Use of short-acting and long-acting hypnotics and the risk of fracture: a critical analysis of associations in a nationwide cohort

Summary - Numerous observational studies suggest that hypnotics increase the risk of fractures, and long-acting hypnotics are suggested to be especially harmful. This study showed that the highest risk of fracture was found before start of treatment and remained after end of therapy, suggesting that the increased risk during treatment is influenced by other factors, such as underlying disease. Introduction - The purpose of this study was to evaluate associations between the use of short-acting and long-acting hypnotics and the risk of fracture. Methods - Four cohorts were formed from all individuals living in Sweden aged ≥ 50 years in 2005 (n = 3,341,706). In the first cohort, individuals prescribed long-acting propiomazine (n = 233,609) were matched 1:1 with controls. In the second cohort, individuals prescribed short-acting z-drugs (zopiclone, zolpidem, and zaleplon, n = 591,136) were matched 1:1 with controls. The third and fourth cohorts consisted of full sibling pairs with discordant propiomazine (n = 83,594) and z-drug (n = 153,314) use, respectively. Results - The risk of fracture was greatest among users of hypnotics in the 90 days before the initiation of treatment, both for propiomazine (odds ratio [OR], 2.52; 95% confidence interval [CI], 2.28–2.79) and z-drugs (OR, 4.10; 95% CI, 3.86–4.35) compared with that in matched controls. Furthermore, this risk was significantly reduced after the initiation of treatment with propiomazine (OR, 1.42; 95% CI, 1.27–1.60) and z-drugs (OR, 1.67; 95% CI, 1.56–1.80) and remained the first year following the last prescribed dose both for propiomazine (OR, 1.28, 95% CI, 1.21–1.36) and z-drugs (OR, 1.19, 95% CI, 1.16–1.23). The pattern was similar in the sibling cohorts, with the greatest risk of fracture seen in the 90 days before treatment with hypnotics was initiated. Conclusion - The use of short-acting and long-acting hypnotics is associated with an increased risk of fracture. This risk was highest before initiation of treatment and remained after end of therapy. The results suggest that the increased risk during treatment is influenced by other factors such as underlying disease