Calcium, vitamin D urged for epilepsy patients

Timothy F. Kirn

SEATTLE -- Bone loss in epilepsy patients is a serious problem that has not received enough attention, experts said at the annual meeting of the American Epilepsy Society.

Some of those experts urged that all epilepsy patients, regardless of the medications they might be on, should receive calcium and vitamin D supplementation.

Among the new information presented at the meeting was a retrospective study of 50 adult, male patients. Only 18% of those men got adequate exercise and only 12% got the daily recommended amount of calcium in their diet. Of five patients who underwent a bone scan, three had osteopenia/osteoporosis; they were 32 years, 47 years, and 52 years of age, and had had epilepsy since childhood.

Another study compared young patients on a ketogenic diet with young patients about to start the diet. All of the patients had been on multiple drugs, all had low bone density, and all were significantly below their expected height and weight.

Physicians who treat epileptic patients need a "wake-up call," said Dr. Richard H. Mattson, professor of neurology, Yale University, New Haven. Reports of fractures and osteoporosis associated with drug treatment of epilepsy date back to the late 1960s, yet the significance of those reports has not been fully appreciated.

Dr. Mattson said that he has been remiss himself in taking such reports too lightly. In the mid-1980s, he attended a conference in Europe at which the problem was discussed.

Most of the data came from Northern European countries and institutionalized patients, and he assumed that the patients simply did not get enough sun. "That conclusion, I have now decided, was incorrect," he said. A survey published in 2001 found that only 27% of neurologists screened their epilepsy patients for bone loss; only 7% advised their patients to take calcium and vitamin D supplements. "In my opinion, that is not adequate," Dr. Mattson said.

There are no figures on how frequently patients experience bone loss, and the literature is deficient in prospective clinical trials that have looked at the problem, said Dr. Mattson, who is one of the authors of the largest epilepsy drug trial ever conducted, the VA Epilepsy Cooperative Study That study failed to take note of fractures as adverse events.

A Swedish study of institutionalized patients reported that 10% sustained a fracture per year. Other reports suggest that epilepsy patients are at risk for rickets or osteomalacia, and poor dentition.

One of the earliest attempts to explain why epilepsy drugs might contribute to bone loss postulated that drugs such as phenytoin, phenobarbital, and carbamazepine might interfere with vitamin D metabolism by inhibiting cytochrome P450-mediated reactions. But valproate, which does not affect that enzyme, has been shown to cause bone loss.

Newer agents may not be free of bone effects, despite hopes that the bone problem would "fade into history" as a result of greater reliance on newer antiepileptic medications-levetiracetam, topiramate, and zonisamide, Dr. Mattson said. Topiramate, for example, can interfere with oral contraceptive effectiveness, and vitamin D and estradiol are somewhat similar molecules.

The survey of 50 adult male subjects (mean age 41 years) was designed to evaluate 15 primary and secondary risk factors known to be associated with osteoporosis.

In 74% of the subjects, the onset of epilepsy came before age 25, which is the age of peak bone density attainment in males, Dr. Mercedes P. Jacobson of Temple University, Philadelphia, said in a poster presentation.

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