Effect of vitamin K in bone metabolism and vascular calcification: A review of mechanisms of action and evidences

Abstract

Osteoporosis is a public health concern associated with an increased risk of bone fractures and vascular calcification. Vitamin K presents unique benefits on these issues, although understudied. The two main forms of vitamin K are phylloquinone (vitamin K₁) and menaquinone (vitamin K₂). In this study, it was especially investigated the action of vitamin K₂ in bones and vessels. Vitamin K₂ has shown to stimulate bone formation by promoting osteoblast differentiation and carboxylation of osteocalcin, and increasing alkaline phosphatase, insulin-like growth factor-1, growth differentiation factor-15, and stanniocalcin 2 levels. Furthermore, vitamin K₂ reduces the pro-apoptotic proteins Fas and Bax in osteoblasts, and decreases osteoclast differentiation by increasing osteoprotegerin and reducing the receptor activator of nuclear factor kappa-B ligand. In blood vessels, vitamin K₂ reduces the formation of hydroxyapatite, through the carboxylation of matrix Gla protein and Gla rich protein, inhibits the apoptosis of vascular smooth muscle cells, by increasing growth arrest-specific gene 6, and reduces the transdifferentiation of vascular smooth muscle cells to osteoblasts. The commonly used dosage of vitamin K₂ in human studies is 45 mg/day and its application can be an interesting strategy in benefitting bone and vascular health, especially to osteoporotic post-menopausal women.

Keywords: Menaquinone; cardiovascular disease; osteoporosis; postmenopause.