Effects of menatetrenone on the bone and serum levels of vitamin K2 (menaquinone derivatives) in osteopenia induced by phenytoin in growing rats.
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 approximately 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.
Onodera
Kenji
K
Department of Dental Pharmacology, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan. onoderak@md.okayama-u.ac.jp
Takahashi
Atsushi
A
Wakabayashi
Hiroyuki
H
Kamei
Jyunzo
J
Sakurada
Shinobu
S
D000818:Animals; D000927:Anticonvulsants / Q000009:adverse effects; D015519:Bone Density / Q000187:drug effects*; D001851:Bone Diseases, Metabolic / Q000139:chemically induced / Q000517:prevention & control*; D005269:Femur / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010672:Phenytoin / Q000009:adverse effects; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D024482:Vitamin K 2 / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology* / Q000627:therapeutic use
D000927:Anticonvulsants; D024482:Vitamin K 2; C030814:menatetrenone; D010672:Phenytoin