Effects of Vitamin K2 on the Development of Osteopenia in Rats as the Models of Osteoporosis

Abstract

Vitamin K2 is widely used for the treatment of osteoporosis in Japan. To understand the effects of vitamin K2 on bone mass and bone metabolism, we reviewed its effects on the development of osteopenia in rats, which characterizes models of osteoporosis. Vitamin K2 was found to attenuate the increase in bone resorption and/or maintain bone formation, reduce bone loss, protect against the loss of trabecular bone mass and its connectivity, and prevent the decrease in strength of the long bone in ovariectomized rats. However, combined treatment of bisphosphonates and vitamin K2 had an additive effect in preventing the deterioration of the trabecular bone architecture in ovariectomized rats, while the combined treatment of raloxifene and vitamin K2 improved the bone strength of the femoral neck. The use of vitamin K2 alone suppressed the increase in trabecular bone turnover and endocortical bone resorption, which attenuated the development of cancellous and cortical osteopenia in orchidectomized rats. In addition, vitamin K2 inhibited the decrease in bone formation in prednisolone-treated rats, thereby preventing cancellous and cortical osteopenia. In sciatic neurectomized rats, vitamin K2 suppressed endocortical bone resorption and stimulated bone formation, delaying the reduction of the trabecular thickness and retarding the development of cortical osteopenia. Vitamin K2 also prevented the acceleration of bone resorption and the reduction in bone formation in tail-suspended rats, which counteracted cancellous bone loss. Concomitant use of vitamin K2 with a bisphosphonate ameliorated the suppression of bone formation and more effectively prevented cancellous bone loss in tail-suspended rats. Vitamin K2 stimulated renal calcium reabsorption, retarded the increase in serum parathyroid hormone levels, and attenuated cortical bone loss primarily by suppressing bone resorption in calcium-deficient rats while maintaining the strength of the long bone in rats with magnesium deficiency. These findings suggest that vitamin K2 may not only stimulate bone formation, but may also suppress bone resorption. Thus, vitamin K2 could regulate bone metabolism in rats, which represented the various models of osteoporosis. However, the effects of vitamin K2 on bone mass and bone metabolism seem to be modest.

Bone quality and vitamin K2 in type 2 diabetes: Review of preclinical and clinical studies

“…It is known that vitamin K 2 , a commercially available agent for osteoporosis treatment in Asia, can prevent fractures in postmenopausal women, despite its modest effect on BMD, suggesting a probable effect of vitamin K 2 on bone quality 4,5 . This notion is supported by animal studies that have demonstrated that vitamin K 2 administration improves bone quality 5,6 …”

“…4,5 This notion is supported by animal studies that have demonstrated that vitamin K2 administration improves bone quality. 5,6 There are two naturally occurring forms of vitamin K, phylloquinone and menaquinones. All forms of vitamin K contain a 2-methyl-1,4-naphthoquinone ring as part of their structure, and individual forms differ in the length and degree of saturation of a variable aliphatic side chain attached at the 3-position ( Figure 1).…”

Vitamin K promotes mineralization, osteoblast-to-osteocyte transition, and an anticatabolic phenotype by γ-carboxylation-dependent and -independent mechanisms

“…Osteocytes appear to initiate bone repair in response to microcracks (12), as well as new bone formation in response to increased loading of bone (37,49). Vitamin K2 has also been proven effective in preventing bone loss in rat immobilization/disuse models (28,29). In both of these examples of pathological bone loss, there is evidence for a central role for osteocyte apoptosis, and it is therefore plausible that the action of vitamin K was at least partly at the level of the osteocyte.…”

Comparison of the Effect of Vitamin K2 and Risedronate on Trabecular Bone in Glucocorticoid-Treated Rats: A Bone Histomorphometry Study

“…A few studies showed the effects of combined treatment with bisphosphonates and vitamin K 2 in other models of osteoporosis. 28 - 31 Ito et al 29 demonstrated additive effect of risedronate and vitamin K 2 in preventing deterioration of the trabecular bone architecture in ovariectomized rats, whereas Otomo et al 30 showed no significant additive effect of risedronate and vitamin K 2 on bone turnover, bone mass/density, bone structure, mineral properties (mineral-to-matrix ratio), and bone strength evidenced by no significant effect of vitamin K 2 on bone parameters in ovariectomized rats. Furthermore, Iwasaki et al 31 reported that concomitant use of vitamin K 2 with incadronate ameliorated suppression of bone formation and more effectively prevented cancellous bone loss in tail-suspended rats.…”