• Metabolic Bone Disease
• Rheumatoid Arthritis
• Lupus Clinical Trials

• Metabolic Bone Disease
• Rheumatoid Arthritis
• Rheumatology
• Lupus
• Rheumatology Clinical Trials

Although glucocorticoids (GCs) are a backbone of the treatment of rheumatic diseases, they are the major cause of secondary osteoporosis and are associated with increased fracture rate and decreased bone quality. The American College of Rheumatology guidelines for glucocorticoid-induced osteoporosis recommend bisphosphonate (BSP) treatment for most patients receiving high-dose or long-term GC therapy [Grossman JM et al. Arthritis Care Res 2010]. Drawbacks of BSPs include adverse events (AEs), poor adherence, and treatment failures, resulting in a need for other agents to prevent and treat osteoporosis. Denosumab is a fully humanized monoclonal antibody against the receptor activator of nuclear factor-kB ligand (RANKL), which is essential for the formation, function, and survival of osteoclasts. Denosumab inhibits osteoclast activity and has been shown to reduce the incidence of hip and spine fractures and to increase hip and spine bone mineral density (BMD) in postmenopausal women [Bone HG et al. J Clin Endocrinol Metab 2013; Cummings SR et al. N Engl J Med 2009]. A subgroup analysis of patients with rheumatoid arthritis (RA) receiving GCs suggested that denosumab increases spine and hip BMD and reduces bone turnover [Dore RK et al. Ann Rheum Dis 2010].

Chi Chiu Mok, MD, Tuen Mun Hospital, Hong Kong, China, reported outcomes from Denosumab in Current Users of Bisphosphonates for Glucocorticoid-Induced Osteoporosis [NCT01465568]. This 12-month, open-label, randomized trial conducted at 1 site in China assessed the effects of denosumab on BMD in adults with systemic lupus erythematosus and RA who required long-term prednisolone therapy and who had suboptimal responses to 2 years or more of BSPs. Patients had received long-term prednisolone or equivalent, defined as more than 2.5 mg daily, within 3 months of trial entry. Suboptimal response to BSP was defined as lumbar spine or hip BMD failing to increase by 2% or more, BMD remaining osteoporotic with a t score less than −2.5 or z-score less than −2.0, or development of new fragility vertebral or nonvertebral fractures during BSP treatment. Patients were randomly assigned to subcutaneous denosumab 60 mg every 6 months instead of BSPs or to continuation of BSPs; 21 patients were assigned to each treatment group, and 20 in each completed 12 months of therapy. There were no significant differences in clinical characteristics between treatment groups.

Patients receiving denosumab had a significant increase in lumbar spinal BMD, the primary endpoint, compared with the BSP group at 6 months (3.07% vs 0.56%; p=0.047) and at 12 months (3.39% vs 1.48%; p=0.026); these results were adjusted for baseline BMD, duration of disease and calcium and vitamin D use, osteoporosis risk factors, and cumulative dose of prednisolone. There were no significant differences in the secondary end point of changes in hip and femoral neck BMD at 6 and 12 months between treatment groups. No new fractures developed in any patients during the trial. Bone turnover marker assays are ongoing. Denosumab was well tolerated but was associated with increased infections. AEs are summarized in Table 1.

Although 12 months of therapy with denosumab was associated with increased lumbar spine BMD in patients receiving long-term GCs who did not respond to BSP therapy, there were no increases in hip or femoral neck BMD with denosumab. These results should be confirmed in a larger study.

• © 2014 MD Conference Express®