Background Selective serotonin reuptake inhibitors (SSRIs) were recently approved by the FDA to treat vasomotor symptoms associated with menopause. No prior study has directly examined whether fracture risk is increased among perimenopausal women who initiate SSRIs or among a population of women without mental disorders more generally.

Methods Female patients without mental illness, aged 40–64 years, who initiated SSRIs were compared with a cohort who initiated H2 antagonists (H2As) or proton-pump inhibitors (PPIs) in 1998–2010, using data from a claims database. Standardised mortality ratio weighting was applied using the propensity score odds of treatment to adapt the distribution of characteristics among patients starting H2A/PPIs to the distribution among SSRI initiators. Poisson regression estimated risk differences and Cox proportional hazards regression the RR of fractures among new users of SSRIs versus H2A/PPIs. Primary analyses allowed for a 6-month lag period (ie, exposure begins 6 months after initiation) to account for a hypothesised delay in the onset of any clinically meaningful effect of SSRIs on bone mineral density.

Results Fracture rates were higher among the 137 031 SSRI initiators compared with the 236 294 H2A/PPI initiators, with HRs (SSRI vs H2A/PPI) over 1, 2 and 5 years of 1.76 (95% CI 1.33 to 2.32), 1.73 (95% CI 1.33 to 2.24) and 1.67 (95% CI 1.30 to 2.14), respectively.

Conclusions SSRIs appear to increase fracture risk among middle-aged women without psychiatric disorders, an effect sustained over time, suggesting that shorter duration of treatment may decrease fracture risk. Future efforts should examine whether this association pertains at lower doses.