Background Rheumatoid arthritis (RA), caused by upregulation of proinflammatory cytokines, is characterized by overexpression of receptor activator of nuclear factor kappa-B ligand (RANKL) in the synovial membrane, which promotes osteoclast differentiation and thus increases bone resorption. Denosumab, an antibody against RANKL, prevents RANKL/RANK interactions and inhibits osteoclast-mediated bone resorption. This study investigated whether denosumab can prevent the inflammation caused by excessive bone resorption in RA patients in comparison with bisphosphonates, which directly prevent osteoclast-mediated bone resorption.
Objectives RA patients in the Akita Orthopedic Group on Rheumatoid Arthritis (AORA) registry included 58 and 49 newly denosumab-treated and bisphosphonate-treated patients, respectively.
Methods For RA, the Steinbrocker classification was measured at pretreatment and use of glucocorticoid, methotrexate, and biological agents, DAS28-ESR, simplified disease activity index (SDAI), erythrocyte sedimentation rate, and matrix metalloproteinase 3 were measured at pre-treatment and 6 and 12 months post-treatment. For bone metabolism, bone-specific alkaline phosphatase (BAP), indicating bone formation, tartrate-resistant acid phosphatase 5b (TRACP-5b), indicating bone resorption, and bone mineral density (BMD) of the lumbar and femoral neck were measured at pre-treatment, and 6 and 12 months post-treatment.
Results For RA, the Steinbrocker class and stage were significantly higher in the denosumab group compared with the bisphosphonate group (p<0.0001 and p=0.0004, respectively). Use of biological agents was also significantly higher in the denosumab group compared with the bisphosphonate group at pre-treatment and 12 months post-treatment (p=0.006 and p=0.0467, respectively). There were no significant differences in DAS28-ESR and SDAI between the periods for denosumab or bisphosphonates (Figure). For bone metabolism, denosumab reduced BAP at 6 and 12 months post-treatment compared with pre-treatment (p=0.006 and p=0.0132, respectively) (Figure). There were no significant differences in BMD of the lumbar and femoral neck between the periods for denosumab or bisphosphonates, but denosumab revealed a tendency toward increases and bisphosphonates revealed a tendency toward decreases.
Conclusions Denosumab and bisphosphonates did not suppress RA activity, but denosumab prevented excessive bone turnover more effectively than bisphosphonates.
Cohen SB, Dore RK, Lane NE, et al. Denosumab treatment effects on structural damage, bone mineral density, and bone turnover in rheumatoid arthritis: a twelve-month, multicenter, randomized, double-blind, placebo-controlled, phase II clinical trial. Arthritis Rheum 58 (5): 1299–1309, 2008.
Acknowledgement We thank all the patients and AORA members who participated in this research.
Disclosure of Interest None declared