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Impact of Antiepileptic Therapy on Bone-Mineral Density in Young Women
Phenytoin — but not carbamazepine, lamotrigine, or valproate — reduced bone-mineral density at the femoral neck over a 1-year period.
Antiepileptic drug (AED) therapy has been associated with decreased bone-mineral density (BMD) and increased risk for osteoporotic fractures. Whether certain AEDs are more detrimental to bone than others is unclear. In this 1-year longitudinal study, partially supported by the manufacturer of lamotrigine, researchers followed 93 women (all premenopausal with normal menses; mean age, 32) on AED monotherapy. The AEDs were carbamazepine (n=41), lamotrigine (n=23), valproate (n=14), and phenytoin (n=15). At baseline and 1 year later, the authors measured BMD at the lumbar spine and hip, markers of bone turnover, and serum calciotropic hormone levels.
The 93 subjects were well matched at baseline. At 1 year, the women on phenytoin sustained a significant 2.6% decline in BMD at the femoral neck. No other groups lost BMD at any site. In the phenytoin group, lower vitamin D levels were associated with secondary hyperparathyroidism and higher bone resorption.
Comment: There is both good and bad news in this study. The good news is that in women taking AEDs for an average of 9 years, BMD was normal at baseline and did not decline over 1 year. The bad news is that women taking phenytoin sustained a significant decline in BMD at the femoral neck in 1 year. Although the mechanism of bone loss in the phenytoin-treated patients is unknown, the hormonal findings in this group raise the question of whether aggressive vitamin D supplementation might prevent bone loss in patients taking phenytoin. An obvious weakness of the study is the lack of a control group. Larger controlled studies are needed to confirm or refute these preliminary findings.
— Carolyn B. Becker, MD
Dr. Becker is Master Clinician, Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women’s Hospital, and Associate Professor of Medicine, Harvard Medical School, Boston.
Published in Journal Watch Neurology June 17, 2008
Citation(s):
Pack AM et al. Bone health in young women with epilepsy after one year of antiepileptic drug monotherapy. Neurology 2008 Apr 29; 70:1586.
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