Zolpidem use and risk of fractures: a systematic review and meta-analysis
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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.
KeywordsFracture Hypnotics Meta-analysis Non-benzodiazepine Zolpidem
This work was supported by Wonkwang University in 2015.
SM Park and J Ryu were responsible for the initial plan, study design, data collection, data extraction, data interpretation, manuscript drafting, and conducting the study. D Shin was responsible for analyzing the data. J Lee was responsible for data extraction and critical revision of the manuscript. JM Yoon was responsible for critical revision of the manuscript for important intellectual content. DR Lee was responsible for the initial plan, study design, data interpretation, manuscript drafting, supervision, and critical revision of the manuscript for important intellectual content. The content of this manuscript is solely the responsibility of the authors. DR Lee is the guarantor for this manuscript and has full responsibility for this study.
Compliance with ethical standards
Conflict of interest
Sang Min Park, Jihye Ryu, Dong Ryul Lee, Doosup Shin, Jae Moon Yun, and Jungun Lee declare that they have no conflicts of interest.
- 20.Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D, Moher D, Becker BJ, Sipe TA, Thacker SB (2000) Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA 283:2008–2012CrossRefPubMedGoogle Scholar
- 24.Wells GA, Shea BO, Connell D, Peterson J, Welch V, Losos M, et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality if nonrandomized studies in meta-analyses. http://www.ohri.ca/programs/clinical_epidemiology/oxford.htm Accessed 19 Sep 2015
- 32.Cappelle S, Ramon I, Dekelver C, Paesmans M, Moreau M, Bergmann P, Karmali R, Peretz A, Rozenberg S, Body JJ (2013) Distribution of clinical risk factors for fracture in a brussels cohort: an interim-analysis of the frisbee study. Osteoporos Int 24:S176Google Scholar
- 33.Chung CH (2014) The insomnia treatment, drug usage and their side effects in Taiwan: analysis of 2009-2011 Nationwide Health Insurance Database. Pharmacoepidemiol Drug Saf 23:S88–89Google Scholar