Denosumab May Modestly Lower risk of developing Osteoarthritis: Study
Researchers have found in a new study that adults with osteoporosis who initiated denosumab had a modestly lower risk of developing osteoarthritis compared with those starting oral bisphosphonates. However, this potential benefit was not statistically significant among patients who switched to denosumab after prior bisphosphonate therapy. The study was published in the Journal of Bone and Mineral Research by Masaki H. and colleagues.
In order to reduce immortal time bias and residual confounding, longitudinal health insurance claims data obtained during 2015 to 2024 within Japan was used for the study of osteoporotic individuals aged 50 years and above. Propensity score matching was performed based on two different target comparators; the primary comparator included new users of denosumab and oral bisphosphonate and the secondary comparator involved patients who switched from oral bisphosphonates to denosumab and those who continued oral bisphosphonates.
The overall occurrence of osteoarthritis was defined as the primary endpoint, and joint-specific occurrence of osteoarthritis in knee, hip, and hands was considered secondary endpoints within a period of 3 years. The absolute risk reduction (ARR) and relative risk (RR) estimates were calculated at 3 years using Kaplan–Meier estimators within per-protocol (PP) and intention-to-treat (ITT) analysis approach.
Key findings:
- n the per-protocol new-user comparison, denosumab initiation demonstrated a statistically significant absolute risk reduction (ARR) for incident osteoarthritis of 2.0% (95% confidence interval [CI], 1.1%–3.2%) and a relative risk (RR) of 0.83 (95% CI, 0.73–0.91) compared with oral bisphosphonates.
- In the intention-to-treat new-user framework, denosumab was similarly associated with an ARR of 1.9% (95% CI, 1.3%–3.3%) and an RR of 0.84 (95% CI, 0.73–0.89).
- In the switch-continue comparison, denosumab exhibited an attenuated ARR of 0.9% (95% CI, –0.2% to 2.8%) and an RR of 0.92 (95% CI, 0.76–1.02), which did not reach statistical significance.
- Under ITT analysis, the switch-continue cohort showed a corresponding ARR of 1.2% (95% CI, –0.2% to 2.7%) and an RR of 0.89 (95% CI, 0.77–1.02).
Conclusively, there is a reduced risk for new onset osteoarthritis in those who start using denosumab compared to oral bisphosphonates in the older population suffering from osteoporosis while the switch from bisphosphonate to denosumab results in an insignificant reduction in the same.
Reference:
Masaki Hatano, Yuya Kimura, Akira Okada, Hisatoshi Ishikura, Takeyuki Tanaka, Taku Saito, Sakae Tanaka, Hideo Yasunaga, Osteoarthritis risk associated with denosumab in adults with osteoporosis: A target trial emulation, Journal of Bone and Mineral Research, 2026;, zjag113, https://doi.org/10.1093/jbmr/zjag11
