Comparison of the effects of denosumab and alendronate on fracture risk and bone metabolism in postmenopausal rheumatoid arthritis patients treated with oral glucocorticoids: A propensity score-matched retrospective cohort study.
Mengmeng Chen, Lan Lu, Yujiang Mao, Lina Ji, Jianyi Xu, Junjun Chen, Yong Zhu, Jiandi Yuan, Lei Chen, Jinsheng Yu, Qiyuan Lu
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Abstract
Background: Postmenopausal rheumatoid arthritis (RA) patients receiving oral glucocorticoids (GCs) are at markedly increased risk for osteoporosis and fractures. Direct comparisons between denosumab and alendronate in this high-risk subgroup remain limited.
Objectives: To evaluate denosumab versus alendronate regarding one-year incidence of fragility fractures, bone mineral density (BMD) changes, bone turnover markers, and disease activity in postmenopausal RA patients on long-term oral GCs.
Methods: From January 2018 to December 2023, 295 patients (122 denosumab, 173 alendronate) were enrolled. Propensity score matching (1:1) balanced 22 baseline covariates, yielding 124 patients (62 per arm). Outcomes included new fragility fractures, BMD alterations (including areal BMD (aBMD)), serum procollagen type I N-terminal propeptide (P1NP) and C-terminal telopeptide of type I collagen (CTx) levels, and disease activity scores over one year.
Results: Denosumab produced a significantly greater lumbar spine aBMD gain than alendronate (between-group difference: 0.444%, P=0.025). The absolute risk difference for fragility fracture with denosumab versus alendronate was 3.2% (95% CI: -2.2% to 8.6%), corresponding to fracture rates of 8.1% vs. 1.6% (OR=5.35, 95% CI: 0.59-48.68, P=0.135). Sensitivity analyses suggested a potential trend of elevated risk, but the very low number of fracture events (n=6) precludes definitive conclusions. No significant differences were observed for other BMD sites, bone turnover markers, or disease activity.
Conclusion: In postmenopausal RA patients on GCs, denosumab was superior to alendronate for lumbar spine BMD gains. The absolute risk difference for fragility fracture with denosumab versus alendronate was 3.2% (95% CI: -2.2% to 8.6%), but this finding remains inconclusive due to insufficient power and rare events. Larger prospective studies are needed to clarify fracture outcomes.
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