Osteoporosis International

, Volume 27, Issue 10, pp 2935–2944 | Cite as

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

  • S. M. Park
  • J. Ryu
  • D. R. LeeEmail author
  • D. Shin
  • J. M. Yun
  • J. Lee
Original 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.


Fracture Hypnotics Meta-analysis Non-benzodiazepine Zolpidem 



This work was supported by Wonkwang University in 2015.

Author contributions

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.


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Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2016

Authors and Affiliations

  • S. M. Park
    • 1
    • 2
  • J. Ryu
    • 1
  • D. R. Lee
    • 3
    Email author
  • D. Shin
    • 4
  • J. M. Yun
    • 1
  • J. Lee
    • 3
  1. 1.Department of Family MedicineSeoul National University HospitalSeoulRepublic of Korea
  2. 2.Department of Education and ResearchSeoul National University HospitalSeoulRepublic of Korea
  3. 3.Department of Family MedicineWonkwang University Sanbon Hospital, Wonkwang University School of MedicineGunpo-siRepublic of Korea
  4. 4.Department of Biomedical SciencesSeoul National University College of MedicineSeoulRepublic of Korea

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