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Antiepileptic drug use increases rates of bone loss in older women

A prospective study

From the Department of Medicine and Center for Chronic Disease Outcomes Research (Dr. K.E. Ensrud), VA Medical Center, and Division of Epidemiology (Dr. K.E. Ensrud, P.J. Bowman), School of Public Health, University of Minnesota, Minnesota Comprehensive Epilepsy Program (Dr. Walczak), and Noran Neurological Clinic (Dr. E.R. Ensrud), Minneapolis, MN; and Department of Epidemiology and Biostatistics (T. Blackwell and K.L. Stone), University of California, San Francisco.

Address correspondence and reprint requests to Dr. K.E. Ensrud, Department of Medicine 111-0, VA Medical Center, One Veterans Dr., Minneapolis, MN 55417; e-mail: ensru001{at}tc.umn.edu

Objective: To test the hypothesis that older women with antiepileptic drug (AED) use have increased rates of bone loss.

Methods: AED use was ascertained and calcaneal and hip bone mineral density (BMD) measured in a cohort of 9,704 elderly community-dwelling women enrolled in the Study of Osteoporotic Fractures, and they were followed prospectively for changes in BMD. Current use of AED was assessed by interview, with verification of use from medication containers at baseline and follow-up examinations. Women were classified as continuous users, partial (intermittent) users, or nonusers. Rates of change in BMD were measured at the total hip and two subregions (average 4.4 years between examinations) and at the calcaneus (average 5.7 years between examinations).

Results: After adjustment for confounders, the average rate of decline in total hip BMD steadily increased from –0.70%/year in nonusers to –0.87%/year in partial AED users to –1.16%/year in continuous AED users (p value for trend = 0.015). Higher rates of bone loss were also observed among continuous AED users at subregions of the hip and at the calcaneus. In particular, continuous phenytoin users had an adjusted 1.8-fold greater mean rate of loss at the calcaneus compared with nonusers of AED (–2.68 vs –1.46%/year; p < 0.001) and an adjusted 1.7-fold greater mean rate of loss at the total hip compared with nonusers of AED (–1.16 vs –0.70%/year; p = 0.069).

Conclusions: Continuous AED use in elderly women is associated with increased rates of bone loss at the calcaneus and hip. If unabated, the rate of hip bone loss among continuous AED users is sufficient to increase the risk of hip fracture by 29% over 5 years among women age 65 years and older.

Received June 24, 2003. Accepted in final form January 12, 2004.

Additional material related to this article can be found on the Neurology Web site. Go to www.neurology.org and scroll down the Table of Contents for the June 8 issue to find the title link for this article.

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