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.

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.

DESIGN

Retrospective multi-center propensity score-matched cohort study.

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.