Advertisement

Osteoporosis International

, Volume 17, Issue 8, pp 1122–1132 | Cite as

No effect of vitamin K1 intake on bone mineral density and fracture risk in perimenopausal women

  • L. Rejnmark
  • P. Vestergaard
  • P. Charles
  • A. P. Hermann
  • C. Brot
  • P. Eiken
  • L. Mosekilde
Original Article

Abstract

Introduction

Vitamin K functions as a co-factor in the post-translational carboxylation of several bone proteins, including osteocalcin.

Aim

The aim of this study was to investigate the relationship between vitamin K1 intake and bone mineral density (BMD) and fracture risk in a perimenopausal Danish population.

Design

The study was performed within the Danish Osteoporosis Prevention Study (DOPS), including a population-based cohort of 2,016 perimenopausal women. During the study approximately 50% of the women received hormone replacement therapy (HRT). Associations between vitamin K1 intake and BMD were assessed at baseline and after 5-years of follow-up (cross-sectional design). Moreover, associations between vitamin K1 intake and 5-year and 10-year changes in BMD were studied (follow-up design). Finally, fracture risk was assessed in relation to vitamin K1 intake (nested case–control design).

Results

In our cohort, dietary vitamin K1 intake (60 μg/day) was close to the daily intake recommended by the Food and Agriculture Organization (FAO). Cross-sectional and longitudinal analyses showed no associations between intake of vitamin K1 and BMD of the femoral neck or lumbar spine. Neither did BMD differ between those 5% that had the highest vitamin K1 intake and those 5% that had the lowest. During the 10-years of follow-up, 360 subjects sustained a fracture (cases). In a comparison between the cases and 1,440 controls, logistic regression analyses revealed no difference in vitamin K1 intake between cases and controls.

Conclusion

In a group of perimenopausal and early postmenopausal women, vitamin K1 intake was not associated with effects on BMD or fracture risk.

Keywords

Bone mineral density Fracture Osteoporosis Phylloquinone Vitamin K Women 

Notes

Acknowledgments

The project was made possible by a grant from Karen Elise Jensen’s Foundation, Denmark. Drugs were provided free of charge by Novo Nordic, Denmark, Leo Pharmaceutical products A/S, Denmark, and Ciba Geigy, Denmark.

References

  1. 1.
    Booth SL, Suttie J (1998) Dietary intake and adequacy of vitamin K1. J Nutr 128:785–788PubMedGoogle Scholar
  2. 2.
    Hara K, Akiyama Y, Tajima T, Shiraki M (1993) Menatetrenone inhibits bone resorption partly through inhibition of PGE2 synthesis in vitro. J Bone Miner Res 8:535–542PubMedGoogle Scholar
  3. 3.
    Takeuchi Y, Suzawa M, Fukumoto S, Fujita T (2000) Vitamin K(2) inhibits adipogenesis, osteoclastogenesis, and ODF/RANK ligand expression in murine bone marrow cell cultures. Bone 27:769–776PubMedCrossRefGoogle Scholar
  4. 4.
    Berkner KL (2000) The vitamin K-dependent carboxylase. J Nutr 130:1877–1880PubMedGoogle Scholar
  5. 5.
    Kalkwarf HJ, Khoury JC, Bean J, Elliot JG (2004) Vitamin K, bone turnover, and bone mass in girls. Am J Clin Nutr 80:1075–1080PubMedGoogle Scholar
  6. 6.
    Szulc P, Arlot M, Chapuy MC, Duboeuf F, Meunier PJ, Delmas PD (1994) Serum undercarboxylated osteocalcin correlates with hip bone mineral density in elderly women. J Bone Miner Res 9:1591–1595PubMedGoogle Scholar
  7. 7.
    Booth SL, Broe KE, Peterson JW, Cheng DM, Dawson-Hughes B, Gundberg CM, Cupples LA, Wilson PWF, Kiel DP (2004) Associations between vitamin K biochemical measures and bone mineral density in men and women. J Clin Endocrinol Metab 89:4904–4909PubMedCrossRefGoogle Scholar
  8. 8.
    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 18:487–488PubMedCrossRefGoogle Scholar
  9. 9.
    Vergnaud P, Garnero P, Meunier PJ, Breart G, Kamihagi K, Delmas PD (1997) Undercarboxylated osteocalcin measured with a specific immunoassay predicts hip fracture in elderly women: the EPIDOS study. J Clin Endocrinol Metab 82:719–724PubMedCrossRefGoogle Scholar
  10. 10.
    Szulc P, Chapuy MC, Meunier PJ, Delmas PD (1993) Serum undercarboxylated osteocalcin is a marker of the risk of hip fracture in elderly women. J Clin Invest 91:1769–1774PubMedCrossRefGoogle Scholar
  11. 11.
    Hodges SJ, Akesson K, Vergnaud P, Obrant K, Delmas PD (1993) Circulating levels of vitamins K1 and K2 decreased in elderly women with hip fracture. J Bone Miner Res 8:1241–1245PubMedCrossRefGoogle Scholar
  12. 12.
    Hart JP, Shearer MJ, Klenerman L, Catterall A, Reeve J, Sambrook PN, Dodds RA, Bitensky L, Chayen J (1985) Electrochemical detection of depressed circulating levels of vitamin K1 in osteoporosis. J Clin Endocrinol Metab 60:1268–1269PubMedCrossRefGoogle Scholar
  13. 13.
    Luukinen H, Kakonen SM, Pettersson K, Koski K, Laippala P, Lovgren T, Kivela SL, Vaananen HK (2000) Strong prediction of fractures among older adults by the ratio of carboxylated to total serum osteocalcin. J Bone Miner Res 15:2473–2478PubMedCrossRefGoogle Scholar
  14. 14.
    Resch H, Pietschmann P, Krexner E, Willvonseder R (1991) Decreased peripheral bone mineral content in patients under anticoagulant therapy with phenprocoumon. Eur Heart J 12:439–441PubMedGoogle Scholar
  15. 15.
    Fiore CE, Tamburino C, Foti R, Grimaldi D (1990) Reduced axial bone mineral content in patients taking an oral anticoagulant. South Med J 83:538–542PubMedGoogle Scholar
  16. 16.
    Caraballo PJ, Gabriel SE, Castro MR, Atkinson EJ, Melton LJ III (1999) Changes in bone density after exposure to oral anticoagulants: a meta-analysis. Osteoporos Int 9:441–448PubMedCrossRefGoogle Scholar
  17. 17.
    Caraballo PJ, Heit JA, Atkinson EJ, Silverstein MD, O’Fallon WM, Castro MR, Melton III LJ (1999) Long-term use of oral anticoagulants and the risk of fracture. Arch Intern Med 159:1750–1756PubMedCrossRefGoogle Scholar
  18. 18.
    Jamal SA, Browner WS, Bauer DC, Cummings SR (1998) Warfarin use and risk for osteoporosis in elderly women. Study of Osteoporotic Fractures Research Group. Ann Intern Med 128:829–832PubMedGoogle Scholar
  19. 19.
    Rosen HN, Maitland LA, Suttie JW, Manning WJ, Glynn RJ, Greenspan SL (1993) Vitamin K and maintenance of skeletal integrity in adults. Am J Med 94:62–68PubMedCrossRefGoogle Scholar
  20. 20.
    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. Am J Clin Nutr 77:512–516PubMedGoogle Scholar
  21. 21.
    Booth SL, Tucker KL, Chen H, Hannan MT, Gagnon DR, Cupples LA, Wilson PWF, 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. Am J Clin Nutr 71:1201–1208PubMedGoogle Scholar
  22. 22.
    Feskanich D, Weber P, Willett WC, Rockett H, Booth SL, Colditz GA (1999) Vitamin K intake and hip fractures in women: a prospective study. Am J Clin Nutr 69:74–79PubMedGoogle Scholar
  23. 23.
    Jadad AR (1998) Randomised controlled trials. A user’s guide, 1st edn. BMJ Books, LondonGoogle Scholar
  24. 24.
    Mosekilde L, Hermann AP, Beck NH, Charles P, Nielsen SP, Sorensen OH (1999) The Danish Osteoporosis Prevention Study (DOPS): project design and inclusion of 2000 normal perimenopausal women. Maturitas 31:207–219PubMedCrossRefGoogle Scholar
  25. 25.
    Vestergaard P, Hermann AP, Gram J, Jensen LB, Kolthoff N, Abrahamsen B, Brot C, Eiken P (1997) Improving compliance with hormonal replacement therapy in primary osteoporosis prevention. Maturitas 28:137–145PubMedCrossRefGoogle Scholar
  26. 26.
    Moller A (1989) Food composition tables. Publication No. SC3. The Danish National Food Agency, CopenhagenGoogle Scholar
  27. 27.
    Abrahamsen B, Gram J, Hansen TB, Beck-Nielsen H (1995) Cross calibration of QDR-2000 and QDR-1000 dual-energy X-ray densitometers for bone mineral and soft-tissue measurements. Bone 16:385–390PubMedCrossRefGoogle Scholar
  28. 28.
    The Food and Nutrition Board (2000) 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, DCGoogle Scholar
  29. 29.
    Anon (2002) Human vitamin and mineral requirements: report of a joint FAO/WHO expert consultation, Bangkok, Thailand. World Health Organization, Food and Agriculture Organization of the United Nations, Rome, ItalyGoogle Scholar
  30. 30.
    Thane CW, Paul AA, Bates CJ, Bolton-Smith C, Prentice A, Shearer MJ (2002) Intake and sources of phylloquinone (vitamin K1): variation with socio-demographic and lifestyle factors in a national sample of British elderly people. Br J Nutr 87:605–613PubMedCrossRefGoogle Scholar
  31. 31.
    Price R, Shearer MJ, Bolton-Smith C (1996) Daily and seasonal variation in phylloquinone (vitamin K1) intake in Scotland. Proc Nutr Soc 55:244AGoogle Scholar
  32. 32.
    Booth SL, Sokoll LJ, O’Brien ME, Tucker K, Dawson-Hughes B, Sadowski JA (1995) Assessment of dietary phylloquinone intake and vitamin K status in postmenopausal women. Eur J Clin Nutr 49:832–841PubMedGoogle Scholar
  33. 33.
    Michels KB, Bingham SA, Luben R, Welch AA, Day NE (2004) The effect of correlated measurement error in multivariate models of diet. Am J Epidemiol 160:59–67PubMedCrossRefGoogle Scholar
  34. 34.
    Ambrosini GL, de Klerk NH, Musk AW, Mackerras D (2001) Agreement between a brief food frequency questionnaire and diet records using two statistical methods. Public Health Nutr 4:255–264PubMedCrossRefGoogle Scholar
  35. 35.
    McKeown NM, Rasmussen HM, Charnley JM, Wood RJ, Booth SL (2000) Accuracy of phylloquinone (vitamin K-1) data in 2 nutrient databases as determined by direct laboratory analysis of diets. J Am Diet Assoc 100:1201–1204PubMedCrossRefGoogle Scholar
  36. 36.
    Braam LA, Knapen MH, Geusens P, Brouns F, Hamulyak K, Gerichhausen MJ, Vermeer C (2003) Vitamin K1 supplementation retards bone loss in postmenopausal women between 50 and 60 years of age. Calcif Tissue Int 73:21–26PubMedCrossRefGoogle Scholar
  37. 37.
    Knapen MH, Hamulyak K, Vermeer C (1989) The effect of vitamin K supplementation on circulating osteocalcin (bone Gla protein) and urinary calcium excretion. Ann Intern Med 111:1001–1005PubMedGoogle Scholar

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2006

Authors and Affiliations

  • L. Rejnmark
    • 1
  • P. Vestergaard
    • 1
  • P. Charles
    • 1
  • A. P. Hermann
    • 2
  • C. Brot
    • 3
  • P. Eiken
    • 4
  • L. Mosekilde
    • 1
  1. 1.Department of Endocrinology and Metabolism C, Aarhus SygehusAarhus University HospitalAarhus CDenmark
  2. 2.Department of EndocrinologyOdense University HospitalOdenseDenmark
  3. 3.The Osteoporosis Research CentreHvidovre HospitalHvidovreDenmark
  4. 4.Department of Endocrinology and Clinical Physiology and Nuclear MedicineHilleroed HospitalHilleroedDenmark

Personalised recommendations