Comparative outcomes of denosumab and zoledronic acid discontinuation in hip fracture surgery: a nationwide database study

Abstract

In hip fracture patients with poor medication adherence, DMAB discontinuation significantly increased the risk of subsequent vertebral and rib fractures. Additionally, higher CCI scores were associated with an increased risk of these fractures. These findings underscore the importance of maintaining treatment adherence to minimize fracture risk in this vulnerable population.

Purpose: To assess the risk of major osteoporotic fractures and periprosthetic fractures in hip fracture patients who discontinued denosumab (DMAB) or zoledronic acid (ZOL).

Methods: Data from the South Korean National Health Insurance Review and Assessment Service were analyzed, focusing on patients aged ≥ 60 years who underwent hip fracture surgery and initiated DMAB or ZOL treatment. Among 20,180 patients, 1737 discontinued DMAB, and 3720 discontinued ZOL. After 1:1 propensity score matching, 3240 patients were included in the final analysis. The DMAB group was stratified into three subgroups based on the cumulative DMAB duration after hip fracture surgery: 1-2, 2-3, and > 3 Y. Discontinuation was defined as a 270-day gap for DMAB or 540-day gap for ZOL last injections. Subsequent osteoporotic fractures after discontinuation were evaluated.

Results: DMAB discontinuation significantly increased the risk of subsequent vertebral fractures (hazard ratio [HR] = 1.81; 95% confidence interval [CI], 1.28-2.56, P = 0.01) and rib fractures (HR = 2.04; 95% CI, 1.27-3.23, P = 0.004) compared to ZOL discontinuation. Higher Charlson Comorbidity Index (CCI) scores were also significantly associated with an increased risk of subsequent vertebral (HR 1.05, 95% CI 1.03-1.09, P = 0.02) and rib fractures (HR 1.12, 95% CI 1.06-1.19, P < 0.01). Although the incidence of hip fractures was lower in DMAB discontinuation group (1 case) than in the ZOL discontinuation group (10 cases), this difference did not reach statistical significance. No significant difference was observed in the risk of other nonvertebral fractures (humerus, wrist, ankle) and periprosthetic fracture between the two groups.

Conclusion: This nationwide study, the first to use real-world data, highlighted the significant increase in the risk of vertebral and rib fracture associated with DMAB discontinuation in patients with poor adherence and higher comorbidity burden. Optimizing medication adherence is crucial to minimize the fracture risk in this vulnerable population.

Level of evidence: Level III, Prognostic.

Keywords: Anti-osteoporotic medications; Denosumab discontinuation; Hip fractures; Nationwide cohort study; Osteoporotic fractures.