Is there a potential dual effect of denosumab for treatment of osteoporosis and sarcopenia?

BACKGROUND: The prevalence of sarcopenia with osteoporosis results in a higher risk of falling and fractures. It was noted that patients who had completed their planned 5-year denosumab therapy course as treatment for these conditions started to sustain falls. PURPOSE: To assess (a) whether denosumab has a unique dual effect on both bone and muscle in comparison to other anti-resorptive agents and (b) its effectiveness in the follow-up period post-treatment completion compared to other anti-resorptive agents. METHOD: One hundred thirty-five patients diagnosed to have postmenopausal/senile osteoporosis and who were prescribed denosumab were compared to a control group of 272 patients stratified into 2 subgroups - 136 prescribed alendronate and 136 prescribed zoledronate. All patients were assessed for: BMD (DXA), falls risk (FRAS), fracture risk (FRAX), and sarcopenia measures. All were re-assessed after 5 years of denosumab/alendronate therapy and 3 years of zoledronate and 1 year after stopping the osteoporosis therapy. RESULTS: No significant baseline demographic differences between the 3 groups. On completion of the 5-year denosumab therapy, there was significant decrease in falls risk (P = 0.001) and significant improvements in all sarcopenia measures (P = 0.01). One-year post-discontinuation of denosumab, a significant worsening of both falls risk and sarcopenia measures (P = 0.01) noticed. CONCLUSION: Denosumab displayed positive impact and significant improvements in BMD and sarcopenia measures. It also enhanced multidirectional agility as depicted by Timed Up and Go (TUG). Collectively, this would explain the reduction of falls risk which got worse on stopping the medication. Key points • The coexistence of osteoporosis and sarcopenia has been recently considered in some groups as a syndrome termed 'osteosarcopenia'. • Bone and muscle closely interact with each other not only anatomically, but also at the chemical and metabolic levels. • Denosumab displayed positive impact and significant improvements in all sarcopenia measures, and enhanced multidirectional agility with consequent reduction in falls risk. • Denosumab can be considered as a first osteoporosis therapeutic option in this group of patients presenting with osteosarcopenia manifestations.

Role of Interleukin 37 as a Novel Proangiogenic Factor in Juvenile Idiopathic Arthritis.

OBJECTIVE: The aim of this study was to investigate interleukin 37 (IL-37) levels in the serum and synovial fluid of patients with juvenile idiopathic arthritis (JIA), its expression in peripheral blood mononuclear cells, and correlation with disease activity and angiogenesis. METHODS: Seventy JIA patients and 50 control subjects were examined. The Juvenile Arthritis Disease Activity Score in 27 joints (JADAS-27) was calculated. Immunoassays were used to measure the serum and synovial fluid levels of IL-37, vascular endothelial growth factor (VEGF), soluble VEGF receptor 1 (sVEGF-R1), and sVEGF-R2. Relative expression of IL-37 mRNA in peripheral blood mononuclear cells and the power Doppler ultrasound score of the affected joint were measured. RESULTS: Patients with JIA were subdivided as 20 systemic-onset, 20 polyarticular, and 30 oligoarticular (10 persistent, 20 extended) cases. Serum levels of IL-37, VEGF, VEGF-R1, and VEGF-R2 and relative IL-37 mRNA expression were significantly higher in JIA patients when compared with the control subjects (p < 0.001). These concentrations were significantly higher in systemic-onset JIA compared with those in polyarticular and oligoarticular JIA, and in polyarticular JIA when compared with oligoarticular JIA (p < 0.001). Serum, synovial, and mRNA expression levels of IL-37 were positively correlated with C-reactive protein, erythrocyte sedimentation rate, Juvenile Arthritis Disease Activity Score in 27 joints, power Doppler ultrasound score (p < 0.001), and the serum and synovial VEGF and VEGF-RI and -R2 levels (p < 0.05). CONCLUSIONS: Our results demonstrate that IL-37 levels and mRNA expression were significantly increased in JIA patients, and their levels were positively correlated with disease activity and markers of angiogenesis (VEGF and VEGF receptors), suggesting that IL-37 may be correlated with angiogenesis.

Toward Electronic Health Recording: Evaluation of Electronic Patient-reported Outcome Measures System for Remote Monitoring of Early Rheumatoid Arthritis.

OBJECTIVE: To assess the use of electronic patient-reported outcome measures (ePROM) in standard clinical practice for early rheumatoid arthritis (RA) management, the ePROM ability to enhance clinical care, and how computing technology can improve the patients' adherence to therapy. METHODS: In a double-blinded randomized-controlled study, 211 patients with early RA diagnosed according to American College of Rheumatology/European League Against Rheumatism criteria completed a PROM in paper format at their first clinic visit. Patients were then randomized to Group 1, which completed an ePROM questionnaire monthly, or Group 2, which continued the standard paper PROM format. Over a 12-month period, Group 1 patients were assessed every 3 months in the clinic, whereas Group 2 patients were assessed in the clinic initially monthly for 6 months, then every 3 months. The primary endpoint was the equivalence of outcomes [Routine Assessment of Patient Index Data 3 (RAPID-3) and 28-joint Disease Activity Score (DAS28)] in both groups. The secondary endpoint was the patients' adherence to their medications. RESULTS: There was no significant difference between disease activity measures as well as DAS28 and RAPID-3 scores at 3, 6, and 12 months of management, although there was a trend toward lower patient-reported tender joint count and functional disability score in the active group versus the control group. The patients' adherence to antirheumatic therapy was significantly higher (p < 0.01) in the ePROM group, whereas stopping disease-modifying antirheumatic drugs for intolerability was significantly higher (p < 0.01) in the control group at 12 months of treatment. CONCLUSION: We found ePROM equivalent to standard paper PROM format. Further, it enabled the patients to personally monitor how they are doing regarding their disease activity and helped to optimize their adherence to their treatment.