OBJECTIVE: We investigated the effects of phenytoin, an antiepileptic drug, and vitamin K2 (menatetrenone) on bone mineral density and the changes in the levels of menaquinone derivatives (MK-1 ∼ MK-14) in the sera and femurs of growing male rats. METHODS: Levels of menaquinone derivatives were measured with high-performance liquid chromatography with an electrochemical detector. RESULTS: Bone mineral density values decreased significantly in all parts of the femoral bones measured (diaphysis and metaphysis) in the phenytoin-treated group. When the serum and bone levels of menatetrenone and MK-6 decreased due to phenytoin administration, we observed bone loss in rats. Conversely, when bone loss was prevented by the combined administration of phenytoin and menatetrenone, serum and bone levels of menatetrenone and MK-6 increased to the levels of vehicle-treated rats. CONCLUSIONS: Long-term phenytoin exposure may inhibit bone formation concomitantly with insufficient vitamin K, which, at least in part, contributes to bone loss in rats.
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