Osteoporosis International

, Volume 23, Issue 1, pp 365–375

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



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.


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


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.


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.


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.


Antidepressant Bone fractures Bone mineral density Depression Osteoporosis Serotonin reuptake inhibitors 



Bone mineral density


Confidence interval


Hazard ratio


Meta-analysis of Observational Studies in Epidemiology


Odds ratio


Preferred Reporting Items for Systematic Reviews and Meta-analyses


Relative risk


Selective serotonin reuptake inhibitor

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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