The association of melatonin use and hip fracture: a matched cohort study

Summary By using propensity-score matched cohorts, we compared the risk of incident hip fracture between melatonin initiators and hypnotic benzodiazepines initiators. The initiation of melatonin was not associated with an increased risk of hip fracture. Introduction Melatonin is hypothesized to suppress bone loss, but a previous study reported an increased risk of hip fracture among melatonin users compared with non-users, which was however susceptible to confounding by indication. This study aimed to compare the risk of hip fracture between melatonin initiators and initiators of its active comparators, i.e., hypnotic benzodiazepines. Methods Among individuals aged 40 years or older without a history of hip fracture or cancer in the IQVIA Medical Research Database (IMRD) in the UK (2000–2018), a propensity score-matched cohort study was conducted to examine the association of melatonin initiation vs. hypnotic benzodiazepines initiation with the risk of hip fracture. Results After propensity score matching, 9,038 patients were included (4,519 melatonin initiators and 4,519 hypnotic benzodiazepines initiators). During the entire follow-up, 41 cases of hip fracture occurred in the melatonin cohort, and 51 cases occurred in the hypnotic benzodiazepines cohort. The absolute rate difference in hip fracture between melatonin initiators and hypnotic benzodiazepines initiators was -0.8 (95% CI: -1.9 to 0.3) per 1000 person-years and the multivariable-adjusted hazard ratio (HR) of hip fracture for melatonin initiators was 0.78 (95% CI: 0.51 to 1.17). Conclusion In this population-based cohort study, the risk of hip fracture among melatonin initiators was not higher, if not lower, than that among hypnotic benzodiazepines initiators.