2001 Fiscal Year Final Research Report Summary
THE ROLE OF VITAMN K2 ON THE MECHANISM OF OSTEOPENIA INDUCED BY PHENYTOIN ADMINISTRATION
| Project/Area Number |
12671796
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Functional basic dentistry
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| Research Institution | OKAYAMA UNIVERSITY |
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Principal Investigator |
ONODERA Kenji DEPARTMENT OF DENTAL PHARMACOLOGY, OKAYAMA UNIVERSITY, GRADUATE SCHOOL OF MEDICINE AND DENTISTRY, ASSOCIATED PROFESSOR, 大学院・医歯学総合研究科, 助教授 (40133988)
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| Co-Investigator(Kenkyū-buntansha) |
SOGAWA Norio DEPARTMENT OF DENTAL PHARMACOLOGY, OKAYAMA UNIVERSITY, GRADUATE SCHOOL OF MEDICINE AND DENTISTRY, ASSISTANT PROFESSOR, 大学院・医歯学総合研究科, 助手 (30236153)
SAITOU Takashi CLINICS OF DENTISTRY FOR THE DISABLED, TOHOKU UNIVERSITY DENTAL HOSPITAL, ASSOCIATED PROFESSOR, 歯学部・附属病院, 助教授 (90005108)
SHINODA Hisashi DEPARTMENT OF DENTAL BIOLOGY, TOHOKU UNIVERSITY, GRADUATE SCHOOL OF DENTISTRY, PROFESSOR, 大学院・歯学研究科, 教授 (80014025)
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| Project Period (FY) |
2000 – 2001
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| Keywords | Drug-induced osteopenia / Vitamin K2 / Phenytoin / Osteocalcin / Bone Mineral Density / Menatetrenone / Femoral bone / HPLC |
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| Research Abstract |
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. 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.
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[Publications] Onodera, K., Takahashi, A., Mayanagi, S., Wakabayashi, H., Kamei, J., Shinoda, H.: "Phenytoin-induced bone loss and its prevention with alfacalcidol or calcitriol in growing rats"Calcified Tissue Internatioanal. 69. 109-116 (2001)
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