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.
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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
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Acknowledgments
We thank Kay E. Wellik for her consultation on literature search.
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Appendix
Appendix
Search strategy for MEDLINE (OVID)
001 exp Serotonin Uptake Inhibitors/
002 serotonin uptake inhibitor#.mp.
003 exp Antidepressive Agents/
004 antidepressant#.mp.
005 exp Fluoxetine/or fluoxetine.mp.
006 ssri#.mp.
007 fluvoxamine.mp. or exp Fluvoxamine/
008 sertraline.mp. or exp Sertraline/
009 citalopram.mp. or Citalopram/
010 escitalopram.mp. or exp Citalopram/
011 paroxetine.mp. or exp Paroxetine/
012 1 or 2 or 3 or 4 or 5 or 6 or 7 or 8 or 9 or 10 or 11
013 exp Fractures, Bone/
014 fracture#.mp.
015 exp Osteoporosis/or osteoporosis.mp.
016 osteopenia.mp. or exp Bone Diseases, Metabolic/
017 bone mineral density.mp. or exp Bone Density/
018 bone density.mp.
019 bone loss.mp.
020 bone#.mp.
021 13 or 14 or 15 or 16 or 17 or 18 or 19 or 20
022 12 and 21
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Wu, Q., Bencaz, A.F., Hentz, J.G. et al. Selective serotonin reuptake inhibitor treatment and risk of fractures: a meta-analysis of cohort and case–control studies. Osteoporos Int 23, 365–375 (2012). https://doi.org/10.1007/s00198-011-1778-8
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DOI: https://doi.org/10.1007/s00198-011-1778-8