Use of selective serotonin reuptake inhibitors and risk of fracture: a systematic review and meta-analysis.
Level 3 - non-randomized controlled study
Systematic review and meta-analysis of observational (cohort and case-control) studies
PubMed 22258738 · doi:10.1002/jbmr.1554
What was done
Authors conducted a systematic review and random-effects meta-analysis searching MEDLINE, EMBASE, and the Cochrane Library up to October 20, 2010. Two independent evaluators extracted data from 12 observational studies (seven case-control and five cohort studies) examining the association between selective serotonin reuptake inhibitor (SSRI) use and fracture risk. Subgroup analyses evaluated the number of adjusted risk factors, anatomical fracture site, and exposure duration.
What was found
Across 12 observational studies, SSRI use was associated with an increased risk of fracture (adjusted OR = 1.69, 95% CI 1.51–1.90, I² = 89.9%). Studies adjusting for fewer than four key variables showed larger effect sizes (adjusted OR = 1.83, 95% CI 1.57–2.13, I² = 88.0%) than those adjusting for four or more (adjusted OR = 1.38, 95% CI 1.27–1.49, I² = 46.1%). Site-specific risks were: hip/femur OR = 2.06 (95% CI 1.84–2.30, I² = 62.3%), wrist/forearm OR = 1.51 (95% CI 1.26–1.82, I² = 76.6%), and spine OR = 1.34 (95% CI 1.13–1.59, I² = 48.5%). Fracture risk was highest within 6 weeks before index date (adjusted OR = 3.83, 95% CI 1.96–7.49, I² = 41.5%) compared to 6 weeks or more (adjusted OR = 1.60, 95% CI 0.93–2.76, I² = 63.1%).
Why it matters
This review demonstrates that SSRI use is consistently associated with increased fracture risk, especially at the hip and early in the course of treatment, highlighting the need for baseline bone health and fall-risk evaluations.
Limits
All included studies were observational, leaving residual confounding by indication (e.g., depression severity or underlying physical frailty). Significant statistical heterogeneity was present across analyses (overall I² = 89.9%), and total participant count, specific drug molecules, and dosage data were not reported in the abstract.
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