Oral bisphosphonates and risk of incident osteoarthritis in individuals with osteoporosis: a target trial emulation.

OBJECTIVES

Owing to the underrepresentation of early-stage disease in randomised trials and inconsistent clinical evidence, using oral bisphosphonates to prevent incident osteoarthritis in adults with osteoporosis lacks consensus. We aimed to analyse the causal relationship between oral bisphosphonates and osteoarthritis.

METHODS

We performed a sequential nested target trial emulation with propensity score matching using longitudinal health insurance claims data from Japan collected between 2015 and 2024. Eligible individuals were aged ≥50 years with osteoporosis who had been receiving vitamin D therapy. We compared those who initiated oral bisphosphonates with those who did not initiate and continued vitamin D therapy. The primary outcome was incident osteoarthritis. Secondary outcomes included joint-specific osteoarthritis (knee, hip and hand) over a 3-year follow-up period. The absolute risk reduction (ARR) and relative risk (RR) at 3 years were estimated using a Kaplan-Meier estimator.

RESULTS

We included 10 844 bisphosphonate initiators and 21 283 non-initiators. The ARR for incident osteoarthritis was 0.4% (95% CI -1.3% to 1.0%), with an RR of 0.97 (95% CI 0.92 to 1.12). In joint-specific analyses, the ARR (95% CI) and RR (95% CI) were 0.5% (-1.1% to 1.0%) and 0.95 (0.90 to 1.12) for knee osteoarthritis; 0.2% (-0.4% to 0.7%) and 0.89 (0.64 to 1.27) for hip osteoarthritis; and -0.3% (-0.7% to 0.3%) and 1.20 (0.81 to 1.50) for hand osteoarthritis, respectively.

CONCLUSION

Oral bisphosphonate use was not associated with a lower risk of incident osteoarthritis among adults with osteoporosis.