Hip Fracture Incidence Not Higher With Use of Melatonin vs Hypnotic Benzodiazepines

Compared with hypnotic benzodiazepines, the use of melatonin is not associated with an increased risk for hip fracture incidence, according to results of a matched cohort study published in Osteoporosis International.

Recent research has highlighted the role of melatonin in maintaining functional bone metabolism, both by fostering bone formation and suppressing bone loss. However, the role of melatonin in preventing bone fracture is unclear.

Using the IQVIA Medical Research Database (IMRD), researchers in the UK analyzed the relationship between melatonin use and incidence of hip fracture from 2000 to 2018. Patients who used melatonin were propensity-score matched with those who used hypnotic benzodiazepines to avoid the risk of confounding.

Kaplain-Meier survival curves were used to calculate hip fracture incidence rates. Absolute rate difference (RD) was estimated between the melatonin and hypnotic benzodiazepine cohorts, with hazard ratios (HR) calculated using Cox proportional models.

A total of 9038 patients were included in the study, with both the melatonin and hypnotic benzodiazepine groups including 4519 participants each. The mean age of participants in the melatonin and hypnotic benzodiazepine groups was 61.6 years and 61.8 years, respectively. The length of prescription treatment for the groups was 182 and 148 days, respectively.

Hip fracture incidence was lower among the melatonin vs hypnotic benzodiazepine cohort, with 41 cases compared with 51 cases of fracture per 1000 person-years, respectively. Hip fracture rate difference between the 2 groups was -0.8 (95% CI, -1.9 to 0.3) per 1000 person-years. The hip fracture incidence HR for the melatonin cohort was 0.78 (95% CI, 0.51-1.17). Although the overall risk for hip fracture was slightly lower among melatonin vs hypnotic benzodiazepine users, these data were not statistically significant.

This study was limited by potential confounding from the lack of data on bone density and frailty parameters. In addition, the IMRD did not include data on over-the-counter medication use.

“More studies are needed to further confirm the association between melatonin use and the risk [for] hip fracture and to elaborate the underlying biologic mechanism,” the researchers noted.