Inhibitory Effect of Vitamin K2 (Menatetrenone) on Bone Resorption in Ovariectomized Rats: A Histomorphometric and Dual Energy X-Ray Absorptiometric Study

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.

Effects of the combination of vitamin K and teriparatide on the bone metabolism in ovariectomized rats

“…Similarly, VK modulated Ob.S/BS and Oc.S/BS in the histomorphometric parameters. Although these changes were small, the present results suggest that VK increases the bone formation but suppresses the bone degradation in an osteoporosis model, as previously reported for the effect of VK (7,8,24,25). Of note, VK administration significantly decreases Glu-OC but increases Gla-OC in sera, possibly by acting on the OC metabolism.…”

“…Previously, it has been reported that VK binds to the steroid and xenobiotic receptor and modulates the gene transcription in human osteoblastic cells (5,6). Additionally, VK plays roles not only in enhancing bone formation, but also in suppressing bone degradation (7,8). Clinically, VK has been shown to prevent bone loss and fractures in postmenopausal females with osteoporosis (9)(10)(11)(12).…”

Curative Effect of Combined Treatment With Alendronate and 1 α-Hydroxyvitamin D3 on Bone Loss by Ovariectomy in Aged Rats

“…All cancellous bone tissue between the traced lines was measured, with the exception of a ±0.3-mm-thick transitional zone lying between the cortical and cancellous bone tissue. The following parameters were measured as described before (48,49). The static parameters: trabecular bone volume /tissue volume (BV /TV, %), trabecular thickness (Tb.Th, mm), and trabecular number (Tb.N, / mm).…”

Menatetrenone Ameliorates Reduction in Bone Mineral Density and Bone Strength in Sciatic Neurectomized Rats

“…Recent clinical studies have suggested that MK-4 effectively prevents the occurrence of new frac tures in patients with postmenopausal osteoporosis (6 -8) and ameliorates osteoporosis associated with Parkin son's disease (9). The effects of MK-4 on bone metabo lism were demonstrated in a model of postmenopausal osteoporosis (10)(11)(12). It is generally accepted that bone resorption is increased in ovariectomized rats.…”

“…It is generally accepted that bone resorption is increased in ovariectomized rats. Various studies have suggested that MK-4 prevents, to some extent, the bone loss induced by ovariectomy by inhibit ing bone resorption (10,11). We reported that MK-4 protected against the loss of trabecular bone volume and its structure in rats rendered osteoporosic by sciatic neurectomy, through the process of maintaining bone formation (13 Three weeks after neurectomy, six neurectomized rats (SNx) and six sham-operated rats were sacrificed to obtain pre-administration data (day 21).…”