OBJECTIVES: The safety and efficacy of anti-osteoporosis medications (AOMs) are well established. However, the optimal timing of initiating AOMs remains questioned. This study aimed to investigate the association between different initial time of AOMs and the risk of subsequent fracture-related hospitalization and mortality in patients with hip fracture.METHODS: Using Taiwan’s National Health Insurance Research Database, we identified patients newly diagnosed with hip fracture and initiated AOMs (including bisphosphonates, calcitonin, raloxifene, and denosumab) within one year post index hip fracture. We further categorized AOMs users according to their initial date of first AOMs prescription as ultra-early, early, late and ultra-late users, defined as those who initiate AOMs within 14 days, 15-84 days, 85-252days and later than 252 days post index hip fracture, respectively. Multivariable Cox proportional hazard models were performed to estimate the association between different initial date of AOMs and the risk of subsequent fracture-related hospitalization and mortality.RESULTS: We identified 75,480 patients newly diagnosed hip fracture between 2009 and 2012. Among them, only 11,027 patients received AOMs within 1year post index hip fracture. There are 1554, 6578, 2266, 629 patients in the ultra-early, early, late, ultra-late group, respectively. Compared to early user, ultra-early and ultra-late users were associated with significant higher risks of subsequent fracture-related hospitalization [adjusted hazard ratio (aHR): 1.22 (95% confidence interval (CI) 1.00-1.47; aHR:1.50, 95% CI 1.09-2.04, respectively]. Particularly, ultra-late users were also associated with a significant higher risk of mortality (aHR: 1.81, 95% CI 1.49-2.02).CONCLUSIONS: Extremely late use of AOMs was associated with the risk of subsequent fracture-related hospitalization and mortality.