Objective  To investigate the effectiveness of denosumab in reducing fracture risk among patients with osteoporosis in real-world clinical practice, and to compare the differences in fracture risk between patients who sustained denosumab treatment and those who discontinued treatment after a single dose.

Methods  The retrospective cohort study was employed. The patients diagnosed with osteoporosis who initiated denosumab from January 2019 to October 2024 were collected, and the patients were categorized into a continuous treatment group and a single-dose discontinued group based on whether they received a second denosumab injection within 180 days of the initial dose, with a 45-day grace period. Propensity score matching was used to balance the baseline characteristics between the two groups. The primary outcome was composite fractures, and secondary outcomes included hip fractures, vertebral fractures, and non-hip non-vertebral fractures. Kaplan–Meier curves were used to estimate survival curves, and Cox proportional hazards models were applied to adjust for residual imbalances in covariates and estimate hazard ratios (HR) with 95% confidence intervals (CI).

Results  A total of 12,010 patients were included, of whom 3,134 continued denosumab treatment and 8,876 were in the single-dose dis-continuation group. Compared with the single-dose discontinuation group, patients in the continuous treatment group had a significantly reduced risk of developing composite fractures [HR=0.61, 95%CI (0.52, 0.72), P<0.001], hip fractures [HR=0.30, 95%CI (0.19, 0.47), P<0.001], vertebral fractures [HR=0.69, 95%CI (0.55, 0.85), P<0.001], and non-hip non-vertebral fractures [HR=0.51, 95%CI (0.40, 0.65), P<0.001].

Conclusion  In real-world clinical practice in China, continuous treatment with denosumab was associated with a significant reduction in fracture risk among patients with osteoporosis. These findings highlight the importance of maintaining treatment persistence in newly treated patients to prevent rebound fractures after discontinuation.

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