TOPLINE

Adults with osteoporosis who started denosumab had a modestly lower risk of developing osteoarthritis than those who started oral bisphosphonates, but this benefit was not significant in those who switched to denosumab after being on bisphosphonates.

METHODOLOGY

• Researchers emulated a target trial using claims data from Japan collected between 2015 and 2024 to assess whether the benefits of the osteoporosis drug denosumab extended to osteoarthritis prevention in adults with osteoporosis aged 50 years or older.
• They performed two comparisons: 13,485 new denosumab users were matched with 51,629 new oral bisphosphonate users, and 4309 patients who switched from bisphosphonates to denosumab were matched with 16,546 patients who continued bisphosphonates. Most patients across both groups were around 78 years old and were women.
• Denosumab was given at a dose of 60 mg every 6 months.
• The primary outcome was the incidence of new-onset knee, hand, or hip osteoarthritis over 3 years. Secondary outcomes included joint-specific osteoarthritis (knee, hand, and hip) over 3 years.
• Researchers used both an intention-to-treat analysis, in which patients were followed up regardless of treatment changes, and a per-protocol analysis, in which only patients who stayed on their assigned treatment were included.

TAKEAWAY

• New users of denosumab had a 16% lower risk of developing osteoarthritis over 3 years than new users of oral bisphosphonates (relative risk, 0.84; 95% CI, 0.73-0.89). This pattern was observed in both the intention-to-treat and per-protocol analyses.
• Among new users, starting denosumab was associated with a lower risk for knee and hip osteoarthritis than starting oral bisphosphonates.
• The risk for osteoarthritis was relatively lower in patients who switched from bisphosphonates to denosumab than in those who stayed on bisphosphonates, although this finding was statistically nonsignificant.

IN PRACTICE

“Given the observational nature of the study and claims-based outcome ascertainment, these findings should be interpreted with caution and require further evaluation using clinically validated osteoarthritis outcomes,” the authors of the study wrote.

SOURCE

The study was led by Masaki Hatano, MD, MPH, University of Tokyo, Tokyo, Japan. It was published online on July 22, 2026, in the Journal of Bone and Mineral Research.

LIMITATIONS

The database lacked detailed data on indicators of the severity of osteoporosis. Residual or unmeasured confounding may have influenced the findings. Reliance on diagnostic codes may have underestimated osteoarthritis cases.

DISCLOSURES

The study received funding from the Ministry of Health, Labour and Welfare, Japan. One author reported receiving an institutional grant from the funding source. Another author reported having a collaborative research agreement with Amgen Inc.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.