Do Selective Serotonin Reuptake Inhibitors (SSRIs) Cause Fractures?

Area of Science:

• Pharmacovigilance
• Bone Health
• Epidemiology

Background:

• Meta-analyses indicate a 70% fracture risk increase in SSRI users.
• Observational studies limit causal inference due to confounding factors.

Purpose of the Study:

• To evaluate the causality between SSRI use and fractures using Bradford Hill criteria.
• To explore potential mechanisms and clinical implications of this association.

Main Methods:

• Application of Bradford Hill criteria to existing observational data.
• Analysis of self-controlled case series studies to mitigate bias.
• Review of evidence for biological gradient, specificity, and plausibility.

Main Results:

• A consistent temporal relationship and biological gradient observed between SSRIs and fractures.
• Falls identified as a significant contributor to fractures in SSRI users.
• Specificity and biological plausibility remain areas of concern, requiring further investigation.

Conclusions:

• SSRIs appear to contribute to falls, thereby increasing fracture risk.
• Current evidence is insufficient to definitively label SSRIs as a direct cause of osteoporosis.
• Targeting fall risk in SSRI users and considering bone health assessments are recommended clinical strategies.