The effect of vitamin K2 on bone metabolism in aged female rats

Wataru Sakamoto, Haruo Isomura, Katsutoshi Fujie, Tadashi Iizuka, Jun Nishihira, Gen Tatebe, Kazuhiko Takahashi, Yusuke Osaki, Michio Komai, Hiroshi Tamai

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)


Reactive oxygen species (ROS) may contribute to aging and osteoporosis resulting from marked decreases in plasma antioxidants in aged osteoporotic women. On the other hand, high-dose vitamin K2 (menaquinone-4: menatrenone, MK-4) supplementation has been reported to reduce ovariectomy-induced bone loss in rats and to decrease osteoporotic fracture in postmenopausal women. However, the mechanism by which vitamin K2 prevents osteoporosis is unclear. Recently, vitamin K2 has been suggested to preserve antioxidant activity as a novel function. Therefore, we investigated the effect of vitamin K2 on the osteoporosis of aged rats by evaluating the relationships between serum antioxidant levels and bone metabolism. Aged female rats exhibited significantly lower serum alkaline phosphatase activity and osteocalcin level, together with lower serum levels of antioxidants such as 17β-estradiol, macrophage migration inhibitory factor (MIF) and glutathione peroxidase (GPx) activity, as compared with young female rats. On the other hand, vitamin K2 supplementation (500 mg/kg, food intake) for 98 days led to a significantly increased serum vitamin K2 level (3,045 ± 915 ng/ml in the vitamin K2 supplemented group vs. 4.6 ± 3.4 ng/ml in the control diet group; P < 0.0001) with increased serum alkaline phosphatase activity and MIF level (P < 0.05). Unexpectedly, however, it failed to increase the serum level of antioxidants such as GPx. Nor did it affect bone metabolism markers such as oteocalcin and osteopontin, which were significantly lower than in the young female rats (P < 0.05). Finally, the histomorphometric properties of the proximal tibia in the femur were not altered by vitamin K2. These results suggest that high-dose vitamin K2 supplementation neither improves lowered antioxidant levels nor stimulates bone formation in aged rats.

Original languageEnglish
Pages (from-to)1604-1610
Number of pages7
JournalOsteoporosis International
Issue number12
Publication statusPublished - 2005 Dec


  • Aged female rat
  • Bone metabolism
  • Glutathione peroxidase
  • Vitamin K

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism


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