Zolpidem use and risk of fractures: a systematic review and meta-analysis.
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.
Department of Family Medicine, Seoul National University Hospital, 103, Daehak-ro, Jongno-gu, 03080, Seoul, Republic of Korea.|Department of Education and Research, Seoul National University Hospital, 103, Daehak-ro, Jongno-gu, 03080, Seoul, Republic of Korea.
S M
SM
Park
Department of Family Medicine, Seoul National University Hospital, 103, Daehak-ro, Jongno-gu, 03080, Seoul, Republic of Korea.
J
J
Ryu
Department of Family Medicine, Wonkwang University Sanbon Hospital, Wonkwang University School of Medicine, 321, Sanbon-ro, Gunpo-si, 15865, Gyeonggi-do, Republic of Korea. rednose7695@gmail.com.
D R
DR
Lee
Department of Biomedical Sciences, Seoul National University College of Medicine, 101, Daihak-ro, Jongno-gu, 03080, Seoul, Republic of Korea.
D
D
Shin
Department of Family Medicine, Seoul National University Hospital, 103, Daehak-ro, Jongno-gu, 03080, Seoul, Republic of Korea.
J M
JM
Yun
Department of Family Medicine, Wonkwang University Sanbon Hospital, Wonkwang University School of Medicine, 321, Sanbon-ro, Gunpo-si, 15865, Gyeonggi-do, Republic of Korea.
J
J
Lee
D050723:Fractures, Bone / Q000453:epidemiology*; D006801:Humans; D011725:Pyridines / Q000009:adverse effects*; D012306:Risk; D000077334:Zolpidem
D011725:Pyridines; D000077334:Zolpidem
Fracture; Hypnotics; Meta-analysis; Non-benzodiazepine; Zolpidem