Antiepileptic drug use, falls, fractures, and BMD in postmenopausal women: Findings from the Women's Health Initiative (WHI)

Antiepileptic drugs (AEDs) are used increasingly in clinical practice to treat a number of conditions. However, the relationship between the use of these medications, particularly the newer AEDs, and fracture risk has not been well characterized. We used data from the Women's Health Initiative (WHI) to determine the relationship bewteen the use of AEDs and falls, fractures, and bone mineral density (BMD) over an average of 7.7 years of follow-up. We included 138,667 women (1,385 users of AEDs and 137,282 nonusers) aged 50 to 79 years in this longitudinal cohort analyses. After adjustment for covariates, use of AEDs was positively associated with total fractures [hazard ratio (HR)=1.44, 95% confidence interval (CI) 1.30-1.61], all site-specific fractures including the hip (HR=1.51, 95% CI 1.05-2.17), clinical vertebral fractures (HR=1.60, 95% CI 1.20-2.12), lower arm or wrist fractures (HR=1.40, 95% CI 1.11-1.76), and other clinical fractures (HR=1.46, 95% CI 1.29-1.65) and two or more falls (HR=1.62, 95% CI 1.50-1.74) but not with baseline BMD or changes in BMD (p≥.064 for all sites). Use of more than one and use of enzyme-inducing AEDs were significantly associated with total fractures (HR=1.55, 95% CI 1.15-2.09 and HR=1.36, 95% CI 1.09-1.69, respectively). We conclude that in clinical practice, postmenopausal women who use AEDs should be considered at increased risk for fracture, and attention to fall prevention may be particularly important in these women.