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

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 17-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.