Menatetrenone (MK-4) inhibits bone resorption and enhances osteoblast-induced mineralization. In this study, we examined whether MK-4 administration had beneficial effects on osteoblast dysfunction and trabecular microstructure as well as on bone volume loss in a rat model of osteopenia. Male Sprague-Dawley rats were neurectomized and administered MK-4 as a daily supplement. On Day 21 after neurectomy, significant bone loss was observed in the positive control rats. MK-4 prevented the decrease in bone mineral density of the distal metaphysis of the femur. The osteoclast surface per bone surface (Oc.S/BS) and the number of osteoclasts per bone perimeter (N.Oc/B.Pm) were reduced and the mineral apposition rate (MAR) decreased in the immobilized rats on Day 42, suggesting suppression of bone turnover. In contrast, administration with a low dose of menatetrenone led to an increase of MAR and bone formation rate (BFR), while Oc.S/BS and N.Oc/B.Pm remained at normal levels. These data suggested that MK-4 reduced the loss of trabecular bone, prevented osteoblast dysfunction to a certain extent, and contributed to preservation of the trabecular microstructure in this rat model of osteopenia induced by sciatic neurectomy.
The Japanese Pharmacological Society 2002