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although melatonin prescribing in England has been increasing in recent years, there have been no large scale studies on the safety of melatonin compared to other medical treatments for insomnia. The primary aim of this study was to examine the association between exposure to melatonin, hypnotic benzodiazepines (temazepam, nitrazepam) or Z-drugs (zolpidem, zopiclone) and fracture risk.retrospective cohort study.309 general practices contributing to The Health Improvement Network (THIN) between 2008 and 2013.1,377 patients aged 45 years and older prescribed melatonin; 880 patients prescribed hypnotic benzodiazepines; 1,148 patients prescribed Z-drugs and 2,752 unexposed controls matched by age, gender and practice.fracture following prescription of study drugs ascertained from practice records.the unadjusted hazard ratios for fracture during the follow-up period were 1.90 (95% CI 1.41–2.57) for melatonin, 1.70 (95% CI 1.18–2.46) for hypnotic benzodiazepines and 2.03 (95% CI 1.45–2.84) for Z-drugs. After adjustment for 26 covariates, the hazard ratios were 1.44 (95% CI 1.01–2.04) for melatonin, 1.26 (95% CI 0.82–1.92) for hypnotic benzodiazepines and 1.52 (95% CI 1.04–2.23) for Z-drugs. Only patients with three or more melatonin prescriptions had elevated risk. The mean time to fracture was 1.04 years and there was no significant difference in mean time to fracture between the cohorts.in this large cohort of patients attending UK primary care, prescriptions for melatonin and Z-drugs were associated with a significantly increased risk of fracture. With the use of melatonin increasing steadily overtime, this study adds to the literature on the safety profile of this drug.