Nutrition Research
Volume 29, Issue 4 , Pages 221-228 , April 2009

High-dose vitamin K supplementation reduces fracture incidence in postmenopausal women: a review of the literature

  • Jun Iwamoto

      Affiliations

    • Institute for Integrated Sports Medicine, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan
    • Corresponding Author InformationCorresponding author. Tel.: +81 3 3353 1211x63180; fax: +81 3 3352 9467.
  • ,
  • Yoshihiro Sato

      Affiliations

    • Department of Neurology, Mitate Hospital, Tagawa, Fukuoka 826-0041, Japan
  • ,
  • Tsuyoshi Takeda

      Affiliations

    • Institute for Integrated Sports Medicine, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan
  • ,
  • Hideo Matsumoto

      Affiliations

    • Institute for Integrated Sports Medicine, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan

Received 4 February 2009 ,Revised 30 March 2009 ,Accepted 31 March 2009.

References 

  1. Berkner KL. Vitamin K–dependent carboxylation. Vitam Horm. 2008;78:131–156
  2. Berkner KL. The vitamin K–dependent carboxylase. Annu Rev Nutr. 2005;25:127–149
  3. Berkner KL, Runge KW. The physiology of vitamin K nutriture and vitamin K–dependent protein function in atherosclerosis. J Thromb Haemost. 2004;2:2118–2132
  4. Cranenburg EC, Vermeer C, Koos R, Boumans ML, Hackeng TM, Bouwman FG, et al. The circulating inactive form of matrix Gla protein (ucMGP) as a biomarker for cardiovascular calcification. J Vasc Res. 2008;45:427–436
  5. Schurgers LJ, Spronk HM, Skepper JN, Hackeng TM, Shanahan CM, Vermeer C, et al. Post-translational modifications regulate matrix Gla protein function: importance for inhibition of vascular smooth muscle cell calcification. J Thromb Haemost. 2007;5:2503–2511
  6. Wallin R, Schurgers L, Wajih N. Effects of the blood coagulation vitamin K as an inhibitor of arterial calcification. Thromb Res. 2008;122:411–417
  7. Hauschka PV, Lian JB, Cole DEC, Gundberg CM. Osteocalcin and matrix Gla protein: vitamin K–dependent proteins in bone. Physiol Rev. 1989;69:990–1047
  8. Koshihara Y, Hoshi K. Vitamin K2 enhances osteocalcin accumulation in the extracellular matrix of human osteoblasts in vitro. J Bone Miner Res. 1997;12:431–438
  9. Shearer MJ. Vitamin K. Lancet. 1995;345:229–234
  10. Vermeer C, Jie KSG, Knapen MHJ. Role of vitamin K in bone metabolism. Annu Rev Nutr. 1995;15:1–22
  11. Tabb MM, Sun A, Zhou C, Grün F, Errandi J, Romero K, et al. Vitamin K2 regulation of bone homeostasis is mediated by the steroid and xenobiotic receptor SXR. J Biol Chem. 2003;278:43919–43927
  12. The WHO Scientific Group. Prevention and management of osteoporosis. World Health Organ Tech Rep Ser. 2003;921:86–109
  13. Cockayne S, Adamson J, Lanham-New S, Shearer MJ, Gilbody S, Torgerson DJ. Vitamin K and the prevention of fractures: systematic review and meta-analysis of randomized controlled trials. Arch Intern Med. 2006;166:1256–1261
  14. Okano T, Shimomura Y, Yamane M, Suhara Y, Kamao M, Sugiura M, et al. Conversion of phylloquinone (Vitamin K1) into menaquinone-4 (Vitamin K2) in mice: two possible routes for menaquinone-4 accumulation in cerebra of mice. J Biol Chem. 2008;283:11270–11279
  15. Schurgers LJ, Teunissen KJ, Hamulyák K, Knapen MH, Vik H, Vermeer C. Vitamin K–containing dietary supplements: comparison of synthetic vitamin K1 and natto-derived menaquinone-7. Blood. 2007;109:3279–3283
  16. Bolton-Smith C, McMurdo ME, Paterson CR, Mole PA, Harvey JM, Fenton ST, 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. 2007;22:509–519
  17. Cheung AM, Tile L, Lee Y, Tomlinson G, Hawker G, Scher J, et al. Vitamin K supplementation in postmenopausal women with osteopenia (ECKO trial): a randomized controlled trial. PLos Med. 2008;5:e196
  18. Knapen MH, Schurgers LJ, Vermeer C. Vitamin K2 supplementation improves hip bone geometry and bone strength indices in postmenopausal women. Osteoporos Int. 2007;18:963–972
  19. Booth SL, Dallal G, Shea MK, Gundberg C, Peterson JW, Dawson-Hughes B. Effect of vitamin K supplementation on bone loss in elderly men and women. J Clin Endocrinol Metab. 2008;93:1217–1223
  20. Braam LA, Knapen MH, Geusens P, Brouns F, Hamulyák K, Gerichhausen MJ, et al. Vitamin K1 supplementation retards bone loss in postmenopausal women between 50 and 60 years of age. Calcif Tissue Int. 2003;73:21–26
  21. Shiraki M, Shiraki Y, Aoki C, Miura M. Vitamin K2 (menatetrenone) effectively prevents fractures and sustains lumbar bone mineral density in osteoporosis. J Bone Miner Res. 2000;15:515–521
  22. Inoue T, Fujita T, Kishimoto H, Makino T, Nakamura T, Nakamura T, et al. Randomized controlled study on the prevention of osteoporotic fractures (OF Study): a phase IV clinical study of 15-mg menatetrenone capsules. J Bone Miner Metab. 2009;27:66–75
  23. Orimo H, Fujita T, Onomura T, Inoue T, Kushida K, Shiraki M. Clinical evaluation of soft capsule menatetrenone (Ea-0167) in the treatment of osteoporosis. Late Phase II Dose Study. J New Remedies Clinics. 1992;41:1249–1279[in Japanese]
  24. Centre for Evidence-Based Medicene . Oxford-centre evidence based medicine. Levels of evidence and grades of recommendation. http://www.cebm.net/levels_of_evidence.asp
  25. Ducy P, Desbois C, Boyce B, Pinero G, Story B, Dunstan C, et al. Increased bone formation in osteocalcin-deficient mice. Nature. 1996;382:448–452
  26. Chattopadhyay N, Brown EM. Cellular “sensing" of extracellular calcium (Ca(2+)(0)): emerging roles in regulating diverse physiological functions. Cell Signal. 2000;12:361–366
  27. Pi M, Faber P, Ekema G, Jackson PD, Ting A, Wang N, et al. Identification of a novel extracellular cation-sensing G-protein–coupled receptor. J Biol Chem. 2005;280:40201–40209
  28. Booth SL, Tucker KL, Chen H, Hannan MT, Gagnon DR, Cupples LA, et al. Dietary vitamin K intakes are associated with hip fracture but not with bone mineral density in elderly men and women. Am J Clin Nutr. 2000;71:1201–1208
  29. Kaneki M, Hodges SJ, Hosoi T, Fujiwara S, Lyons A, Crean SJ, et al. Japanese fermented soybean food as the major determinant of the large geographic difference in circulating levels of vitamin K2: possible implications for hip-fracture risk. Nutrition. 2001;17:315–321
  30. Szulc P, Chapuy MC, Meunier PJ, Delmas PD. Serum undercarboxylated osteocalcin is a marker of the risk of hip fracture in elderly women. J Clin Invest. 1993;91:1769–1774
  31. Szulc P, Chapuy MC, Meunier PJ, Delmas PD. Serum undercarboxylated osteocalcin is a marker of the risk of hip fracture: a three year follow-up study. Bone. 1996;18:487–488
  32. Vergnaud P, Garnero P, Meunier PJ, Breart G, Kamihagi K, Delmas PD. Undercarboxylated osteocalcin measured with a specific immunoassay predicts hip fracture in elderly women: the EPIDOS Study. J Clin Endocrinol Metab. 1997;82:719–724
  33. Luukinen H, Käkönen SM, Pettersson K, Koski K, Laippala P, Lövgren T, et al. Strong prediction of fractures among older adults by the ratio of carboxylated to total serum osteocalcin. J Bone Miner Res. 2000;15:2473–2478
  34. Feskanich D, Weber P, Willett WC, Rockett H, Booth SL, Colditz GA. Vitamin K intake and hip fractures in women: a prospective study. Am J Clin Nutr. 1999;69:74–79
  35. Tsugawa N, Shiraki M, Suhara Y, Kamao M, Ozaki R, Tanaka K, et al. Low plasma phylloquinone concentration is associated with high incidence of vertebral fracture in Japanese women. J Bone Miner Metab. 2008;26:79–85
  36. NIH Consensus Development Panel on Osteoporosis Prevention, Diagnosis, and Therapy . Osteoporosis prevention, diagnosis, and therapy. JAMA. 2001;285:785–795
  37. Kanis JA, Johnell O, Oden A, Jonsson B, Dawsopn A, Dere W. Risk of hip fracture derived from relative risks: an analysis applied to the population of Sweden. Osteoporos Int. 2000;11:120–127
  38. Kinoshita H, Nakagawa K, Narusawa K, Goseki-Sone M, Fukushi-Irie M, Mizoi L, et al. A functional single nucleotide polymorphism in the vitamin-K–dependent gamma-glutamyl carboxylase gene (Arg325Gln) is associated with bone mineral density in elderly Japanese women. Bone. 2007;40:451–456
  39. Hara K, Akiyama Y, Nakamura T, Murota S, Morita I. The inhibitory effect of vitamin K2 (menatetrenone) on bone resorption may be related to its side chain. Bone. 1995;16:179–184
  40. Hara K, Akiyama Y, Tajima T, Shiraki M. Menatetrenone inhibits bone resorption partly through inhibition of PGE2 synthesis in vitro. J Bone Miner Res. 1993;8:535–542
  41. Binkley N, Harke J, Krueger D, Engelke J, Vallarta-Ast N, Gemar D, 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. 2008;[Online publication]
  42. Sato Y, Inose M, Higuchi I, Higuchi F, Kondo I. Changes in the supporting muscles of the fractured hip in elderly women. Bone. 2002;30:325–330
  43. Bischoff-Ferrari HA, Dawson-Hughes B, Willett WC, Staehelin HB, Bazemore MG, Zee RY, et al. Effect of vitamin D on falls: a meta-analysis. JAMA. 2004;291:1999–2006
  44. Bischoff-Ferrari HA, Willett WC, Wong JB, Giovannucci E, Dietrich T, Dawson-Hughes B. Fracture prevention with vitamin D supplementation: a meta-analysis of randomized controlled trials. JAMA. 2005;293:2257–2264
  45. Nakamura K. Vitamin D insufficiency in Japanese populations: from the viewpoint of the prevention of osteoporosis. J Bone Miner Metab. 2006;24:1–6
  46. Jesudason D, Need AG, Horowitz M, O'Loughlin PD, Morris HA, Nordin BE. Relationship between serum 25-hydroxyvitamin D and bone resorption markers in vitamin D insufficiency. Bone. 2002;31:626–630

PII: S0271-5317(09)00057-8

doi: 10.1016/j.nutres.2009.03.012

Nutrition Research
Volume 29, Issue 4 , Pages 221-228 , April 2009