Denosumab’s bone density edge may not translate to fewer fractures

Clinical takeaway: Continue to individualize the choice between denosumab and alendronate for postmenopausal women with rheumatoid arthritis taking long-term glucocorticoids. This small observational study does not provide enough fracture evidence to favor either agent.

Postmenopausal women with rheumatoid arthritis (RA) who take long-term glucocorticoids face overlapping risks for osteoporosis and fragility fractures. Both denosumab and alendronate are used to reduce that risk, but direct comparisons in this particularly vulnerable population are limited.

Researchers reviewed records from 295 women with RA and osteoporosis treated at multiple centers in China between 2018 and 2023. After matching patients on 22 baseline factors, the analysis included 124 women receiving denosumab 60 mg every six months or alendronate 70 mg weekly.

After one year, denosumab produced a statistically greater increase in lumbar spine bone mineral density than alendronate, but the between-group difference was only 0.444%. The authors noted that this was well below the roughly 3% change generally considered clinically meaningful for fracture reduction. No significant differences were found at the total hip or femoral neck or in bone-turnover markers or RA disease activity.

Fragility fractures occurred in five denosumab-treated patients and one alendronate-treated patient, corresponding to rates of 8.1% and 1.6%, respectively. The difference was not statistically significant, and the wide confidence interval and six total events make it impossible to determine whether fracture risk truly differed. Vertebral fractures also were not systematically screened, and the retrospective design cannot exclude differences that influenced treatment choice or fracture risk.

The findings underscore that improvements in bone mineral density do not necessarily predict fracture protection, particularly in patients with RA who remain exposed to glucocorticoids and chronic inflammation. This study does not establish that denosumab increases fracture risk or that alendronate is the preferred treatment.

“Available evidence does not favor one agent over the other in this context,” the authors concluded.

Source: Chen M, et al. (2026 Aug 17) Ther Adv Musculoskelet Dis. 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