title: Use of antipsychotics increases the risk of fracture: a systematic review and meta-analysis.
abstract: Our systematic review and meta-analysis of observational studies indicated that the use of antipsychotics was associated with a nearly 1.5-fold increase in the risk of fracture. First-generation antipsychotics (FGAs) appeared to carry a higher risk of fracture than second-generation antipsychotics (SGAs).
  
  
  
  The risk of fractures associated with the use of antipsychotic medications has inconsistent evidence between different drug classes. A systematic review and meta-analysis was conducted to evaluate whether there is an association between the use of antipsychotic drugs and fractures.
  
  
  
  Searches were conducted through the PubMed and EMBASE databases to identify observational studies that had reported a quantitative estimate of the association between use of antipsychotics and fractures. The summary risk was derived from random effects meta-analysis.
  
  
  
  The search yielded 19 observational studies (n = 544,811 participants) with 80,835 fracture cases. Compared with nonuse, use of FGAs was associated with a significantly higher risk for hip fractures (OR 1.67, 95% CI, 1.45-1.93), and use of second generation antipsychotics (SGAs) was associated with an attenuated but still significant risk for hip fractures (OR 1.33, 95% CI, 1.11-1.58). The risk of fractures associated with individual classes of antipsychotic users was heterogeneous, and odds ratios ranged from 1.24 to 2.01. Chlorpromazine was associated with the highest risk (OR 2.01, 95% CI 1.43-2.83), while Risperidone was associated with the lowest risk of fracture (OR 1.24, 95% CI 0.95-1.83).
  
  
  
  FGA users were at a higher risk of hip fracture than SGA users. Both FGAs and SGAs were associated with an increased risk of fractures, especially among the older population. Therefore, the benefit of the off-label use of antipsychotics in elderly patients should be weighed against any risks for fracture.
authors.affiliation: Department of Rehabilitation and Physical Medicine, Taipei Veteran General Hospital, Taipei, Taiwan.|Department of Medicine, College of Medicine, National Yang Ming University, Taipei, Taiwan.
authors.forename: S-H
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Health Economics and Outcome Research Group, Department of Emergency Medicine, National Taiwan University Hospital, No.7, Chung Shan S. Rd., Zhongzheng Dist., Taipei City, 100, Taiwan.
authors.forename: W-T
authors.initials: WT
authors.lastname: Hsu
authors.affiliation: Department of Intensive Care Medicine, Chi Mei Medical Center, Liouying, Tainan, Taiwan.
authors.forename: C-C
authors.initials: CC
authors.lastname: Lai
authors.affiliation: The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: A
authors.initials: A
authors.lastname: Esmaily-Fard
authors.affiliation: Department of Family Medicine, Chang Gung Memorial Hospital, University College of Medicine, Taoyuan, Taiwan.
authors.forename: Y-W
authors.initials: YW
authors.lastname: Tsai
authors.affiliation: Department of Rehabilitation and Physical Medicine, Taipei Veteran General Hospital, Taipei, Taiwan.
authors.forename: C-C
authors.initials: CC
authors.lastname: Chiu
authors.affiliation: University of Nevada School of Medicine, Las Vegas, Nevada, USA.
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Family Medicine, Chang Gung Memorial Hospital, No.5. Fu-Hsing street, Kuei Shan Hsiang, Taoyuan, Hsien, Taiwan. sschang0529@gmail.com.|Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan. sschang0529@gmail.com.
authors.forename: S-S
authors.initials: SS
authors.lastname: Chang
authors.affiliation: Health Economics and Outcome Research Group, Department of Emergency Medicine, National Taiwan University Hospital, No.7, Chung Shan S. Rd., Zhongzheng Dist., Taipei City, 100, Taiwan. cclee100@gmail.com.
authors.forename: C C
authors.initials: CC
authors.lastname: Lee
mesh_terms: D014150:Antipsychotic Agents / Q000009:adverse effects*; D005264:Femoral Fractures / Q000139:chemically induced; D006620:Hip Fractures / Q000139:chemically induced; D006801:Humans; D058866:Osteoporotic Fractures / Q000139:chemically induced*; D018570:Risk Assessment / Q000379:methods
chemical_list: D014150:Antipsychotic Agents
keywords: Antipsychotics; Atypical antipsychotics; Conventional antipsychotics; Femur fracture; First-generation antipsychotics; Fracture; Hip fracture; Second-generation antipsychotics