Zolpidem use and risk of fractures: a systematic review and meta-analysis.

Journal Article (Systematic Review;Review;Journal Article)


Zolpidem is a representative of non-benzodiazepine hypnotics. Recent epidemiologic studies have reported increased fracture risk in patients taking zolpidem, but the results have been inconsistent. The present meta-analysis shows that the use of zolpidem is associated with an increased risk of fractures.


Previous studies have reported inconsistent findings regarding the association between the use of zolpidem and the risk of fractures. We performed a systematic literature review and meta-analysis to assess the association.


We identified relevant studies by searching MEDLINE, EMBASE, Cochrane Library, and PsycINFO without language restrictions (until August 2014). Methodological quality was assessed based on the Newcastle-Ottawa Scale (NOS).


A total of 1,092,925 participants (129,148 fracture cases) were included from 9 studies (4 cohort, 4 case-control, and 1 case-crossover study). Overall, the use of zolpidem was associated with an increased risk of fracture (relative risk [RR] 1.92, 95 % CI 1.65-2.24; I (2) = 50.9 %). High-quality subgroups (cohort studies, high NOS score, adjusted for any confounder, or adjusted for osteoporosis) had higher RRs than the corresponding low-quality subgroups (high quality, 1.94-2.76; low quality, 1.55-1.79). Of note, the risk for hip fracture was higher than that for fracture at any site (hip fracture, RR 2.80, 95 % CI 2.19-3.58; fracture at any site, RR 1.84, 95 % CI 1.67-2.03; P < 0.001).


The use of zolpidem may increase the risk of fractures. Clinicians should be cautious when prescribing zolpidem for patients at high risk of fracture.

Full Text

Duke Authors

Cited Authors

  • Park, SM; Ryu, J; Lee, DR; Shin, D; Yun, JM; Lee, J

Published Date

  • October 2016

Published In

Volume / Issue

  • 27 / 10

Start / End Page

  • 2935 - 2944

PubMed ID

  • 27105645

Electronic International Standard Serial Number (EISSN)

  • 1433-2965

International Standard Serial Number (ISSN)

  • 0937-941X

Digital Object Identifier (DOI)

  • 10.1007/s00198-016-3605-8


  • eng