Conclusion. In patients with active SLE and low damage at baseline, treatment with belimumab early in the disease may lead to favorable outcomes in a real-life setting.

No abstract

Bone loss in rheumatoid arthritis (RA) is a key feature both local and systemic. Anti-citrullinated protein antibodies (ACPA) have recently been found to directly induce differentiation and activation of osteoclasts and therefore contribute to periarticular bone loss. The aim of this study was to analyze the effect of ACPA on systemic bone mineral density (BMD) in patients with established RA. This is a cross-sectional study with a single-center RA population. BMD was measured with Dual X-ray absorptiometry at lumbar and femoral sites. ACPA were measured by EIA. Multivariate analysis was performed adjusting for the main confounding variables. One hundred twenty-seven RA patients were enrolled. In univariate analysis, ACPA-positive patients showed lower BMD Z-score (SD below the age- and gender-matched mean reference value) at femoral sites (p < 0.01). A negative correlation between ACPA titer and BMD Z-score at all sites was observed (p < 0.01). The multivariate analysis adjusted for the main confounding variables confirmed the negative effect of ACPA at femoral sites (p < 0.05), but not at lumbar spine BMD. No significant effect of rheumatoid factor has been observed. ACPA have a negative titer-dependent effect on BMD at femoral sites, mainly constituted by cortical bone. ACPA-positive patients, especially if at high titer, should undergo bone investigations and be treated with bone protecting agents. Disease-modifying anti-rheumatic drugs lowering ACPA titer might have positive effects on systemic bone mass.

Mastocytosis is a rare condition characterized by abnormal mast cell proliferation and a broad spectrum of manifestations, including various organs and tissues. Osteoporosis is one of the most frequent manifestations of systemic mastocytosis, particularly in adults. Osteoporosis secondary to systemic mastocytosis is a cause of unexplained low bone mineral density that should be investigated when accompanied by suspicious clinical elements. Bone involvement is often complicated by a high recurrence of fragility fractures, mainly vertebral, leading to severe disability. The mechanism of bone loss is the result of different pathways, not yet fully discovered. The main actor is the osteoclast with a relative or absolute predominance of bone resorption. Among the stimuli that drive osteoclast activity, the most important one seems to be the RANK-RANKL signaling, but also histamine and other cytokines play a significant role in the process. The central role of osteoclasts made bisphosphonates, as anti-resorptive drugs, the most rational treatment for bone involvement in systemic mastocytosis. There are a few small studies supporting this approach, with large heterogeneity of drug and administration scheme. Currently, zoledronate has the best evidence in terms of gain in bone mineral density and bone turnover suppression, two surrogate markers of anti-fracture efficacy.