- Stenflo, J., Fernlund, P., Egan, W. & Roepstorff, P. Vitamin K dependent modifications of glutamic acid residues in prothrombin. Proc. Natl Acad. Sci. USA 71, 2730–2733 (1974).
Article CAS PubMed PubMed Central Google Scholar
- Suttie, J. W. The biochemical basis of warfarin therapy. Adv. Exp. Med. Biol. 214, 3–16 (1987).
CAS PubMed Google Scholar
- Hauschka, P. V., Lian, J. B. & Gallop, P. M. Direct identification of the calcium-binding amino acid, γ-carboxyglutamate, in mineralized tissue. Proc. Natl Acad. Sci. USA 72, 3925–3929 (1975).
Article CAS PubMed PubMed Central Google Scholar
- Price, P. A., Otsuka, A. A., Poser, J. W., Kristaponis, J. & Raman, N. Characterization of a γ-carboxyglutamic acid-containing protein from bone. Proc. Natl Acad. Sci. USA 73, 1447–1451 (1976).
Article CAS PubMed PubMed Central Google Scholar
- Lee, N. K. et al. Endocrine regulation of energy metabolism by the skeleton. Cell 130, 456–469 (2007).
Article CAS PubMed PubMed Central Google Scholar
- Ferron, M., Hinoi, E., Karsenty, G. & Ducy, P. Osteocalcin differentially regulates β cell and adipocyte gene expression and affects the development of metabolic diseases in wild-type mice. Proc. Natl Acad. Sci. USA 105, 5266–5270 (2008).
Article CAS PubMed PubMed Central Google Scholar
- Ferron, M. et al. Insulin signaling in osteoblasts integrates bone remodeling and energy metabolism. Cell 142, 296–308 (2010).
Article CAS PubMed PubMed Central Google Scholar
- Fulzele, K. et al. Insulin receptor signaling in osteoblasts regulates postnatal bone acquisition and body composition. Cell 142, 309–319 (2010).
Article CAS PubMed PubMed Central Google Scholar
- Rosen, C. J. & Motyl, K. J. No bones about it: insulin modulates skeletal remodeling. Cell 142, 198–200 (2010).
Article CAS PubMed Google Scholar
- Kumar, R. & Vella, A. Carbohydrate metabolism and the skeleton: picking a bone with the β-cell. J. Clin. Endocrinol. Metab. 96, 1269–1271 (2011).
Article CAS PubMed PubMed Central Google Scholar
- Motyl, K. J., McCabe, L. R. & Schwartz, A. V. Bone and glucose metabolism: a two-way street. Arch. Biochem. Biophys. 503, 2–10 (2010).
Article CAS PubMed PubMed Central Google Scholar
- Sullivan, T. R., Duque, G., Keech, A. C. & Herrmann, M. An old friend in a new light: the role of osteocalcin in energy metabolism. Cardiovasc. Ther. http://dx.doi.org/10.1111/j.1755-5922.2011.00300.x.
- Reid, I. R. Relationships between fat and bone. Osteoporos. Int. 19, 595–606 (2007).
Article PubMed Google Scholar
- Kawai, M., Devlin, M. J. & Rosen, C. J. Fat targets for skeletal health. Nat. Rev. Rheumatol. 5, 365–372 (2009).
Article PubMed PubMed Central Google Scholar
- Karsenty, G. & Ferron, M. The contribution of bone to whole-organism physiology. Nature 481, 314–320 (2012).
Article CAS PubMed PubMed Central Google Scholar
- Rosen, C. J. & Klibanski, A. Bone, fat, and body composition: evolving concepts in the pathogenesis of osteoporosis. Am. J. Med. 122, 409–414 (2009).
Article CAS PubMed Google Scholar
- Shearer, M. J., Fu, X. & Booth, S. L. Vitamin K nutrition, metabolism, and requirements: current concepts and future research. Adv. Nutr. 3, 182–195 (2012).
Article CAS PubMed PubMed Central Google Scholar
- Rishavy, M. A. & Berkner, K. L. Vitamin K oxygenation, glutamate carboxylation, and processivity: defining the three critical facets of catalysis by the vitamin K-dependent carboxylase. Adv. Nutr. 3, 135–148 (2012).
Article CAS PubMed PubMed Central Google Scholar
- Berkner, K. L. The vitamin K-dependent carboxylase. Annu. Rev. Nutr. 25, 127–149 (2005).
Article CAS PubMed Google Scholar
- Viegas, C. S. et al. Gla-rich protein (GRP), a new vitamin K-dependent protein identified from sturgeon cartilage and highly conserved in vertebrates. J. Biol. Chem. 283, 36655–36664 (2008).
Article CAS PubMed PubMed Central Google Scholar
- Proudfoot, D. & Shanahan, C. M. Molecular mechanisms mediating vascular calcification: role of matrix Gla protein. Nephrology (Carlton) 11, 455–461 (2006).
Article CAS Google Scholar
- Dowd, T. L., Rosen, J. F., Li, L. & Gundberg, C. M. The three-dimensional structure of bovine calcium ion-bound osteocalcin using 1H NMR spectroscopy. Biochemistry 42, 7769–7779 (2003).
Article CAS PubMed Google Scholar
- Hauschka, P. V. & Carr, S. A. Calcium-dependent α-helical structure in osteocalcin. Biochemistry 21, 2538–2547 (1982).
Article CAS PubMed Google Scholar
- Hoang, Q. Q., Sicheri, F., Howard, A. J. & Yang, D. S. Bone recognition mechanism of porcine osteocalcin from crystal structure. Nature 425, 977–980 (2003).
Article CAS PubMed Google Scholar
- Desbois, C., Hogue, D. A. & Karsenty, G. The mouse osteocalcin gene cluster contains three genes with two separate spatial and temporal patterns of expression. J. Biol. Chem. 269, 1183–1190 (1994).
CAS PubMed Google Scholar
- Kerner, S. A., Scott, R. A. & Pike, J. W. Sequence elements in the human osteocalcin gene confer basal activation and inducible response to hormonal vitamin D3 . Proc. Natl Acad. Sci. USA 86, 4455–4459 (1989).
Article CAS PubMed PubMed Central Google Scholar
- Lian, J. et al. Structure of the rat osteocalcin gene and regulation of vitamin D-dependent expression. Proc. Natl Acad. Sci. USA 86, 1143–1147 (1989).
Article CAS PubMed PubMed Central Google Scholar
- Boivin, G et al. Localization of endogenous osteocalcin in neonatal rat bone and its absence in articular cartilage: effect of warfarin treatment. Virchows Arch. A. Pathol. Anat. Histopathol. 417, 505–512 (1990).
Article CAS PubMed Google Scholar
- Price, P. A., Lothringer, J. W., Baukol, S. A. & Reddi, A. H. Developmental appearance of the vitamin K-dependent protein of bone during calcification. Analysis of mineralizing tissues in human, calf, and rat. J. Biol. Chem. 256, 3781–3784 (1981).
CAS PubMed Google Scholar
- Hauschka, P. V. & Reid, M. L. Timed appearance of a calcium-binding protein containing γ-carboxyglutamic acid in developing chick bone. Dev. Biol. 65, 426–434 (1978).
Article CAS PubMed Google Scholar
- Owen, T. A., et al. Progressive development of the rat osteoblast phenotype in vitro: reciprocal relationships in expression of genes associated with osteoblast proliferation and differentiation during formation of the bone extracellular matrix. J. Cell Physiol. 143, 420–430 (1990).
Article CAS PubMed Google Scholar
- Ducy, P. et al. Increased bone formation in osteocalcin-deficient mice. Nature 382, 448–452 (1996).
Article CAS PubMed Google Scholar
- Boskey, A. L. et al. Fourier transform infrared microspectroscopic analysis of bones of osteocalcin-deficient mice provides insight into the function of osteocalcin. Bone 23, 187–196 (1998).
Article CAS PubMed Google Scholar
- Poundarik, A., Gundberg, C. & Vashishth, D. Non-collageneous proteins influence bone mineral size, shape and orientation: a SAXS study. J. Bone Miner. Res. 26 (Suppl.), S36 (2011).
Google Scholar
- Fratzl, P., Paris, O., Klaushofer, K. & Landis, W. J. Bone mineralization in an osteogenesis imperfecta mouse model studied by small-angle X-ray scattering. J. Clin. Invest. 97, 396–402 (1996).
Article CAS PubMed PubMed Central Google Scholar
- Brown, J. P., Delmas, P. D., Arlot, M. & Meunier, P. J. Active bone turnover of the cortico-endosteal envelope in postmenopausal osteoporosis. J. Clin. Endocrinol. Metab. 64, 954–959 (1987).
Article CAS PubMed Google Scholar
- Brown, J. P. et al. Serum bone Gla-protein: a specific marker for bone formation in postmenopausal osteoporosis. Lancet 1, 1091–1093 (1984).
Article CAS PubMed Google Scholar
- Eastell, R. et al. Bone formation rate in older normal women: concurrent assessment with bone histomorphometry, calcium kinetics, and biochemical markers. J. Clin. Endocrinol. Metab. 67, 741–748 (1988).
Article CAS PubMed Google Scholar
- Price, P. A., Williamson, M. K. & Lothringer, J. W. Origin of the vitamin K-dependent bone protein found in plasma and its clearance by kidney and bone. J. Biol. Chem. 256, 12760–12766 (1981).
CAS PubMed Google Scholar
- Garnero, P. et al. Measurement of serum osteocalcin with a human-specific two-site immunoradiometric assay. J. Bone Miner. Res. 7, 1389–1398 (1992).
Article CAS PubMed Google Scholar
- Ivaska, K. K. et al. Release of intact and fragmented osteocalcin molecules from bone matrix during bone resorption in vitro. J. Biol. Chem. 279, 18361–18369 (2004).
Article CAS PubMed Google Scholar
- Gundberg, C. M. & Weinstein, R. S. Multiple immunoreactive forms of osteocalcin in uremic serum. J. Clin. Invest. 77, 1762–1767 (1986).
Article CAS PubMed PubMed Central Google Scholar
- Taylor, A. K. et al. Multiple osteocalcin fragments in human urine and serum as detected by a midmolecule osteocalcin radioimmunoassay. J. Clin. Endocrinol. Metab. 70, 467–472 (1990).
Article CAS PubMed Google Scholar
- Ivaska, K. K. et al. Urinary osteocalcin as a marker of bone metabolism. Clin. Chem. 51, 618–628 (2005).
Article CAS PubMed Google Scholar
- Eastell, R. & Hannon, R. A. Biomarkers of bone health and osteoporosis risk. Proc. Nutr. Soc. 67, 157–162 (2008).
Article PubMed Google Scholar
- Looker, A. C. et al. Clinical use of biochemical markers of bone remodeling: current status and future directions. Osteoporos. Int. 11, 467–480 (2000).
Article CAS PubMed Google Scholar
- Price, P. A. & Williamson, M. K. Effects of warfarin on bone. Studies on the vitamin K-dependent protein of rat bone. J. Biol. Chem. 256, 12754–12759 (1981).
CAS PubMed Google Scholar
- Benton, M. E., Price, P. A. & Suttie, J. W. Multi-site-specificity of the vitamin K-dependent carboxylase: in vitro carboxylation of des-γ-carboxylated bone Gla protein and des-γ-carboxylated pro bone Gla protein. Biochemistry 34, 9541–9551 (1995).
Article CAS PubMed Google Scholar
- Cairns, J. R. & Price, P. A. Direct demonstration that the vitamin K-dependent bone Gla protein is incompletely γ-carboxylated in humans. J. Bone Miner. Res. 9, 1989–1997 (1994).
Article CAS PubMed Google Scholar
- Booth, S. L. & Al Rajabi, A. Determinants of vitamin K status in humans. Vitam. Horm. 78, 1–22 (2008).
Article CAS PubMed Google Scholar
- Food and Nutrition Board & Institute of Medicine. Dietary Reference Intakes for Vitamin A, vitamin K, Arsenic Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. (National Academy Press, Washington DC, 2001).
- Suttie, J. W. The importance of menaquinones in human nutrition. Annu. Rev. Nutr. 15, 399–417 (1995).
Article CAS PubMed Google Scholar
- Booth, S. L. et al. Dietary phylloquinone depletion and repletion in older women. J. Nutr. 133, 2565–2569 (2003).
Article CAS PubMed Google Scholar
- Truong, J. T. et al. Age group and sex do not influence responses of vitamin K biomarkers to changes in dietary vitamin K. J. Nutr. 142, 936–941 (2012).
Article CAS PubMed PubMed Central Google Scholar
- Booth, S. L. et al. Effect of vitamin K supplementation on bone loss in elderly men and women. J. Clin. Endocrinol. Metab. 93, 1217–1223 (2008).
Article CAS PubMed PubMed Central Google Scholar
- Binkley, N. et al. Vitamin K treatment reduces undercarboxylated osteocalcin but does not alter bone turnover, density, or geometry in healthy postmenopausal North American women. J. Bone Miner. Res. 24, 983–991 (2009).
Article CAS PubMed Google Scholar
- Cheung, A. M. et al. Vitamin K supplementation in postmenopausal women with osteopenia (ECKO trial): a randomized controlled trial. PLoS Med. 5, e196 (2008).
Article CAS PubMed Google Scholar
- Binkley, N. C., Krueger, D. C., Engelke, J. A., Foley, A. L. & Suttie, J. W. Vitamin K supplementation reduces serum concentrations of under-γ-carboxylated osteocalcin in healthy young and elderly adults. Am. J. Clin. Nutr. 72, 1523–1528 (2000).
Article CAS PubMed Google Scholar
- Bolton-Smith, C. et al. Two-year randomized controlled trial of vitamin K1 (phylloquinone) and vitamin D3 plus calcium on the bone health of older women. J. Bone Miner. Res. 22, 509–519 (2007).
Article CAS PubMed Google Scholar
- van Summeren, M. J. et al. The effect of menaquinone-7 (vitamin K2) supplementation on osteocalcin carboxylation in healthy prepubertal children. Br. J. Nutr. 102, 1171–1178 (2009).
Article CAS PubMed Google Scholar
- Gundberg, C. M., Lian, J. B. & Booth, S. L. Vitamin K-dependent carboxylation of osteocalcin: friend or foe? Adv. Nutr. 3, 149–157 (2012).
Article CAS PubMed PubMed Central Google Scholar
- Gundberg, C. M., Nieman, S. D., Abrams, S. & Rosen, H. Vitamin K status and bone health: an analysis of methods for determination of undercarboxylated osteocalcin. J. Clin. Endocrinol. Metab. 83, 3258–3266 (1998).
CAS PubMed Google Scholar
- Adami, S. Bone health in diabetes: considerations for clinical management. Curr. Med. Res. Opin. 25, 1057–1072 (2009).
Article PubMed Google Scholar
- Schwartz, A. V. et al. Older women with diabetes have an increased risk of fracture: a prospective study. J. Clin. Endocrinol. Metab. 86, 32–38 (2001).
Article CAS PubMed Google Scholar
- Vestergaard, P., Rejnmark, L. & Mosekilde, L. Relative fracture risk in patients with diabetes mellitus, and the impact of insulin and oral antidiabetic medication on relative fracture risk. Diabetologia 48, 1292–1299 (2005).
Article CAS PubMed Google Scholar
- Bonds, D. E. et al. Risk of fracture in women with type 2 diabetes: the Women's Health Initiative Observational Study. J. Clin. Endocrinol. Metab. 91, 3404–3410 (2006).
Article CAS PubMed Google Scholar
- Vestergaard, P. Discrepancies in bone mineral density and fracture risk in patients with type 1 and type 2 diabetes—a meta-analysis. Osteoporos. Int. 18, 427–444 (2007).
Article CAS PubMed Google Scholar
- Schwartz, A. V. et al. Intensive glycemic control is not associated with fractures or falls in the ACCORD randomized trial. Diabetes Care 35, 1525–1531 (2012).
Article PubMed PubMed Central Google Scholar
- Takada, I. et al. A histone lysine methyltransferase activated by non-canonical Wnt signalling suppresses PPAR-γ transactivation. Nat. Cell Biol. 9, 1273–1285 (2007).
Article CAS PubMed Google Scholar
- Gimble, J. M. & Nuttall, M. E. The relationship between adipose tissue and bone metabolism. Clin. Biochem. 45, 874–879 (2012).
Article CAS PubMed Google Scholar
- Griffith, J. F. et al. Vertebral bone mineral density, marrow perfusion, and fat content in healthy men and men with osteoporosis: dynamic contrast-enhanced MR imaging and MR spectroscopy. Radiology 236, 945–951 (2005).
Article PubMed Google Scholar
- Ducy, P. et al. Leptin inhibits bone formation through a hypothalamic relay: a central control of bone mass. Cell 100, 197–207 (2000).
Article CAS PubMed Google Scholar
- Elefteriou, F. Regulation of bone remodeling by the central and peripheral nervous system. Arch. Biochem. Biophys. 473, 231–236 (2008).
Article CAS PubMed PubMed Central Google Scholar
- Hinoi, E. et al. The sympathetic tone mediates leptin's inhibition of insulin secretion by modulating osteocalcin bioactivity. J. Cell Biol. 183, 1235–1242 (2008).
Article CAS PubMed PubMed Central Google Scholar
- Yip, S. C., Saha, S. & Chernoff, J. PTP1B: a double agent in metabolism and oncogenesis. Trends Biochem. Sci. 35, 442–449 (2010).
Article CAS PubMed PubMed Central Google Scholar
- Zee, T., Settembre, C., Levine, R. L. & Karsenty, G. T-cell protein tyrosine phosphatase regulates bone resorption and whole-body insulin sensitivity through its expression in osteoblasts. Mol. Cell Biol. 32, 1080–1088 (2012).
Article CAS PubMed PubMed Central Google Scholar
- Poser, J. W. & Price, P. A. A method for decarboxylation of γ-carboxyglutamic acid in proteins. Properties of the decarboxylated γ-carboxyglutamic acid protein from calf bone. J. Biol. Chem. 254, 431–436 (1979).
CAS PubMed Google Scholar
- Kumm, J., Ivaska, K. K., Rohtla, K., Vaananen, K. & Tamm, A. Urinary osteocalcin and other markers of bone metabolism: the effect of risedronate therapy. Scand. J. Clin. Lab. Invest. 68, 459–463 (2008).
Article CAS PubMed Google Scholar
- Oury, F. et al. Endocrine regulation of male fertility by the skeleton. Cell 144, 796–809 (2011).
Article CAS PubMed PubMed Central Google Scholar
- Wellendorph, P. et al. Deorphanization of GPRC6A: a promiscuous L-α-amino acid receptor with preference for basic amino acids. Mol. Pharmacol. 67, 589–597 (2005).
Article CAS PubMed Google Scholar
- Wellendorph, P. & Bräuner-Osborne, H. Molecular cloning, expression, and sequence analysis of GPRC6A, a novel family C G-protein-coupled receptor. Gene 335, 37–46 (2004).
Article CAS PubMed Google Scholar
- Pi, M., Garner, S. C., Flannery, P., Spurney, R. F. & Quarles, L. D. Sensing of extracellular cations in CasR-deficient osteoblasts. Evidence for a novel cation-sensing mechanism. J. Biol. Chem. 275, 3256–3263 (2000).
Article CAS PubMed Google Scholar
- Wellendorph, P. et al. No evidence for a bone phenotype in GPRC6A knockout mice under normal physiological conditions. J. Mol. Endocrinol. 42, 215–223 (2009).
Article CAS PubMed Google Scholar
- Pi, M. et al. GPRC6A null mice exhibit osteopenia, feminization and metabolic syndrome. PLoS ONE 3, e3858 (2008).
Article CAS PubMed PubMed Central Google Scholar
- Urakawa, I. et al. Klotho converts canonical FGF receptor into a specific receptor for FGF23. Nature 444, 770–774 (2006).
Article CAS PubMed Google Scholar
- Krakauer, J.C. et al. Bone loss and bone turnover in diabetes. Diabetes 44, 775–782 (1995).
Article CAS PubMed Google Scholar
- Pater, A., Sypniewska, G. & Pilecki, O. Biochemical markers of bone cell activity in children with type 1 diabetes mellitus. J. Pediatr. Endocrinol. Metab. 23, 81–86 (2010).
Article CAS PubMed Google Scholar
- Gerdhem, P., Isaksson, A., Akesson, K. & Obrant, K. J. Increased bone density and decreased bone turnover, but no evident alteration of fracture susceptibility in elderly women with diabetes mellitus. Osteoporos. Int. 16, 1506–1512 (2005).
Article CAS PubMed Google Scholar
- Rosato, M. T., Schneider, S. H. & Shapses, S. A. Bone turnover and insulin-like growth factor I levels increase after improved glycemic control in noninsulin-dependent diabetes mellitus. Calcif. Tissue Int. 63, 107–111 (1998).
Article CAS PubMed Google Scholar
- Bao, Y. Q. et al. Relationship between serum osteocalcin and glycaemic variability in type 2 diabetes. Clin. Exp. Pharmacol. Physiol. 38, 50–54 (2011).
Article CAS PubMed Google Scholar
- Kanazawa, I. et al. Adiponectin is associated with changes in bone markers during glycemic control in type 2 diabetes mellitus. J. Clin. Endocrinol. Metab. 94, 3031–3037 (2009).
Article CAS PubMed Google Scholar
- Saleem, U., Mosley, T. H., Jr. & Kullo, I. J. Serum osteocalcin is associated with measures of insulin resistance, adipokine levels, and the presence of metabolic syndrome. Arterioscler. Thromb. Vasc Biol. 30, 1474–1478 (2010).
Article CAS PubMed PubMed Central Google Scholar
- Pittas, A. G., Harris, S. S., Eliades, M., Stark, P. & Dawson-Hughes, B. Association between serum osteocalcin and markers of metabolic phenotype. J. Clin. Endocrinol. Metab. 94, 827–832 (2009).
Article CAS PubMed Google Scholar
- Shea, M. K. et al. γ-Carboxylation of osteocalcin and insulin resistance in older men and women. Am. J. Clin. Nutr. 90, 1230–1235 (2009).
Article CAS PubMed PubMed Central Google Scholar
- Hwang, Y. C., Jeong, I. K., Ahn, K. J. & Chung, H. Y. The uncarboxylated form of osteocalcin is associated with improved glucose tolerance and enhanced β-cell function in middle-aged male subjects. Diabetes Metab. Res. Rev. 25, 768–772 (2009).
Article CAS PubMed Google Scholar
- Foresta, C. et al. Evidence for osteocalcin production by adipose tissue and its role in human metabolism. J. Clin. Endocrinol. Metab. 95, 3502–3506 (2010).
Article CAS PubMed Google Scholar
- Shea, M. K. et al. Adulthood obesity is positively associated with adipose tissue concentrations of vitamin K and inversely associated with circulating indicators of vitamin K status in men and women. J. Nutr. 140, 1029–1034 (2010).
Article CAS PubMed PubMed Central Google Scholar
- Pitroda, A. P., Harris, S. S. & Dawson-Hughes, B. The association of adiposity with parathyroid hormone in healthy older adults. Endocrine 36, 218–223 (2009).
Article CAS PubMed PubMed Central Google Scholar
- Iki, M. et al. Serum undercarboxylated osteocalcin levels are inversely associated with glycemic status and insulin resistance in an elderly Japanese male population: Fujiwara-kyo Osteoporosis Risk in Men (FORMEN) Study. Osteoporos Int. 23, 761–770 (2012).
Article CAS PubMed Google Scholar
- Gravenstein, K. S. et al. Cross-sectional evidence of a signaling pathway from bone homeostasis to glucose metabolism. J. Clin. Endocrinol. Metab. 96, E884–E890 (2011).
Article CAS PubMed PubMed Central Google Scholar
- Boucher-Berry, C. et al. Vitamin D, osteocalcin and risk for adiposity as comorbidities in middle school children. J. Bone Miner. Res. 27, 283–293 (2012).
Article CAS PubMed Google Scholar
- Misra, M. et al. Relationships between serum adipokines, insulin levels, and bone density in girls with anorexia nervosa. J. Clin. Endocrinol. Metab. 92, 2046–2052 (2007).
Article CAS PubMed Google Scholar
- Pollock, N. K. et al. Lower uncarboxylated osteocalcin concentrations in children with prediabetes is associated with β-cell function. J. Clin. Endocrinol. Metab. 96, E1092–E1099 (2011).
Article PubMed PubMed Central Google Scholar
- Iglesias, P. et al. Serum concentrations of osteocalcin, procollagen type 1 N-terminal propeptide and β-CrossLaps in obese subjects with varying degrees of glucose tolerance. Clin. Endocrinol. 75, 184–188 (2011).
Article CAS Google Scholar
- Fernández-Real, J. M. et al. The relationship of serum osteocalcin concentration to insulin secretion, sensitivity, and disposal with hypocaloric diet and resistance training. J. Clin. Endocrinol. Metab. 94, 237–245 (2009).
Article CAS PubMed Google Scholar
- Bulló, M., Moreno-Navarrete, J. M., Fernández-Real, J. M. & Salas-Salvadó, J. Total and undercarboxylated osteocalcin predict changes in insulin sensitivity and β cell function in elderly men at high cardiovascular risk. Am. J. Clin. Nutr. 95, 249–255 (2012).
Article CAS PubMed Google Scholar
- Schwartz, A. V. et al. Undercarboxylated osteocalcin does not predict development of diabetes in older adults in the Health, Aging and Body Composition Study. J. Bone Miner. Res. 26 (Suppl.) 69 (2011).
Google Scholar
- Lihn, A. S., Pedersen, S. B. & Richelsen, B. Adiponectin: action, regulation and association to insulin sensitivity. Obes. Rev. 6, 13–21 (2005).
Article CAS PubMed Google Scholar
- Shi, Y. et al. Dissociation of the neuronal regulation of bone mass and energy metabolism by leptin in vivo. Proc. Natl Acad. Sci. USA 105, 20529–20533 (2008).
Article CAS PubMed PubMed Central Google Scholar
- Lee, Y. J. et al. Serum osteocalcin is inversely associated with adipocyte-specific fatty acid-binding protein in the Korean metabolic syndrome research initiatives. Diabetes Care 33, e90 (2010).
Article PubMed Google Scholar
- Hamann, C. et al. Delayed bone regeneration and low bone mass in a rat model of insulin-resistant type 2 diabetes mellitus is due to impaired osteoblast function. Am. J. Physiol. Endocrinol. Metab. 301, E1220–E1228 (2011).
Article CAS PubMed Google Scholar
- Maugeri, D. et al. Alendronate reduces the daily consumption of insulin (DCI) in patients with senile type I diabetes and osteoporosis. Arch. Gerontol. Geriatr. 34, 117–122 (2002).
Article CAS PubMed Google Scholar
- Vestergaard, P. Risk of newly diagnosed type 2 diabetes is reduced in users of alendronate. Calcif. Tissue Int. 89, 265–270 (2011).
Article CAS PubMed Google Scholar
- Keegan, T. H. et al. Effect of alendronate on bone mineral density and biochemical markers of bone turnover in type 2 diabetic women: the fracture intervention trial. Diabetes Care 27, 1547–1553 (2004).
Article CAS PubMed Google Scholar
- Luckman, S. P. et al. Nitrogen-containing bisphosphonates inhibit the mevalonate pathway and prevent post-translational prenylation of GTP-binding proteins, including Ras. J. Bone Miner. Res. 13, 581–589 (1998).
Article CAS PubMed Google Scholar
- Gluck, O. & Maricic, M. Skeletal and nonskeletal effects of raloxifene. Curr. Osteoporos. Rep. 1, 123–128 (2003).
Article PubMed Google Scholar
- Schafer, A. L. et al. Change in undercarboxylated osteocalcin is associated with changes in body weight, fat mass, and adiponectin: parathyroid hormone1–84 or alendronate therapy in postmenopausal women with osteoporosis (the PaTH study). J. Clin. Endocrinol. Metab. 96, E1982–1989 (2011).
Article CAS PubMed PubMed Central Google Scholar
- Sokoll, L. J. et al. Changes in serum osteocalcin, plasma phylloquinone, and urinary γ-carboxyglutamic acid in response to altered intakes of dietary phylloquinone in human subjects. Am. J. Clin. Nutr. 65, 779–784 (1997).
Article CAS PubMed Google Scholar
- Yoshida, M., Booth, S. L., Meigs, J. B., Saltzman, E. & Jacques, P. F. Phylloquinone intake, insulin sensitivity, and glycemic status in men and women. Am. J. Clin. Nutr. 88, 210–215 (2008).
Article CAS PubMed Google Scholar
- Yoshida, M. et al. Effect of vitamin K supplementation on insulin resistance in older men and women. Diabetes Care 31, 2092–2096 (2008).
Article CAS PubMed PubMed Central Google Scholar
- Beulens, J. W. et al. Dietary phylloquinone and menaquinones intakes and risk of type 2 diabetes. Diabetes Care 33, 1699–1705 (2010).
Article CAS PubMed PubMed Central Google Scholar
- Erkkila, A. T. & Booth, S. L. Vitamin K intake and atherosclerosis. Curr. Opin. Lipidol. 19, 39–42 (2008).
Article CAS PubMed Google Scholar
- Carter, P., Gray, L. J., Troughton, J., Khunti, K. & Davies, M. J. Fruit and vegetable intake and incidence of type 2 diabetes mellitus: systematic review and meta-analysis. BMJ 341, c4229 (2010).
Article PubMed PubMed Central Google Scholar
- Sakamoto, N., Nishiike, T., Iguchi, H. & Sakamoto, K. Possible effects of one week vitamin K (menaquinone-4) tablets intake on glucose tolerance in healthy young male volunteers with different descarboxy prothrombin levels. Clin. Nutr. 19, 259–263 (2000).
Article CAS PubMed Google Scholar
- Choi, H. J. et al. Vitamin K2 supplementation improves insulin sensitivity via osteocalcin metabolism: a placebo-controlled trial. Diabetes Care 34, e147 (2011).
Article PubMed PubMed Central Google Scholar
- Knapen, M. H. et al. Association of vitamin K status with adiponectin and body composition in healthy subjects: uncarboxylated osteocalcin is not associated with fat mass and body weight. Br. J. Nutr. 108, 1017–1024 (2011).
Article CAS PubMed Google Scholar
- Kumar, R., Binkley, N. & Vella, A. Effect of phylloquinone supplementation on glucose homeostasis in humans. Am. J. Clin. Nutr. 92, 1528–1532 (2010).
Article CAS PubMed PubMed Central Google Scholar
- Booth, S. L. & Mayer, J. Warfarin use and fracture risk. Nutr. Rev. 58, 20–22 (2000).
Article CAS PubMed Google Scholar
- Cropp, J. S. & Bussey, H. I. A review of enzyme induction of warfarin metabolism with recommendations for patient management. Pharmacotherapy 17, 917–928 (1997).
CAS PubMed Google Scholar
- Mega, J. L. A new era for anticoagulation in atrial fibrillation. N. Engl. J. Med. 365, 1052–1054 (2011).
Article CAS PubMed Google Scholar
- Ferron, M., Wei, J., Yoshizawa, T., Ducy, P. & Karsenty, G. An ELISA-based method to quantify osteocalcin carboxylation in mice. Biochem. Biophys. Res. Commun. 397, 691–696 (2010).
Article CAS PubMed PubMed Central Google Scholar
- Hetzel, P. G., Glanzmann, R., Hasler, P. W., Ladewick, A. & Bührer, C. Coumarin embryopathy in an extremely low birth weight infant associated with neonatal hepatitis and ocular malformations. Eur. J. Pediatr. 165, 358–360 (2006).
Article PubMed Google Scholar
- Scheen, A. J. Drug interactions of clinical importance with antihyperglycaemic agents: an update. Drug Saf. 28, 601–631 (2005).
Article CAS PubMed Google Scholar
- Soon, D. et al. Effect of exenatide on the pharmacokinetics and pharmacodynamics of warfarin in healthy Asian men. J. Clin. Pharmacol. 46, 1179–1187 (2006).
Article CAS PubMed Google Scholar
- Thyfault, J. P. & Booth, F. W. Lack of regular physical exercise or too much inactivity. Curr. Opin. Clin. Nutr. Metab. Care 14, 374–378 (2011).
Article PubMed Google Scholar
- Levinger, I. et al. The effect of acute exercise on undercarboxylated osteocalcin in obese men. Osteoporos. Int. 22, 1621–1626 (2011).
Article CAS PubMed Google Scholar
- Fujimura, R. et al. Effect of resistance exercise training on bone formation and resorption in young male subjects assessed by biomarkers of bone metabolism. J. Bone Miner. Res. 12, 656–662 (1997).
Article CAS PubMed Google Scholar
- Yarasheski, K. E., Campbell, J. A. & Kohrt, W. M. Effect of resistance exercise and growth hormone on bone density in older men. Clin. Endocrinol. (Oxf.) 47, 223–229 (1997).
Article CAS Google Scholar
- Schroeder, E. T., Hawkins, S. A. & Jaque, S. V. Musculoskeletal adaptations to 16 weeks of eccentric progressive resistance training in young women. J. Strength Cond. Res. 18, 227–235 (2004).
Article PubMed Google Scholar
- Judge, J. O. et al. Home-based resistance training improves femoral bone mineral density in women on hormone therapy. Osteoporos. Int. 16, 1096–1108 (2005).
Article PubMed Google Scholar
- Adami, S. et al. Physical activity and bone turnover markers: a cross-sectional and a longitudinal study. Calcif. Tissue Int. 83, 388–392 (2008).
Article CAS PubMed Google Scholar
- Booth, S. L. et al. Relationships between dietary intakes and fasting plasma concentrations of fat-soluble vitamins in humans. J. Nutr. 127, 587–592 (1997).
Article CAS PubMed Google Scholar
- Rochefort, G. Y. et al. Osteocalcin—insulin relationship in obese children: a role for the skeleton in energy metabolism. Clin. Endocrinol. (Oxf.) 75, 265–270 (2011).
Article CAS Google Scholar
- Ashcroft, F. M. & Rorsman, P. Diabetes mellitus and the β cell: the last ten years. Cell 148, 1160–1171 (2012).
Article CAS PubMed PubMed Central Google Scholar
- Yoshikawa, Y. et al. Genetic evidence points to an osteocalcin-independent influence of osteoblasts on energy metabolism. J. Bone Miner. Res. 26, 2012–2025 (2011).
Article CAS PubMed Google Scholar
- Wei, W. et al. Fibroblast growth factor 21 promotes bone loss by potentiating the effects of peroxisome proliferator-activated receptor γ. Proc. Natl Acad. Sci. USA 109, 3143–3148 (2012).
Article CAS PubMed PubMed Central Google Scholar
- Clowes, J. A., Khosla, S. & Eastell, R. Potential role of pancreatic and enteric hormones in regulating bone turnover. J. Bone Miner. Res. 20, 1497–1506 (2005).
Article CAS PubMed Google Scholar
- US Department of Agriculture. USDA National Nutrient Database for Standard Reference, Release 24 [online], (2012).