title: Menatetrenone rescues bone loss by improving osteoblast dysfunction in rats immobilized by sciatic neurectomy.
abstract: Menatetrenone (MK-4) is a vitamin K2 homologue that has been used as a therapeutic agent for osteoporosis in Japan. However, there is no far any reported evidence that MK-4 ameliorates a pre-existing condition of reduced bone mineral density (BMD) in vivo. In this study, we evaluated the effect of MK-4 in a rat model of established bone loss through immobilization caused by sciatic neurectomy. Unilateral sciatic neurectomy (SNx) was performed in rats, and 10 or 30 mg/kg of MK-4 or vehicle was administered to the rats three weeks after operation. Seven weeks after operation, the rats were sacrificed and BMD and bone histomorphometric parameters were measured to assess the effects of MK-4. While BMD of the distal femoral metaphysis was significantly decreased after SNx, MK-4 administration increased BMD in the neurectomized rats. Bone formation was decreased continuously and bone resorption was initially increased in SNx rats. Four weeks treatment of MK-4 increased bone formation and suppressed bone resorption. In addition, increased carboxylated osteocalcin and decreased undercarboxylated osteocalcin in serum were observed in MK-4-administered rats. These results indicated that MK-4 rescued bone volume by improving osteoblast dysfunction and accelerating gamma carboxylation of osteocalcin. MK-4 may be useful for treating disuse osteopenia.
authors.affiliation: Department of Health Sciences, Oita University of Nursing and Health Sciences, 2944-9, Megusuno, Notsuharu, Oita 870-1201, Japan.
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Iwasaki-Ishizuka
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Yamato
authors.forename: Hisashi
authors.initials: H
authors.lastname: Murayama
authors.forename: Ikuko
authors.initials: I
authors.lastname: Ezawa
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Kurokawa
authors.forename: Masafumi
authors.initials: M
authors.lastname: Fukagawa
mesh_terms: D000818:Animals; D015519:Bone Density; D001862:Bone Resorption / Q000517:prevention & control; D004195:Disease Models, Animal; D008297:Male; D010006:Osteoblasts / Q000187:drug effects* / Q000502:physiology; D015675:Osteocalcin / Q000097:blood; D010012:Osteogenesis / Q000187:drug effects; D010024:Osteoporosis / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000601:surgery; D024482:Vitamin K 2 / Q000031:analogs & derivatives* / Q000494:pharmacology*
chemical_list: D015675:Osteocalcin; D024482:Vitamin K 2; C030814:menatetrenone