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Vitamin K and bone health

Published online by Cambridge University Press:  07 March 2007

Susanne Bügel
Department of Human Nutrition, The Royal Veterinary and Agricultural University, Rolighedsvej 30, 1958 Frederiksberg C, Denmark
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Vitamin K, originally recognised as a factor required for normal blood coagulation, is now receiving more attention in relation to its role in bone metabolism. Vitamin K is a coenzyme for glutamate carboxylase, which mediates the conversion of glutamate to γ-carboxyglutamate (Gla). Gla residues attract Ca2+ and incorporate these ions into the hydroxyapatite crystals. There are at least three Gla proteins associated with bone tissue, of which osteocalcin is the most abundant and best known. Osteocalcin is the major non-collagenous protein incorporated in bone matrix during bone formation. However, approximately 30% of the newly-produced osteocalcin stays in the circulation where it may be used as an indicator of bone formation. Vitamin K deficiency results in an increase in undercarboxylated osteocalcin, a protein with low biological activity. Several studies have demonstrated that low dietary vitamin K intake is associated with low bone mineral density or increased fractures. Additionally, vitamin K supplementation has been shown to reduce undercarboxylated osteocalcin and improve the bone turnover profile. Some studies have indicated that high levels of undercarboxylated osteocalcin (as a result of low vitamin K intake?) are associated with low bone mineral density and increased hip fracture. The current dietary recommendation for vitamin K is 1 μ/kg body weight per d, based on saturation of the coagulation system. The daily dietary vitamin K intake is estimated to be in the range 124–375 μg/d in a European population. Thus, a deficiency based on the hepatic coagulation system would be unusual, but recent data suggest that the requirement in relation to bone health might be higher.

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Copyright © The Nutrition Society 2003


Binkley, NC, Krueger, DC, Engelke, JA, Foley, AL & Suttie, JW (2000) Vitamin K supplementation reduces serum concentrations of under-gamma-carboxylated osteocalcin in healthy young and elderly adults. American Journal of Clinical Nutrition 72, 15231528.CrossRefGoogle Scholar
Binkley, NC & Suttie, JW (1995) Vitamin K nutrition and osteoporosis. Journal of Nutrition 125, 18121821.Google ScholarPubMed
Booth, SL, Broe, KE, Gagnon, DR, Tucker, KL, Hannan, MT, McLean, RR, Dawson-Hughes, B, Wilson, PW, Cupples, LA & Kiel, DP (2003) Vitamin K intake and bone mineral density in women and men. American Journal of Clinical Nutrition 77, 512516.CrossRefGoogle ScholarPubMed
Booth, SL, O'Brien-Morse, ME, Dallal, GE, Davidson, KW Gundberg, CM (1999) Response of vitamin K status to different intakes and sources of phylloquinone-rich foods: comparison of younger and older adults. American Journal of Clinical Nutrition 70, 368377.CrossRefGoogle ScholarPubMed
Booth, SL, Sadowski, JA, Weihrauch, JL & Ferland, G (1993) Vitamin K1 (phylloquinone) content of foods: A provisional table. Journal of Food Composition and Analysis 6, 109120.CrossRefGoogle Scholar
Booth, SL & Suttie, JW (1998) Dietary intake and adequacy of vitamin K1. Journal of Nutrition 128, 785788.CrossRefGoogle Scholar
Booth, SL, Tucker, KL, Chen, H, Hannan, MT, Gagnon, DR, Cupples, LA, Wilson, PW, Ordovas, J, Schaefer, EJ, Dawson-Hughes, B & Kiel, DP (2000) Dietary vitamin K intakes are associated with hip fracture but not with bone mineral density in elderly men and women. American Journal of Clinical Nutrition 71, 12011208.Google Scholar
Braam, LA, Knapen, MH, Geusens, P, Brouns, F, Hamulyak, K, Gerichhausen, MJ & Vermeer, C (2003) Vitamin Kl supplementation retards bone loss in postmenopausal women between 50 and 60 years of age. Calcified Tissue International (In the Press)Google Scholar
Conly, JM & Stein, K (1992) The production of menaquinones (Vitamin K2) by intestinal bacteria and their role in maintaining coagulation homeostasis. Progress in Food and Nutrition Science 16, 307343.Google ScholarPubMed
Craciun, AM, Wolf, J, Knapen, MHJ, Brouns, F & Vermeer, C (1998) Improved bone metabolism in female elite athletes after vitamin K supplementation. International Journal of Sports Medicine 19, 479484.CrossRefGoogle ScholarPubMed
Davidson, RT, Foley, AL, Engelke, JA & Suttie, JW (1998) Conversion of dietary phylloquinone to tissue menaquinone-4 in rats is not dependent on gut bacteria. Journal of Nutrition 128, 220223.Google Scholar
Douglas, AS, Robins, SP, Hutchison, JD, Porter, RW, Stewart, A & Reid, DM (1995) Carboxylation of osteocalcin in post-menopausal osteoporotic women following vitamin K and D supplementation. Bone 17, 1520.CrossRefGoogle ScholarPubMed
Feskanich, D, Weber, P, Willett, WC, Rockett, H, Booth, SL & Colditz, GA (1999) Vitamin K intake and hip fractures in women: a prospective study. American Journal of Clinical Nutrition 69, 7479.CrossRefGoogle ScholarPubMed
Gijsbers, BL, Jie, KS & Vermeer, C (1996) Effect of food composition on vitamin K absorption in human volunteers. British Journal of Nutrition 76, 223229.CrossRefGoogle ScholarPubMed
Hart, JP, Shearer, MJ, Klenerman, L, Catterall, A, Reeve, J, Sambrook, PN, Dodds, RA, Bitensky, L & Chayen, J (1985) Electrochemical detection of depressed circulation levels of vitamin Kl in osteoporosis. Journal of Clinical Endocrinology and Metabolism 60, 12681269.CrossRefGoogle Scholar
Hodges, SJ, Akesson, K, Vergnaud, P, Obrant, K & Delmas, PD (1993) Circulating levels of vitamins Kl and K2 decreased in elderly women with hip fracture. Journal of Bone Mineral Research 8, 12411245.CrossRefGoogle Scholar
Hodges, SJ, Pilkington, MJ, Stamp, TC, Catterall, A, Shearer, MJ, Bitensky, L & Chayen, J (1991) Depressed levels of circulating menaquinones in patients with osteoporotic fractures of the spine and femoral neck. Bone 12, 387389.CrossRefGoogle ScholarPubMed
Jie, KS, Gijsberg, BL, Knapen, MH, Hamulyák, K, Frank, HL & Vermeer, C (1993) Effects of vitamin K and oral anticoagulants on urinary Ca excretion. British Journal of Haematology 83, 100104.CrossRefGoogle Scholar
Jie, KG, Bots, ML, Vermeer, C, Witteman, JC & Grobbee, DE (1996) Vitamin K status and bone mass in women with and without aortic atherosclerosis: a population-based study. Calcified Tissue International 59, 352356.CrossRefGoogle ScholarPubMed
Karsenty, G (1998) Genetics of skeletogenesis. Developmental Genetics 22, 301313.3.0.CO;2-A>CrossRefGoogle ScholarPubMed
Knapen, MHJ, Hamulyák, K & Vermeer, C (1989) The effect of vitamin K supplementation on circulating osteocalcin (bone GLA protein) and urinary calcium excretion. Annals of Internal Medicine 111, 10011005.CrossRefGoogle ScholarPubMed
Knapen, MHJ, Jie, KG, Hamulyak, K & Vermeer, C (1993) Vitamin K induced changes in markers for osteoblast activity and urinary calcium loss. Calcified Tissue International 53, 8185.CrossRefGoogle ScholarPubMed
Knapen, MHJ, Kruseman, ACN, Wouters, RSME & Vermeer, C (1998) Correlation of serum osteocalcin fractions with bone mineral density in women during the first 10 years after menopause. Calcified Tissue International 63, 375379.CrossRefGoogle ScholarPubMed
Koshihara, Y, Hoshi, K, Ishibashi, H & Shiraki, M (1996) Vitamin K2 promotes lalpha,25(OH)2 vitamin D3-induced mineralization in human periosteal osteoblasts. Calcified Tissue International 59, 466473.Google Scholar
Lian, JB, Stein, GS, Stewart, C, Puchacz, E, Mackowiak, S, Aronow, M, Von Deck, M & Shalhoub, V (1989) Osteocalcin: characterization and regulated expression of the rat gene. Connective Tissue Research 21, 6168.CrossRefGoogle ScholarPubMed
Lipsky, JJ (1994) Nutritional sources of vitamin K. Mayo Clinic Proceedings 69, 462466.CrossRefGoogle ScholarPubMed
Luo, G, Ducy, P, McKee, MD, Pinero, GJ, Loyer, E, Behringer, RR & Karsenty, G (1997) Spontaneous calcification of arteries and cartilage in mice lacking matrix GLA protein. Nature 386, 7881.CrossRefGoogle ScholarPubMed
McKeown, NM, Jacques, PF, Gundberg, CM, Peterson, JW, Tucker, KL, Kiel, DP, Wilson, PWF & Booth, SL (2002) Dietary and nondietary determinants of vitamin K biochemical measures in men and women. Journal of Nutrition 132, 13291334.Google ScholarPubMed
Matsunaga, S, Ito, H & Sakou, T (1999) The effect of vitamin K and D supplementation on ovariectomy-induced bone loss. Calcified Tissue International 65, 285289.CrossRefGoogle Scholar
Nordic Council of Ministers (1996) Nordiska Näringsrekommendationer 1996 (Nordic Nutrition Recommendations 1996). TemaNord 1996, p. 28. Copenhagen, Denmark: Nordic Council of Ministers.Google Scholar
Pettifor, JM & Benson, R (1975) Congenital malformations associated with the administration of oral anticoagulants during pregnancy. Journal of Pediatrics 86, 459462.Google ScholarPubMed
Plantalech, L, Guillaumont, M, Vergnaud, P, Leclerq, M & Delmas, PD (1991) Impairment of gamma carboxylation of circulating osteocalcin (bone GLA protein) in elderly women. Journal of Bone Mineral Research 11, 12111216.Google Scholar
Ronden, JE, Drittij-Reijnders, MJ, Vermeer, C & Thijssen, HH (1998 a) Intestinal flora is not an intermediate in the phylloquinone-menaquinone-4 conversion in the rat. Biochimica et Biophysica Acta 1379, 6975.CrossRefGoogle Scholar
Ronden, JE, Thijssen, HH & Vermeer, C (1998 b) Tissue distribution of K-vitamers under different nutritional regimens in the rat. Biochimica et Biophysica Acta 1379, 1622.CrossRefGoogle ScholarPubMed
Schaafsma, A, Muskiet, FA, Storm, H, Hofstede, GJ, Pakan, I & Van der Veer, E (2000) Vitamin D(3) and vitamin K(1) supplementation of Dutch postmenopausal women with normal and low bone mineral densities: effects on serum 25-hydroxyvitamin D and carboxylated osteocalcin. European Journal of Clinical Nutrition 54, 626631.CrossRefGoogle ScholarPubMed
Scholz-Ahrens, KE, Delling, G, Jungblut, PW, Kallweit, E & Barth, CA (1996) Effect of ovariectomy on bone histology and plasma parameters of bone metabolism in nulliparous and mulliparous sows. Zeitschrift für Ernahrungswissenschaft 35, 1321.CrossRefGoogle Scholar
Schoon, EJ, Muller, MC, Vermeer, C, Schurgers, LJ, Brummer, RJ & Stockbrugger, RW (2001) Low serum and bone vitamin K status in patients with longstanding Crohn's disease: another pathogenetic factor of osteoporosis in Crohn's disease? Gut 48, 473477.CrossRefGoogle ScholarPubMed
Schurgers, LJ, Geleijnse, JM, Grobbee, DE, Pols, HA, Hofman, A, Witteman, JCM & Vermeer, C (1999) Nutritional intake of vitamin Kl (phylloquinone) and K2 (menaquinone) in The Netherlands. Journal of Nutritional and Environmental Medicine 9, 115122.CrossRefGoogle Scholar
Shanahan, CM & Weissberg, PL (1998) Smooth muscle cell heterogeneity: Patterns of gene expression in vascular smooth muscle cells in vitro and in vivo. Arteriosclerosis Thrombosis and Vascular Biology 18, 333338.CrossRefGoogle ScholarPubMed
Shearer, MJ & Bolton-Smith, C (2000) The UK food data-base for vitamin K and why we need it. Food Chemistry 68, 213218.CrossRefGoogle Scholar
Sokoll, LJ, Booth, SL, O'Brien, ME, Davidson, KW, Tsaioun, KI & Sadowski, JA (1997) Changes in serum osteocalcin, plasma phylloquinone, and urinary gamma-carboxyglutamic acid in response to altered intakes of dietary phylloquinone in human subjects. American Journal of Clinical Nutrition 65, 779784.CrossRefGoogle ScholarPubMed
Suttie, JW (1992) Vitamin K and human nutrition. Journal of the American Dietetic Association 92, 585590.Google ScholarPubMed
Szulc, P, Chapuy, MC, Meunier, PJ & Delmas, PD (1993) Serum undercarboxylated osteocalcin is a marker of the risk of hip fracture in elderly women. Journal of Clinical Investigation 91, 17691774.CrossRefGoogle ScholarPubMed
Szulc, P, Chapuy, MC, Meunier, PJ & Delmas, PD (1996) Serum undercarboxylated osteocalcin is a marker of the risk of hip fracture: a three year follow-up study. Bone 18, 487488.CrossRefGoogle ScholarPubMed
Ushiroyama, T, Ikeda, A & Ueki, M (2002) Effect of continuous combined therapy with vitamin K(2) and vitamin D(3) on bone mineral density and coagulofibrinolysis function in post-menopausal women. Maturitas 41, 211221.CrossRefGoogle Scholar
Vermeer, C & Braam, L (2001) Role of K vitamins in the regulation of tissue calcification. Journal of Bone Mineral Metabolism 19, 201206.CrossRefGoogle ScholarPubMed
Vermeer, C, Gijsbers, BLMG, Craciun, AM, Groenen-Van Dooren, MMCL & Knapen, MHJ (1996) Effects of vitamin K on bone mass and bone metabolism. Journal of Nutrition 126, 1187S1191S.CrossRefGoogle Scholar
Vermeer, C, Jie, KS & Knapen, MH (1995) Role of vitamin K in bone metabolism. Annual Review of Nutrition 15, 122.CrossRefGoogle ScholarPubMed
Vermeer, C & Schurgers, J (2000) A comprehensive review of vitamin K and vitamin K antagonists. Blood Stasis and Thrombosis 14, 339353.Google ScholarPubMed
Weber, P (2001) Vitamin K and bone health. Nutrition 17, 880887.CrossRefGoogle ScholarPubMed
Yagami, K, Suh, JY, Enomoto-Iwamoto, M, Koyama, E, Abrams, WR, Shapiro, IM, Pacifici, M & Iwamoto, M (1999) Matrix GLA protein is a developmental regulator of chondrocyte mineralization and, when constitutively expressed, blocks endochondral and intramembranous ossification in the limb. Journal of Cell Biology 147, 10971098.CrossRefGoogle ScholarPubMed
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