Vitamin K in the Treatment and Prevention of Osteoporosis and Arterial Calcification

Jamie Adams; Joseph Pepping


Am J Health Syst Pharm. 2005;62(15):1574-1581. 

In This Article

Abstract and Introduction


Purpose: The role of vitamin K in the prevention and treatment of osteoporosis and arterial calcification is examined.
Summary: Vitamin K is essential for the activation of vitamin K-dependent proteins, which are involved not only in blood coagulation but in bone metabolism and the inhibition of arterial calcification. In humans, vitamin K is primarily a cofactor in the enzymatic reaction that converts glutamate residues into γ-carboxyglutamate residues in vitamin K-dependent proteins. Numerous studies have demonstrated the importance of vitamin K in bone health. The results of recent studies have suggested that concurrent use of menaquinone and vitamin D may substantially reduce bone loss. Menaquinone was also found to have a synergistic effect when administered with hormone therapy. Several epidemiologic and intervention studies have found that vitamin K deficiency causes reductions in bone mineral density and increases the risk of fractures. Arterial calcification is an active, cell-controlled process that shares many similarities with bone metabolism. Concurrent arterial calcification and osteoporosis have been called the "calcification paradox" and occur frequently in postmenopausal women. The results of two dose-response studies have indicated that the amount of vitamin K needed for optimal γ-carboxylation of osteocalcin is significantly higher than what is provided through diet alone and that current dosage recommendations should be increased to optimize bone mineralization. Few adverse effects have been reported from oral vitamin K.
Conclusion: Phytonadione and menaquinone may be effective for the prevention and treatment of osteoporosis and arterial calcification.


Osteoporosis and arterial calcification are major health concerns in modern societies. It is estimated that 30% of postmenopausal Caucasian women in the United States have osteoporosis and 54% have osteopenia[1,2] and 75-95% of men and women have some degree of coronary artery calcification on autopsy.[3,4] Although osteoporosis and arterial calcification were once thought to be unrelated conditions, recent studies suggest there may be a connection.[5,6,7,8] It appears that a common factor in the development of these two disorders may be vitamin K deficiency.

Over the past 20 years, several vitamin K-dependent (VKD) proteins have been discovered. Recent studies have shown that, in addition to their role in carboxylating coagulation factors, VKD proteins are involved in bone metabolism and the inhibition of arterial calcification. The two VKD proteins examined in this review are osteocalcin and matrix Gla protein (MGP). Osteocalcin appears to play a key role in bone metabolism but its mechanism of action has not been fully elucidated.[1] Osteocalcin is synthesized mainly by osteoblasts and, when carboxylated, has molecular properties that allow it to tightly bind hydroxyapatite in bone, thereby promoting mineralization.[9,10,11] Vitamin K is thought to promote bone mineralization by enhancing the carboxylation of osteocalcin.[10,12,13]

MGP is synthesized primarily by chondrocytes and vascular smooth muscle cells.[14,15,16,17] Recent animal studies have shown that MGP plays a key role in the inhibition of tissue calcification.[14,18] As with all VKD proteins, MGP must be carboxylated to function properly.[16,19]


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