Comparative Risk of First Hospitalized Vertebral Fracture with Denosumab Versus Zoledronic Acid: A Real-World Cohort Study

Abstract

This retrospective new-user cohort study evaluated the association between denosumab 60 mg and zoledronic acid 5 mg with first hospitalized vertebral fracture in adults aged ≥50 years receiving routine care in a Chinese hospital system. Eligible treatment initiators were identified from hospital injection and administration records at the Affiliated Kunshan Hospital of Jiangsu University between October 2021 and December 2024. Patients with a history of vertebral fracture, cancer, Paget disease, or previous alendronate use were excluded. The primary outcome was the first hospitalized vertebral fracture occurring >30 days after treatment initiation. The complete-case cohort consisted of 3,116 treatment initiators, with a total of 60 events, including 27 among patients receiving zoledronic acid and 33 among those receiving denosumab. In crude analysis, denosumab was associated with a higher fracture hazard than zoledronic acid (HR 3.02, 95% CI 1.46–6.26). In the primary overlap-weighted analysis, which estimated the average treatment effect in the overlap population, the HR was 2.05 (95% CI, 0.88–4.78). The doubly robust overlap-weighted analysis yielded an HR of 1.64 (95% CI, 0.65–4.17). All adjusted confidence intervals included the null; therefore, the adjusted analyses did not demonstrate a statistically significant difference between treatments. These findings should be interpreted with caution because of the limited number of events, treatment channeling, calendar imbalance, incomplete information on treatment persistence, and the potential for residual confounding.