Effects of menatetrenone on prednisolone-induced bone loss in rats.
This study was carried out to evaluate the effect of menatetrenone, a vitamin K2 with 4 isoprene units, on prednisolone-induced bone loss. Three experiments were performed in rats which received menatetrenone as a dietary supplement. In experiment 1, a soluble form of prednisolone, dissolved in drinking water, was administered to rats at 7 mg/kg/day for 9 weeks. The length, dry weight, and bone density of femurs and tibiae, as well as urinary gamma-carboxyglutamic acid (Gla) content, were significantly lower in the prednisolone-control group than in the intact group. Menatetrenone (17 mg/kg/day) significantly inhibited the decrease in these bone parameters, especially in tibiae, and completely inhibited the decrease in urinary Gla content. In experiments 2 and 3, prednisolone (10 mg/kg), dissolved in cottonseed oil, was given to rats intramuscularly three times a week for 4 and 10 weeks, respectively. In experiment 2, bone length, bone strength and calcium content in the femur were reduced by 4-week prednisolone treatment. These reductions were significantly improved by menatetrenone (21 mg/kg/day). In experiment 3, 10-week prednisolone treatment reduced bone length and the calcium and hydroxyproline content of the femur. Menatetrenone (0.4, 10, and 50 mg/kg/day) significantly inhibited the reduction of calcium content in the femur. These results suggest that menatetrenone may inhibit the bone loss induced by corticosteroid treatment.
Hara
K
K
Department of Drug Research II, Eisai Co., Ltd., Tokyo, Japan.
Akiyama
Y
Y
Ohkawa
I
I
Tajima
T
T
D000818:Animals; D001862:Bone Resorption / Q000097:blood / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D011239:Prednisolone / Q000037:antagonists & inhibitors*; D051381:Rats; D011916:Rats, Inbred F344; D014812:Vitamin K / Q000031:analogs & derivatives* / Q000494:pharmacology; D024482:Vitamin K 2 / Q000031:analogs & derivatives
D024482:Vitamin K 2; D014812:Vitamin K; C030814:menatetrenone; D011239:Prednisolone