Bone Abstracts

Vitamin K is a group name for a number of closely related compounds. Relevant structures for this presentation are phylloquinone (vitamin K1), menaquinone-4 (MK-4) and MK-7. The latter two are members of the vitamin K2 family. The function of all forms of vitamin K is to catalyze the formation of Gla-residues, which are strong calcium-binding groups and essential for the activity of the proteins in which they occur. For calcium metabolism three Gla-proteins are of particular interest: osteocalcin, matrix Gla-protein (MGP) and Gla-rich protein (GRP). Population-based studies have demonstrated that poor vitamin K status is associated with accelerated bone loss, low BMD and osteoporosis, but human vitamin K intervention studies have shown controversial outcomes. We have performed three independent vitamin K RCTs in postmenopausal women using vitamin K1, MK-4, or MK-7, and using DEXA BMD and BMC as a clinical endpoint. All three studies showed a positive effect of vitamin K and the effect of MK-7 was observed at a relatively low dose (180 μg/day). Besides its effect on bone, vitamin K has also a positive effect on vascular characteristics (elasticity and pulse-wave velocity). MGP, the main calcification inhibitor in the vasculature, is undercarboxylated in the healthy population suggesting subclinical vitamin K insufficiency. Calcium supplements may increase the vascular calcium load, which is consistent with reports in the literature claiming increased arterial calcification as a result of calcium supplements. Whereas osteocalcin is a direct marker for bone metabolism, uncarboxylated MGP is a marker for vascular calcification risk and mortality. We have designed an assay for circulating uncarboxylated MGP with which we have demonstrated a strong association between vascular vitamin K status and cardiovascular disease. The assay is now available in an automated form (IDS-iSYS inaKtiv MGP assay). The assay was found to be highly predictive for calcifications in chronic kidney disease and peripheral artery disease. We conclude that increased vitamin K intake helps protect against both postmenopausal bone loss and arterial calcification. In case calcium supplements (with or without vitamin D) are prescribed for the prevention of bone loss, it is recommended to combine this with vitamin K.