SSRI use and risk of fractures among perimenopausal women without mental disorders

Abstract

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 protonpump 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.

Selective serotonin reuptake inhibitor and selective serotonin and norepinephrine reuptake inhibitor use and risk of fractures in adults: A systematic review and meta‐analysis

“…No relevant randomized controlled studies were found. Sixteen studies were included from the previous systematic review, and 17 studies were identified as new in the databases (Figure ) …”

“…The studies we found were published between 1998 and 2016, with 11 studies since 2013 . Two studies were reported across multiple articles and each was treated as a single distinct study: Vestergaard et al and Souverein et al One study reported results from both a cohort and a nested case‐control analysis .…”

“…Data on SSRI and SNRI use were retrieved either from the national prescription database or self‐reported and verified from drug containers. Thirteen studies categorized participants into current, recent, or past users …”

Selective serotonin re-uptake inhibitor sertraline inhibits bone healing in a calvarial defect model

“…These data suggest that there is a susceptible population of patients with impaired bone health due to pharmacological intervention for depression once thought to only include patients with pre-existing compromised bone (i.e., osteoporosis). 2–5 Although this topic will remain controversial, the increase in reports of interaction effects between bone health and SSRI use 14,26 is revealing a potentially larger problem not limited to osteoporosis. Further study is needed to determine if long-term SSRI treatment alters bone remodelling through other pathways such as TNF-α signalling linked to inflammation and early healing.…”

“…14 While clinical correlations between SSRI treatment and negative bone phenotypes have been established, research concerning SSRI use and bone health has only recently been extended to specific effects on bone wound healing, where it was found that fluoxetine negatively affected limb fracture healing. 15 It follows that if SSRIs can affect bone health and even bone cell activity, 16–19 use may negatively affect the repair and remodelling process.…”