Phenytoin and Bone Health

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Summary and Comment

Phenytoin and Bone Health

Phenytoin monotherapy was associated with lower femoral neck BMD.

Antiepileptic drugs (AEDs) have adverse effects on bone health, but longitudinal studies of single agents have been lacking. Investigators evaluated bone loss during 1 year in 93 premenopausal women with epilepsy (age range, 18–40) who were receiving AED monotherapy with carbamazepine (41 women), lamotrigine (23), phenytoin (15), or valproate (14). Measurements at baseline and 1 year included lumbar spine, femoral neck, and total hip BMD, as well as biochemical markers of bone metabolism. All women completed nutritional and activity questionnaires; data on duration and dose of current AED treatment and total duration of AED treatment also were obtained.

Participants reported that they were physically active, generally with daily calcium intakes of >1000 mg. At 1 year follow-up, femoral neck BMD was significantly reduced from baseline (2.6%) in the phenytoin group; BMD remained stable in all other groups and at all other measurement sites. Markers of bone turnover showed no change except for a decline in urine N-telopeptide levels (a marker of bone resorption) in the phenytoin group. Parathyroid hormone levels increased only in the phenytoin group.

Comment: Childhood, early adolescence, and young adulthood are crucial periods for osteoporosis prevention. The goal is for women to maximize bone accretion during these formative years and to minimize loss during the reproductive years and as menopause approaches. Because phenytoin seemed to have a negative effect on bone health in this study, these results could be cause for concern; but given the study’s limitations (short follow-up interval, no randomization, no normal controls, and lack of preteen and teenage participants), recommending changes to existing practice is difficult. In further studies, researchers should address whether current or prior use of phenytoin is associated with high fracture risk. Meanwhile, if phenytoin is providing effective anticonvulsant therapy for an individual woman, the present results do not suggest that the AED should be changed.

— Ann J. Davis, MD

Published in Journal Watch Women's Health June 26, 2008