title: The effect of vitamin K2 on bone metabolism in aged female rats.
abstract: 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 17beta-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 osteocalcin 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.
authors.affiliation: Department of Biochemistry, School of Dentistry, Hokkaido University, 060-8586, Sapporo, Japan. sakamoto@den.hokudai.ac.jp
authors.forename: Wataru
authors.initials: W
authors.lastname: Sakamoto
authors.forename: Haruo
authors.initials: H
authors.lastname: Isomura
authors.forename: Katsutoshi
authors.initials: K
authors.lastname: Fujie
authors.forename: Tadashi
authors.initials: T
authors.lastname: Iizuka
authors.forename: Jun
authors.initials: J
authors.lastname: Nishihira
authors.forename: Gen
authors.initials: G
authors.lastname: Tatebe
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Takahashi
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Osaki
authors.forename: Michio
authors.initials: M
authors.lastname: Komai
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tamai
mesh_terms: D000367:Age Factors; D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D000975:Antioxidants / Q000032:analysis; D015415:Biomarkers / Q000032:analysis; D001842:Bone and Bones / Q000378:metabolism* / Q000473:pathology; D002118:Calcium / Q000097:blood; D019587:Dietary Supplements; D005260:Female; D005979:Glutathione Peroxidase / Q000097:blood; D015675:Osteocalcin / Q000097:blood; D010010:Osteoclasts / Q000473:pathology; D053495:Osteopontin; D010024:Osteoporosis / Q000178:diet therapy / Q000378:metabolism*; D010758:Phosphorus / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D012795:Sialoglycoproteins / Q000097:blood; D024482:Vitamin K 2 / Q000008:administration & dosage* / Q000097:blood; D015430:Weight Gain / Q000187:drug effects
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D012795:Sialoglycoproteins; C506897:Spp1 protein, rat; D015675:Osteocalcin; D053495:Osteopontin; D024482:Vitamin K 2; D010758:Phosphorus; D005979:Glutathione Peroxidase; D000469:Alkaline Phosphatase; D002118:Calcium