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.

Incorporating motivational interviewing into rheumatology care.

Deborah Palmer, Advanced Nurse Practitioner, North Middlesex University Hospital, and Yasser El Miedany, Consultant Rheumatologist, discuss ways to close the gap between disease control and patient empowerment.

Association of Paraoxonase 1 Polymorphism and Serum 25-Hydroxyvitamin D with the Risk of Cardiovascular Disease in Patients with Rheumatoid Arthritis.

BACKGROUND: Patients with rheumatoid arthritis (RA) have significantly increased cardiovascular (CV) morbidity and mortality that are not accounted for by traditional risk factors alone. Paraoxonase 1 (PON1) and 25-hydroxyvitamin D have been shown to be involved in the pathogenesis of CV diseases. Objective: This study aimed to investigate PON1 gene polymorphism and serum 25-hydroxyvitamin D concentrations in RA patients, and to determine their association with CV risk in RA. METHODS: Serum samples from 46 RA patients and 45 healthy controls were tested for PON1 R192Q genotypes and serum vitamin D concentrations. The cardiovascular risks were assessed by Q-risk. Lipoprotein cholesterol levels, traditional CV risk factors, medication use, and RA disease activity status were also assessed. RESULTS: PON1 polymorphism and low serum 25-hydroxyvitamin D were significantly associated with increased CV risk (p < 0.05). Compared to patients with either the PON1 QQ genotype or the QR genotype, patients with the RR genotype demonstrated decreased CV risk on multivariate analysis, controlling for traditional CV risk factors, C-reactive protein levels, prednisone use, and cholesterol-lowering medication use (p < 0.05). CONCLUSIONS: There was a relationship of the genetic determinants of paraoxonase 1 (PON1 192) and serum 25-hydroxyvitamin D to CV risk in RA patients. Paired measurement of paraoxonase 1 genotype and serum 25-hydroxyvitamin D can be used as biomarkers of CV risk in RA patients.

Treat to target in spondyloarthritis: the time has come.

Recent publications have proposed revisions to disease classification criteria, new definitions of early diagnosis and remission, as well as guidelines for implementing treat-to-target strategies for the management of patients with spondyloarthritis. Despite developments leading to this practice-changing approach, the concept of treat to target for spondyloarthritis has not yet been widely accepted or implemented in standard clinical care. By placing greater emphasis on clinical features that manifest early in the disease process, the early and aggressive treatment of the most common forms of spondyloarthritis (namely ankylosing spondylitis and psoriatic arthritis), has been shown to have favorable patient outcomes in reducing synovial inflammation, delaying joint damage, and maintaining functional status. This article discusses the recent concept of Treat to Target in spondyloarthritis and the importance of early diagnosis of both ankylosing spondylitis (AS) and psoriatic arthritis (PsA). It also highlights the main outcome measures for spondyloarthritis patients achieving treatment goals of low levels of disease activity or clinical remission.

Treat to target for osteoporosis: another step forward.

Monitoring treatment effects can inform both the physician and patient whether the medication has achieved its anticipated targets. There are several variances between patients cohorts included in clinical trials and subjects managed in standard clinical setting. Therefore, defining a patient as a "responder" or "non-responder" to management might not be applicable in day to day care, in particular in patients suffering from chronic diseases. So far, in patients receiving treatment for osteoporosis, there is no clear guidance on when the fracture risk has been reduced to an acceptable low level. As a consequence, some patients at low risk for fracture may have continued their treatment for longer periods than necessary, whereas others at high risk for fracture may have their treatment stopped whilst the continuation of the same medication or a change to a more potent therapy might be of value. In many specialties, goal-directed treating to target is already the standard and the time has come for goal-directed management of osteoporosis. Adopting treat-to-target approach in osteoporosis has the prospective of developing the patients' care, plummeting the osteoporotic fractures burden, in addition to having a positive cost-effectiveness impact. This article aims at discussing the potential utility of "treat-to-target" approach for osteoporotic patients management in standard clinical practice. It also includes a suggested algorithm for long term osteoporosis treatment as well as post-drug holiday management based on "treat to target" strategy.