Background Articular bone loss is a striking feature of rheumatoid arthritis (RA). The 2nd metacarpophalangeal joint is among the most commonly affected joints in RA. Denosumab is a fully human monoclonal antibody that binds with high affinity and high specificity to RANKL, resulting in inhibition of osteoclast formation, activation and survival. Denosumab suppresses bone remodeling more than alendronate, leading to greater gains in integral and cortical volumetric bone mineral density (vBMD) in patients with post-menopausal osteoporosis. Whether this observation is applicable to patients with inflammation-induced bone loss has not been addressed before. It is of great interest to study the effect of denosumab on articular bone loss in RA patients.
Objectives The objective of this study was to compare the effects of denosumab and alendronate on vBMD and cortical and trabecular microarchitecture at the 2nd metacarpal head in RA patients with low BMD by using high-resolution peripheral quantitative computer tomography (HR-pQCT).
Methods This was a 6-month, open-label, randomized controlled trial. Forty Chinese RA females with T-scores <-1.5 were randomized into 2 groups, receiving either subcutaneous injection of denosumab 60 milligram (mg) every 6 months or oral alendronate 70mg weekly. Efficacy assessment, including bone geometry, vBMD and bone microarchitecture at the 2nd metacarpal head was performed by HR-pQCT at baseline, month 3 and month 6.
Results At 6 months, there were significant increases in the cortical area in both groups and the increase appeared to be larger in alendronate group (denosumab vs. alendronate - cortical area: 7.4% vs. 15.55%; cortical thickness: 7.32% vs. 15.37%). However, group-wise differences in changes were not significant. There was no significant difference in the change over the trabecular area in either group (0.08% and 0.16%, both p>0.05). Significant increases in integral and cortical vBMD were found in both groups and the increases were comparable (integral vBMD: 2.63% vs. 2.07%, p>0.05; cortical vBMD: 2.28% vs. 1.88%, p>0.05). There was significant increase in trabecular vBMD in denosumab group (2.67%, p<0.0005), while there was no significant increase in alendronate group (1.91%, p=0.108). Trabecular microarchitecture did not change significantly over the study period.
Conclusions During a 6-months treatment, in female RA patients with low bone mass, both denosumab and alendronate demonstrated significant and comparable effect on improving integral and cortical vBMD. However, these two treatments appeared to have differing effects on bone compartments. Denosumab produced larger increase in trabecular vBMD while alendronate produced larger increase in cortical bone, in both cortical area and cortical thickness.
Cohen SB, 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 2008;58:1299-309.
Disclosure of Interest None declared
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