Alliance between selective serotonin reuptake inhibitors and fracture risk: an updated systematic review and meta-analysis.
Level 3 - non-randomized controlled study
Systematic review and meta-analysis of observational cohort and case-control studies
PubMed 32556910 · doi:10.1007/s00228-020-02893-1
What was done
The authors conducted a systematic review and meta-analysis of observational studies identified through PubMed, Cochrane Library, and Google Scholar from inception to April 2019 to evaluate the association between selective serotonin reuptake inhibitor (SSRI) use and fracture risk in adults. Screening, data extraction, and risk of bias assessment were conducted independently by two authors.
What was found
Thirty-seven studies (14 case-control and 23 cohort studies) were included from 69 assessed. SSRIs were significantly associated with an increased fracture risk overall, with a relative risk of 1.62 (95% CI 1.52-1.73; P < 0.000; I2 = 90.8%). The relative risk was 1.80 (95% CI 1.58-2.03; P < 0.000; I2 = 93.2%) for case-control studies and 1.51 (95% CI 1.39-1.64; P < 0.000; I2 = 88.0%) for cohort studies. The association persisted across subgroups of geographical location, study design, risk factors, defined daily dose, duration of use, fracture site, study period, and after adjustment for depression, physical activity, gender, and age. Studies adjusting for bone mineral density and osteoporosis showed lesser fracture risk, though numerical estimates were not provided in the abstract.
Why it matters
This review synthesizes observational evidence indicating a consistent association between SSRI therapy and increased fracture risk, suggesting bone health should be considered during treatment.
Limits
The analysis relied exclusively on observational studies, which cannot establish causality. Statistical heterogeneity was very high across all pooled comparisons (I2 > 88%), total participant sample size was not reported in the abstract, and residual confounding by indication or fall risk remains possible.
Cited by
- context A standard dose of Prozac (fluoxetine) causes as much damage to bone integrity as extended use of prednisone.