Elsevier

Advances in Nutrition

Volume 3, Issue 2, March 2012, Pages 149-157
Advances in Nutrition

Vitamin K-Dependent Carboxylation of Osteocalcin: Friend or Foe?

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ABSTRACT

Osteocalcin originates from osteoblastic synthesis and is deposited into bone or released into circulation, where it correlates with histological measures of bone formation. The presence of 3 vitamin K-dependent γ carboxyglutamic acid 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 γ-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.

Abbreviations used

BMD
bone mineral density
Gla
γ carboxyglutamic acid
Glu
glutamic acid
HAP
hydroxyapatite
MK
menaquinone
RCT
randomized, double-masked, controlled clinical trial
ucOC
undercarboxylated osteocalcin

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Supported by the USDA Agricultural Research Service under Cooperative Agreement no. 58-1950-7-707 (S.L.B.) and NIH AR38460 and P30 DK04735 (C.M.G.) and 5R37DE012528 (J.B.L.). Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the authors and do not necessarily reflect the view of the USDA.

Author disclosures: C. M. Gundberg, J. B. Lian, and S. L. Booth, no conflicts of interest.