Yasuhiro Akiyama (1), Kuniko Hara (1), Masatoshi Kobayashi (1), Takashi
Tomiuga (1) and Tetsuya Nakamura (2)
(1) Department of Applied Drug Research, (2) Vitamin E Information and
Technology Section, Eisai Co., Ltd., Koishikawa 4-6-10, Bunkyo-ku, Tokyo
112-8088, Japan
Abstract: To clarify how vitamin K2 prevents bone
loss in vivo, it was given to ovariectomized 20-week-old rats for 2 weeks.
Bone mineral density (BMD) in the whole femur and in 7 specific portions
(F1 to F7 from the proximal to the distal end) was determined by dual-energy
X-ray absorptiometry, and histomorphometry was also performed in proximal
tibial metaphysis. Ovariectomy (OVX) resulted in significant decreases in
the BMD in the whole femur and the F1, F2, F6 and F7 portions. Histomorphometrical
analysis of the tibia showed that the bone volume / tissue volume (BV/TV),
trabecular thickness (Tb.Th) and trabecular number (Tb.N) were decreased,
while trabecular separation (Tb.Sp) and osteoclast number / bone surface
(Oc.N/BS) were increased by OVX. The parameters for bone formation were
not changed by OVX. These data indicate that the bone loss within 2 weeks
is due to the enhancement of bone resorption. Vitamin K2 at 50
mg/kg inhibited the decrease in the BMD of the whole femur together with
the F6 and F7 portions. Vitamin K2 also inhibited the decrease
in Tb.N and the increases in Tb.Sp, Oc.N/BS and osteoclast surface / bone
surface (Oc.S/BS) caused by OVX. These results suggest that vitamin K2
prevents bone loss through the inhibition of bone resorption and osteoclast
formation in vivo.
Keywords: Vitamin K2, Ovariectomy, Bone mineral density, Histomorphometry,
Osteoclast number