Effects of phenytoin and/or vitamin K2 (menatetrenone) on bone mineral density in the tibiae of growing rats

Kenji Onodera, Atsushi Takahashi, Shinobu Sakurada, Yoshiro Okano

Research output: Contribution to journalArticlepeer-review

43 Citations (Scopus)


In this study, we investigated 1) whether the administration of phenytoin induced bone loss; and 2) whether menatetrenone could prevent bone loss induced by phenytoin. For this purpose, we previously developed a procedure to measure the bone mineral density using a conventional X-ray absorptiometry method. A long-termed administration of phenytoin (20 mg/kg per day for 5 weeks) produced bone loss in the tibiae of growing rats. The values of bone mineral density (BMD) were significantly decreased in the tibial diaphysis and metaphysis in the phenytoin-treated group. In this period, we measured the serum level of vitamin K-dependent protein, osteocalcin, a marker of bone formation. The serum level of osteocalcin showed a decrease in the phenytoin-treated group compared with the vehicle-treated group. Combined administration of menatetrenone (30 mg/kg in diet per day) with phenytoin for 5 weeks prevented the reduction of BMD, and the level of osteocalcin was slightly increased. Thus, it is suggested that long-termed phenytoin exposure may inhibit bone formation concomitantly with insufficient vitamin K, which, at least in part, contributed to bone loss in rats. Finally, these findings implicated the therapeutic usefulness of menatetrenone on a moderate degree of bone abnormality such as drug-induced osteopenia.

Original languageEnglish
Pages (from-to)1533-1542
Number of pages10
JournalLife Sciences
Issue number13
Publication statusPublished - 2002 Feb 15


  • Bone mineral density
  • Osteopenia
  • Phenytoin
  • Vitamin K

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)


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