Not All Antiepileptic Drugs Are Created Equal When It Comes to Bone Health

April 18, 2005
Internal Medicine World Report, April 2005,

Not All Antiepileptic Drugs Are Created Equal When It Comes to Bone Health

By Rosemary Frei, MSc

NEW ORLEANS—Recent evidence suggests that significant differences exist between the antiepileptic drugs (AEDs) in terms of their effects on bone parameters, putting some patients at risk for fractures or other complications.

A prospective study funded by GlaxoSmithKline has shown that 11 women who had been taking phenytoin (Dilantin) for at least 8 years had an average 2.75% decrease in bone mineral density (BMD) at the femoral neck after 1 year of study. This was a significantly greater loss than found in women taking other drugs, including carbamazepine (Tegretol), valproate (Depakote), or lamotrigine (Lamictal).

This study was presented at the last meeting of the American Epilepsy Society and published in the Annals of Neurology (2005;57:252-257).

Lead investigator Alison Pack, MD, of Columbia University, New York, says women taking AEDs that put them at risk for bone loss, who are postmenopausal and/or who smoke, are small-framed or take glucocorticosteroids or heparin should have regular dual-energy x-ray absorptiometry (DXA) scans. All patients taking AEDs, regardless of age or sex, should be encouraged to take >400 IU/day of vitamin D and the recommended daily allowance of calcium, she added.

Gabriel Ronen, MD, MSc, and Stephanie Atkinson, PhD, both of McMaster University, Hamilton, Ontario, have also studied the effects of long-term AEDs, suggesting that more research is needed in this area. “We need longitudinal, controlled studies, not just cross-sectional studies such as Dr Pack’s,” said Dr Ronen.

He added that men receiving long-term AEDs also should have regular DXA scans, and that patients who have had epilepsy since childhood or are taking >1 AED may be at particular risk for bone loss.

Dr Pack and colleagues studied 11 premenopausal women taking phenytoin, 37 women taking carbamazepine, 18 women taking valproate, and 19 women taking lamotrigine. Those using lamotrigine had been taking the drug for a significantly shorter period—21 months—than those taking the other medications—97 months for phenytoin and 66 months for either carbamazepine or valproate (P <.001). However, “the duration of lamotrigine treatment was sufficient to affect the indices of mineral metabolism and markers of bone turnover,” she said.

Serum calcium concentrations were significantly lower in women receiving carbamazepine, phenytoin, or valproate than in those taking lamotrigine (P = .008). Patients taking phenytoin also had significantly higher bone-specific alkaline phosphatase concentrations than those taking the other 3 AEDs (P = .007).

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