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Title: Vitamin K-dependent carboxylation of osteocalcin: friend or foe?

Author
item GUNDBERG, CAREN - Yale School Of Medicine
item LIAN, JANE - University Of Massachusetts
item BOOTH, SARAH - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: Advances in Nutrition
Publication Type: Review Article
Publication Acceptance Date: 2/15/2012
Publication Date: 3/1/2012
Citation: Gundberg, C.M., Lian, J.B., Booth, S.L. 2012. Vitamin K-dependent carboxylation of osteocalcin: friend or foe?. Advances in Nutrition. 3:149-157.

Interpretive Summary:

Technical Abstract: Osteocalcin originates from osteooblastic synthesis and is deposited into bone or released into circulation, where it correlates with histological measures of bone formation. The presence of three vitamin K-dependent gamma-carboxyglutamic acid (Gla) residues is critical for osteocalcin’s structure, which appears to regulate the maturation of bone mineral. In humans, the percentage of the circulating osteocalcin that is not gamma-carboxylated (percent ucOC) is used as a biomarker of vitamin K status. In contrast, when ucOC is not corrected for total osteocalcin, the interpretation of this measure is confounded by osteoblastic activity, independent of vitamin K. Observational studies using percent ucOC have led to the conclusion that vitamin K insufficiency leads to age-related bone loss. However clinical trials do not provide overall support for the suggestion that vitamin K supplementation of the general population will reduce bone loss or fracture risk. More recently, results from in vitro and in vivo studies using animal models indicate that ucOC is an active hormone with a positive role in glucose metabolism. By inference, vitamin K, which decreases ucOC, would have a detrimental effect. However, in humans this hypothesis is not supported by the limited data available nor is it supported by what has been established regarding osteocalcin chemistry. In summary, the specific function of osteocalcin in bone and glucose metabolism has yet to be elucidated.