Abstract
Summary
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).
Introduction
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.
Methods
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.
Results
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).
Conclusions
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.
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Acknowledgements
We thank Yi-Han Sheu from Epidemiology, Harvard School of Public Health, USA, for his comments and suggestions on our abstract, and Che-Wei Su at Mackay Medical College, Taiwan, for technical support and literature collection.
Author contributions
ICMJE criteria for authorship read and met for all authors. Designed the experiments/the study: SSC, and ChienCL. Analyzed the data: SHL, WTH, ChihCL, CCC, and SSC. Collected data/did experiments for the study: SHL, WTH, AEF, and YWT. Wrote the first draft of the paper: SHL, JW, and ChihCL. Reviewed the final draft: WTH, ChihCL, AEF, CCC, and ChienCL. Developed research concept and oversaw research: SSC and ChienCL. Approved the final draft: SSC and ChienCL.
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This work is supported by research grants from Taiwan National Ministry of Science and Technology (MOST 104–2314-B-002-039-MY3) and National Taiwan University Hospital (NTUH. 105-P12). No funding bodies had any role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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Additional information
The given name and surname of the co-author A. Esmaily-Fard were transposed in the original publication; the article has now been corrected in this respect.
An erratum to this article is available at http://dx.doi.org/10.1007/s00198-017-3938-y.
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Lee, SH., Hsu, WT., Lai, CC. et al. Use of antipsychotics increases the risk of fracture: a systematic review and meta-analysis. Osteoporos Int 28, 1167–1178 (2017). https://doi.org/10.1007/s00198-016-3881-3
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DOI: https://doi.org/10.1007/s00198-016-3881-3