ABSTRACT-The effects of menatetrenone, a vitamin K2 homologue, on bone loss induced by ovariectomy in rats were studied in 3 experiments. Menatetrenone was given as a dietary supplement. In experiment 1, at 2 weeks postovariectomy, menatetrenone (10 mg/kg/day given for 2 weeks) inhibited the decrease in bone density of the femoral metaphysis induced by the ovariectomy. In experiment 2, menatetrenone (3 or 30 mg/kg/day given for 6 months) inhibited the decrease in bone strength of the femur and the decrease in calcium and hydroxyproline content of the femoral diaphysis at 6 months postovariectomy. In experiment 3, menatetrenone treatment, at 30 or 100 mg/kg/day for 6 months, protected against the decrease in bone strength and calcium and hydroxyproline content in the bone loss model induced by ovariectomy and calcium-deficient diet. These findings suggest that menatetrenone protects against the bone loss induced by ovariectomy.
Keywords:Menatetrenone, Ovariectomy, Bone lossSince Bouckaert and Said first reported the effect of vitamin K on fracture healing in 1960 (1), several studies have suggested that this vitamin affects bone metabolism. Hall et al. reported that some infants whose mothers had received oral anticoagulant therapy during pregnancy had hypoplasia of the nasal bone (2). Hart et al. demonstrated that circulating levels of vitamin K, in osteoporotic patients with fractures were significantly lower than those in age-matched control subjects (3). It is well-known that vitamin K is essential for the r-carboxylation of osteocal cin (4), a non-collagenous protein present in bone (5, 6). Although the role of osteocalcin in bone metabolism remains obscure, it is possible that vitamin K may play a role in bone metabolism via this substance.Two types of vitamin K occur in nature: vitamin K, (phylloquinone, 2-methyl-3-phytyl-1,4-naphthoquinone), which is derived from plants, and vitamin K2 (menaqui nones), a series of vitamers with multi-isoprene units at the 3-position. In the present studies, we assessed the effects of menatetrenone (2-methyl-3 -all-trans-tetra prenyl-1,4-naphthoquinone), a vitamin K2 with four isoprene units, on bone loss induced by ovariectomy in rats in three different experiments: In experiment 1, we examined its effects on early metaphysial bone loss in the femur; in experiment 2, we studied its effects on the de velopment of bone loss induced by ovariectomy over a 6-month period; and in experiment 3, we studied its cura tive effects over 6 months on bone loss induced by ovariec tomy and a calcium-deficient diet.
MATERIALS AND METHODS
AnimalsFor experiment 1, we used 20-week-old female Fischer rats (Clea Japan, Inc., Tokyo); and for experiments 2 and 3, we used 40-week-old female Sprague-Dawley rats (Charles River Japan, Inc., Tokyo). The animals were housed in a room maintained at 261C with a 12-hr light dark cycle and were given free access to food and distilled water. All operations were performed under pentobar bital anesthesia.
Experiment 1Twenty rats underwent bilateral ovariecto...
