Novel hypnotics use and hip fracture risk in middle-aged and older adults: A large, population-based cohort study in Japan.

Aim: To investigate the relationship between the prescription of novel hypnotics (melatonin receptor agonists [MRAs] and orexin receptor antagonists [ORAs]) and the risk of hip fractures in a large cohort of Japanese patients.

Methods: In this retrospective study, we analyzed data from a large health insurance claims database. Among subscribers aged ≥50 years between April 2014 and September 2021, those assigned the disease code of hip fracture were included. Each patient's prescription history for hypnotics was examined to identify the exposure and non-exposure periods. The relationship between exposure to hypnotics and the development of hip fractures was analyzed using the Mayo-updated Cox proportional hazards regression model.

Results: In total, 269,097 patients developed hip fractures. The prescription of any hypnotic was significantly associated with hip fracture incidence (adjusted hazard ratio [aHR], 2.30; 95% confidence interval [CI], 2.27-2.32). In the analysis by class of hypnotics, the hazard ratio was highest for ORAs (aHR, 3.09; 95% CI, 3.03-3.16), followed by that for MRAs (aHR, 2.45; 95% CI, 2.38-2.52).

Conclusion: Novel hypnotics use was significantly associated with the development of hip fractures, and patients prescribed ORAs and MRAs should be cautioned about the risk of hip fractures.