Osteoporosis International

, Volume 23, Issue 1, pp 365–375 | Cite as

Selective serotonin reuptake inhibitor treatment and risk of fractures: a meta-analysis of cohort and case–control studies

  • Q. Wu
  • A. F. Bencaz
  • J. G. Hentz
  • M. D. Crowell
Original Article

Abstract

Summary

Studies on use of selective serotonin reuptake inhibitors (SSRIs) and risk of fracture have yielded inconsistent results. This meta-analysis, which pooled results from 13 qualifying cohort and case–control studies, found that SSRIs were associated with a significantly increased risk of fractures.

Introduction

This study was conducted to assess whether people who take SSRIs are at an increased risk of fracture.

Methods

We conducted a meta-analysis of observational studies. Relevant studies published by February 2010 were identified through literature searches using MEDLINE (from 1966), EMBASE (from 1988), PsycINFO (from 1806), and manual searching of reference lists. Only cohort or case–control studies that examined the association of SSRIs and risk of fracture and bone loss were included. Data were abstracted independently by two investigators using a standardized protocol; disagreements were resolved by consensus. Random effects models were used for pooled analysis due to heterogeneity in the studies.

Results

Thirteen studies met inclusion criteria. Overall, SSRI use was associated with a significantly increased risk of fracture (relative risk, RR, 1.72; 95% CI [1.51, 1.95]; P < 0.001). An increased fracture risk associated with SSRIs also was observed in the three studies that adjusted for bone mineral density (RR, 1.70; 95% CI [1.28, 2.25]; P < 0.001) and in the four studies that adjusted for depression (RR 1.74; 95% CI [1.28, 2.36]; P < 0.001). SSRI use was not associated with bone loss in the two cohort studies of women (P = 0.29). The overall association between SSRI use and fracture risk was weaker (RR, 1.40; 95% CI [1.22, 1.61]), though still significant (P < 0.001) in analyses that accounted for apparent publication bias.

Conclusions

Use of SSRIs is associated with increased risk of fracture. The SSRIs may exert an increased risk of fracture independent of depression and bone mineral density.

Keywords

Antidepressant Bone fractures Bone mineral density Depression Osteoporosis Serotonin reuptake inhibitors 

Abbreviations

BMD

Bone mineral density

CI

Confidence interval

HR

Hazard ratio

MOOSE

Meta-analysis of Observational Studies in Epidemiology

OR

Odds ratio

PRISMA

Preferred Reporting Items for Systematic Reviews and Meta-analyses

RR

Relative risk

SSRI

Selective serotonin reuptake inhibitor

Notes

Acknowledgments

We thank Kay E. Wellik for her consultation on literature search.

Conflicts of interest

None.

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Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2011

Authors and Affiliations

  • Q. Wu
    • 1
  • A. F. Bencaz
    • 2
  • J. G. Hentz
    • 1
  • M. D. Crowell
    • 1
  1. 1.College of MedicineMayo ClinicScottsdaleUSA
  2. 2.School of MedicineLouisiana State University Health Sciences CenterNew OrleansUSA

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