Calcified Tissue International

, Volume 73, Issue 1, pp 21–26 | Cite as

Vitamin K1 Supplementation Retards Bone Loss in Postmenopausal Women Between 50 and 60 Years of Age

  • L. A. J. L. M. Braam
  • M. H. J. Knapen
  • P. Geusens
  • F. Brouns
  • K. Hamulyák
  • M. J. W. Gerichhausen
  • C. Vermeer
Clinical Investigations


Although several observational studies have demonstrated an association between vitamin K status and bone mineral density (BMD) in postmenopausal women, no placebo-controlled intervention trials of the effect of vitamin K1 supplementation on bone loss have been reported thus far. In the trial presented here we have investigated the potential complementary effect of vitamin K1 (1 mg/day) and a mineral + vitamin D supplement (8 µg/day) on postmenopausal bone loss. The design of our study was a randomized, double-blind, placebo-controlled intervention study; 181 healthy postmenopausal women between 50 and 60 years old were recruited, 155 of whom completed the study. During the 3-year treatment period, participants received a daily supplement containing either placebo, or calcium, magnesium, zinc, and vitamin D (MD group), or the same formulation with additional vitamin K1 (MDK group). The main outcome was the change in BMD of the femoral neck and lumbar spine after 3 years, as measured by DXA. The group receiving the supplement containing additional vitamin K1 showed reduced bone loss of the femoral neck: after 3 years the difference between the MDK and the placebo group was 1.7% (95% Cl: 0.35–3.44) and that between the MDK and MD group was 1.3% (95% Cl: 0.10–3.41). No significant differences were observed among the three groups with respect to change of BMD at the site of the lumbar spine. If co-administered with minerals and vitamin D, vitamin K1 may substantially contribute to reducing postmenopausal bone loss at the site of the femoral neck.


Vitamin K Bone loss Osteoporosis Minerals Vitamin D 



The authors wish to thank Novartis Consumer Health SA (Nyon, Switzerland) for their financial support of this study, and the Department of Nuclear Medicine at the University Hospital Maastricht for performing the DXA measurements. The statistical advice of Drs. M. Olesen (Novartis) and Dr. A. Kester (Department of Biostatistics, UM) is gratefully acknowledged. We wish to thank Professor J. Rosing for critically reading this manuscript. This study was supported by Novartis Consumer Health SA (Nyon, Switzerland) and in part by grant # 28-2817 from the Praeventiefonds (Netherlands).


  1. 1.
    Chapuy, MC, Arlot, ME, Duboeuf, F, Brun, J, Crouzet, B, Arnaud, S, Delmas, PD, Meunier, PJ 1992Vitamin D3 and calcium to prevent hip fractures in elderly women.N Engl J Med32716371642PubMedGoogle Scholar
  2. 2.
    Chapuy, MC, Arlot, ME, Delmas, PD, Meunier, PJ 1994Effect of calcium and cholecalciferol treatment for three years on hip fractures in elderly women.BMJ30810811082PubMedGoogle Scholar
  3. 3.
    Dawson-Hughes, B, Harris, SS, Krall, EA, Dallal, GE 1997Effect of calcium and vitamin D supplementation on bone density in men and women 65 years of age or older.N Engl J Med337670676Google Scholar
  4. 4.
    Lips, P, Graafmans, WC, Ooms, ME, Bezemer, PD, Bouter, LM 1996Vitamin D supplementation and fracture incidence in elderly persons. A randomized, placebo-controlled clinical trial.Ann Intern Med124400406PubMedGoogle Scholar
  5. 5.
    Ferland, G, Sadowski, JA 1992Vitamin K1 (phylloquinone) content of edible oils: effects of heating and light exposure.J Agricult Food Chem4018691873Google Scholar
  6. 6.
    Booth, SL, Sadowski, JA, Weihrauch, JL, Ferland, G 1993Vitamin K1 (phylloquinone) content of foods: a provisional table.J Food Comp Anal6109120CrossRefGoogle Scholar
  7. 7.
    Shearer, MJ, Bolton-Smith, C 2000The U.K. food data-base for vitamin K and why we need it.Food Chem68213218CrossRefGoogle Scholar
  8. 8.
    Schurgers, LJ, Vermeer, C 2000Determination of phylloquinone and menaquinones in food. Effect of food matrix on circulating vitamin K concentrations.Haemostasis30298307CrossRefPubMedGoogle Scholar
  9. 9.
    Sokoll, LJ, Sadowski, JA 1996Comparison of biochemical indexes for assessing vitamin K nutritional status in a healthy adult population.Am J Clin Nutr63566573PubMedGoogle Scholar
  10. 10.
    Sokoll, LJ, Booth, SL, O’Brien, ME, Davidson, KW, Tsaioun, KI, Sadowski, JA 1997Changes in serum osteocalcin, plasma phylloquinone, and urinary gamma-carboxyglutamic acid in response to altered intakes of dietary phylloquinone in human subjects.Am J Clin Nutr65779784PubMedGoogle Scholar
  11. 11.
    Knapen, MHJ, Hamulyak, K, Vermeer, C 1989The effect of vitamin K supplementation on circulating osteocalcin (bone Gla protein) and urinary calcium excretion.Ann Intern Med11110011005PubMedGoogle Scholar
  12. 12.
    Hart, JP, Catterall, A, Dodds, RA, Klenerman, L, Shearer, MJ, Bitensky, L, Chayen, J 1984Circulating vitamin K1 levels in fractured neck of femur [letter].Lancet2283CrossRefPubMedGoogle Scholar
  13. 13.
    Hart, JP, Shearer, MJ, Klenerman, L, Catterall, A, Reeve, J, Sambrook, PN, Dodds, RA, Bitensky, L, Chayen, J 1985Electrochemical detection of depressed circulating levels of vitamin K1 in osteoporosis.J Clin Endocrinol Metab6012681269PubMedGoogle Scholar
  14. 14.
    Szulc, P, Arlot, M, Chapuy, MC, Duboeuf, F, Meunier, PJ, Delmas, PD 1994Serum undercarboxylated osteocalcin correlates with hip bone mineral density in elderly women.J Bone Miner Res915911595PubMedGoogle Scholar
  15. 15.
    Szulc, P, Chapuy, MC, Meunier, PJ, Delmas, PD 1996Serum undercarboxylated osteocalcin is a marker of the risk of hip fracture: a three year follow-up study [see comments].Bone18487488CrossRefPubMedGoogle Scholar
  16. 16.
    Luukinen, H, Kakonen, SM, Pettersson, K, Koski, K, Laippala, P, Lovgren, T, Kivela, SL, Vaananen, HK 2000Strong prediction of fractures among older adults by the ratio of carboxylated to total serum osteocalcin.J Bone Miner Res1524732478PubMedGoogle Scholar
  17. 17.
    Fiore, CE, Tamburino, C, Foti, R, Grimaldi, D 1990Reduced axial bone mineral content in patients taking an oral anticoagulant.South Med J83538542PubMedGoogle Scholar
  18. 18.
    Monreal, M, Olive, A, Lafoz, E, del Rio, L 1991Heparins, coumarin, and bone density.Lancet338706CrossRefGoogle Scholar
  19. 19.
    Resch, H, Pietschmann, P, Krexner, E, Willvonseder, R 1991Decreased peripheral bone mineral content in patients under anticoagulant therapy with phenprocoumon.Eur Heart J12439441PubMedGoogle Scholar
  20. 20.
    Piro, LD, Whyte, MP, Murphy, WA, Birge, SJ 1982Normal cortical bone mass in patients after long-term coumadin therapy.J Clin Endocrinol Metab54470473PubMedGoogle Scholar
  21. 21.
    Houvenagel, E, Leloire, O, Vanderlinden, T, Graux, P, Dutoit, A, Tison, F, Forzy, G, Racadot, A, Vincent, G 1989The level of osteocalcin and bone mass in patients receiving anti-vitamin K agents.Rev Rhum Mal Osteoartic56677679PubMedGoogle Scholar
  22. 22.
    Rosen, HN, Maitland, LA, Suttie, JW, Manning, WJ, Glynn, RJ, Greenspan, SL 1993Vitamin K and maintenance of skeletal integrity in adults.Am J Med946268PubMedGoogle Scholar
  23. 23.
    Shiraki, M, Shiraki, Y, Aoki, C, Miura, M 2000Vitamin K2 (menatetrenone) effectively prevents fractures and sustains lumbar bone mineral density in osteoporosis.J Bone Miner Res15515521PubMedGoogle Scholar
  24. 24.
    Christiansen, C, Christensen, MS, McNair, P, Hagen, C, Stocklund, KE, Transbol, I 1980Prevention of early postmenopausal bone loss: controlled 2-year study in 315 normal females.Eur J Clin Invest10273279PubMedGoogle Scholar
  25. 25.
    Aloia, JF, Vaswani, A, Yeh, JK, Ross, PL, Flaster, E, Dilmanian, FA 1994Calcium supplementation with and without hormone replacement therapy to prevent postmenopausal bone loss.Ann Intern Med12097103PubMedGoogle Scholar
  26. 26.
    Reid, IR, Ames, RW, Evans, MC, Gamble, GD, Sharpe, SJ 1995Long-term effects of calcium supplementation on bone loss and fractures in postmenopausal women: a randomized controlled trial.Am J Med98331335CrossRefPubMedGoogle Scholar
  27. 27.
    Heaney, R 1996Design considerations for osteoporosis trials.M., R. eds. Osteoporosis.Academic PressSan Diego11251142Google Scholar
  28. 28.
    Hodges, SJ, Akesson, K, Vergnaud, P, Obrant, K, Delmas, PD 1993Circulating levels of vitamins K1 and K2 decreased in elderly women with hip fracture.J Bone Miner Res812411245PubMedGoogle Scholar
  29. 29.
    Somekawa, Y, Chigughi, M, Harada, M, Ishibashi, T 1999Use of vitamin K2 (menatetrenone) and 1,25-dihydroxyvitamin D3 in the prevention of bone loss induced by leuprolide.J Clin Endocrinol Metab8427002704PubMedGoogle Scholar
  30. 30.
    Ronden, JE, Thijssen, HH, Vermeer, C 1998Tissue distribution of K-vitamers under different nutritional regimens in the rat.Biochim Biophys Acta13791622CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2003

Authors and Affiliations

  • L. A. J. L. M. Braam
    • 1
  • M. H. J. Knapen
    • 1
  • P. Geusens
    • 2
  • F. Brouns
    • 3
  • K. Hamulyák
    • 2
  • M. J. W. Gerichhausen
    • 4
  • C. Vermeer
    • 1
  1. 1.Department of BiochemistryUniversity of MaastrichtThe Netherlands
  2. 2.Department of Internal MedicineUniversity of MaastrichtThe Netherlands
  3. 3.Department of Human BiologyUniversity of MaastrichtThe Netherlands
  4. 4.Novartis Nutrition Research AGSwitzerland

Personalised recommendations