Vitamin K and Osteoporosis

Abstract

Vitamin K acts as a coenzyme of carboxylase, catalyzing the carboxylation of several vitamin K dependent proteins. Beyond its well-known effects on blood coagulation, it also exerts relevant effects on bone and the vascular system. In this review, we point out the relevance of an adequate vitamin K intake to obtain sufficient levels of carboxylated (active form) vitamin K dependent proteins (such as Osteocalcin and matrix Gla protein) to prevent bone health. Another bone-related action of Vitamin K is being a ligand of the nuclear steroid and xenobiotic receptor (SXR). We also discuss the recommended intake, deficiency, and assessment of vitamin K. Furthermore, we review the few available studies that have as pre-specified outcome bone fractures, indicating that we need more clinical studies to confirm that vitamin K is a potential therapeutic agent for bone fractures.

Keywords: Osteocalcin; bone fractures; matrix Gla protein; vitamin K; vitamin K deficiency; vitamin K levels; vitamin K-dependent proteins.

Figure 1

Effects of vitamin K on activity of osteoblasts and osteoclasts. Bone cell function is modulated by both vitamin k dependent carboxylated proteins (c-MGP and c-OC) and vitamin K directly (gamma-carboxylation independent effects). Vitamin K (VK) plays a considerable role in maintaining bone strength since it regulates bone remodeling by promoting the osteoblast-to-osteocyte transition and by limiting osteoclastogenesis. This effect would take place mainly through the VK-dependent activation of bone Gla-proteins: Osteocalcin (OC) and matrix Gla protein (MGP protein). OC secreted by osteoblasts, plays an essential role in the synthesis and regulation of bone matrix. The undercarboxylated OC, shows a reduced calcium and hydroxyapatite binding activity, while, the active carboxylated (cOC) form is mainly involved in bone mineralization as it allows the interaction between its calcium-binding Gla residues with the calcium ions of hydroxyapatite: the main mechanism that enables OC to contribute to the formation of hydroxyapatite crystals. Oc acts also as an inhibitor of bone mineralization thus regulating the rate of mineral maturation (see also the text for the details).