Vitamin K is a nutrient originally identified as an essential factor for blood coagulation. Accumulated evidence indicates that subclinical non-
hemostatic vitamin K deficiency in extrahepatic tissues, particularly in bone, exists widely in the otherwise healthy adult population. Both
vitamin K1 and K2 have been shown to exert protective effects against
osteoporosis. The new
biological functions of
vitamin K in bone are considered to be attributable, at least in part, to promotion of gamma-carboxylation of
glutamic acid residues in
vitamin K-dependent
proteins, which is shared by both
vitamins K1 and K2. A recent evidence of significant correlation between polymorphism of
gamma-glutamyl carboxylase gene and bone mineral density supports the role of gamma-carboxylation-dependent actions of
vitamin K. In contrast,
vitamin K2-specific,gamma-carboxylation-unrelated functions have recently attracted scientific attention. Recent findings of
vitamin K2-specific transactivation of
steroid and xenobiotic receptor (SXR/PXR) may lead to new research avenue. The impact of genotype of
apoE, a major
vitamin K transporter, on ostepporosis as well as
Alzheimer disease and
atherosclerosis, raises a question whether
vitamin K is involved in the pathogenesis of these diseases. Molecular bases of coagulation-unrelated pleiotropic actions of
vitamin K and its implications in bone health deserve further investigations.