Fwd: [CNS_Healing] Long-Term Valproic Acid Use Linked to Decreased Bone Miner...

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Long-Term Valproic Acid Use Linked to Decreased Bone Mineral Density

WESTPORT, CT (Reuters Health) Aug 22 - Long-term valproic acid (VPA) use can increase bone resorption in adult epileptic patients and lead to a decreased bone mineral density.

Previous studies have shown that phenytoin and other antiepileptic agents can affect bone metabolism, but the few studies that have examined the effects of VPA have been limited to small pediatric populations, Dr. Yoshihiro Sato, from Hirosaki University in Japan, and colleagues note in the August 14th issue of Neurology.

Dr. Sato's team assessed the bone-related outcomes of 40 adult epileptic patients who received VPA monotherapy for over 1 year. The outcomes of these patients were compared with those of 40 matched patients who received phenytoin monotherapy for over 1 year and with those of 40 healthy control subjects.

VPA- and phenytoin-treated patients had bone mineral density values that were about 14% lower than those of control subjects, the authors note. Nine VPA-treated patients had laboratory findings suggestive of osteoporosis and 15 had findings consistent with osteopenia.

In the VPA group, serum calcium levels were significantly higher than those of the other groups, and the phenytoin group had levels that were significantly lower, the researchers report. Serum levels of bone Gla protein, a bone formation marker, and pyridinoline cross-linked carboxy-terminal telopeptide of type I collage (ICTP), a bone resorption marker, were higher in the treatment groups than in the control group.

Many antiepileptics are potent inducers of hepatic microsomal enzymes that can promote bone demineralization, the researchers note. However, because VPA does not induce these enzymes, they were somewhat surprised by the findings.

"Because patients under treatment for epilepsy are at increased risk for osteoporosis, serum concentrations of a bone resorption marker such as ICTP as well as ionized calcium should be measured routinely during long-term VPA therapy," the researchers recommend.

They add that "controlled trials are required to determine whether treatment with bisphosphonates or calcitonin might be of benefit in preventing osteoclastic bone resorption and consequent hypercalcemia" in VPA-treated patients.

Neurology 2001;57:445-449.

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