Association between denosumab use and risk of osteoarthritis among adults with osteoporosis in a real-world cohort

Objective: To estimate the effect of denosumab compared with bisphosphonates on reducing the risk of knee or hip osteoarthritis (OA) among adults with osteoporosis in a real-world cohort. Method: This new-user, active-comparator retrospective real-world cohort utilized electronic health records from the TriNetX Network. Participants diagnosed with osteoporosis between January 1, 2014 and December 31, 2023 were selected. We used propensity-score matching (PSM) to balance potential confounders between denosumab users and bisphosphonate users. Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of incident knee and hip OA by comparing PSM groups. Results: 59,157 new users of denosumab were matched on propensity score to 59,157 participants of bisphosphonate users (mean age 70 years; 87% female). The 10-year incidence probability of knee and hip OA in denosumab users was 19.2% (4839 events and 14.5% (3396 events), while in bisphosphonate users it was 21.4% (5389 events) and 14.4% (3388 events). Compared with bisphosphonate, denosumab users were significantly associated with a reduced risk of any OA (HR 0.96, 95% CI 0.94–0.98), knee OA (HR, 0.87, 95% CI, 0.84–0.91), but not with hip OA (HR, 0.98, 95% CI, 0.94–1.03), or thumb carpometacarpal OA (HR 0.94, 95% CI 0.87–1.01). These associations were more pronounced among older participants (≥ 65 years, HR 0.88, 95% CI 0.84–0.91 for knee OA), females (HR 0.87, 95% CI 0.83–0.91 for knee OA), and individuals of Asian ethnicity (HR 0.73, 95% CI 0.63–0.84 for knee OA). Conclusions: Denosumab use was associated with a reduced risk of incident knee OA compared with bisphosphonates in adults with osteoporosis, with the association being more pronounced among older adults, females, and individuals of Asian ethnicity. This study suggests that denosumab could attenuate the development of knee OA, warranting further clinical trials.