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Published in: Osteoporosis International 8/2006

01-08-2006 | Original Article

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

Authors: L. Rejnmark, P. Vestergaard, P. Charles, A. P. Hermann, C. Brot, P. Eiken, L. Mosekilde

Published in: Osteoporosis International | Issue 8/2006

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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.
Literature
1.
go back to reference Booth SL, Suttie J (1998) Dietary intake and adequacy of vitamin K1. J Nutr 128:785–788PubMed Booth SL, Suttie J (1998) Dietary intake and adequacy of vitamin K1. J Nutr 128:785–788PubMed
2.
go back to reference 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 8:535–542PubMed 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 8:535–542PubMed
3.
go back to reference 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 27:769–776PubMedCrossRef 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 27:769–776PubMedCrossRef
4.
go back to reference Berkner KL (2000) The vitamin K-dependent carboxylase. J Nutr 130:1877–1880PubMed Berkner KL (2000) The vitamin K-dependent carboxylase. J Nutr 130:1877–1880PubMed
5.
go back to reference Kalkwarf HJ, Khoury JC, Bean J, Elliot JG (2004) Vitamin K, bone turnover, and bone mass in girls. Am J Clin Nutr 80:1075–1080PubMed Kalkwarf HJ, Khoury JC, Bean J, Elliot JG (2004) Vitamin K, bone turnover, and bone mass in girls. Am J Clin Nutr 80:1075–1080PubMed
6.
go back to reference 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 9:1591–1595PubMed 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 9:1591–1595PubMed
7.
go back to reference 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 89:4904–4909PubMedCrossRef 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 89:4904–4909PubMedCrossRef
8.
go back to reference 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 18:487–488PubMedCrossRef 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 18:487–488PubMedCrossRef
9.
go back to reference 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 82:719–724PubMedCrossRef 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 82:719–724PubMedCrossRef
10.
go back to reference 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 91:1769–1774PubMedCrossRef 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 91:1769–1774PubMedCrossRef
11.
go back to reference 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 8:1241–1245PubMedCrossRef 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 8:1241–1245PubMedCrossRef
12.
go back to reference 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 60:1268–1269PubMedCrossRef 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 60:1268–1269PubMedCrossRef
13.
go back to reference 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 15:2473–2478PubMedCrossRef 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 15:2473–2478PubMedCrossRef
14.
go back to reference Resch H, Pietschmann P, Krexner E, Willvonseder R (1991) Decreased peripheral bone mineral content in patients under anticoagulant therapy with phenprocoumon. Eur Heart J 12:439–441PubMed Resch H, Pietschmann P, Krexner E, Willvonseder R (1991) Decreased peripheral bone mineral content in patients under anticoagulant therapy with phenprocoumon. Eur Heart J 12:439–441PubMed
15.
go back to reference Fiore CE, Tamburino C, Foti R, Grimaldi D (1990) Reduced axial bone mineral content in patients taking an oral anticoagulant. South Med J 83:538–542PubMed Fiore CE, Tamburino C, Foti R, Grimaldi D (1990) Reduced axial bone mineral content in patients taking an oral anticoagulant. South Med J 83:538–542PubMed
16.
go back to reference 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 9:441–448PubMedCrossRef 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 9:441–448PubMedCrossRef
17.
go back to reference 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 159:1750–1756PubMedCrossRef 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 159:1750–1756PubMedCrossRef
18.
go back to reference 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 128:829–832PubMed 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 128:829–832PubMed
19.
go back to reference 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 94:62–68PubMedCrossRef 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 94:62–68PubMedCrossRef
20.
go back to reference 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 77:512–516PubMed 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 77:512–516PubMed
21.
go back to reference 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 71:1201–1208PubMed 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 71:1201–1208PubMed
22.
go back to reference 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 69:74–79PubMed 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 69:74–79PubMed
23.
go back to reference Jadad AR (1998) Randomised controlled trials. A user’s guide, 1st edn. BMJ Books, London Jadad AR (1998) Randomised controlled trials. A user’s guide, 1st edn. BMJ Books, London
24.
go back to reference 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 31:207–219PubMedCrossRef 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 31:207–219PubMedCrossRef
25.
go back to reference 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 28:137–145PubMedCrossRef 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 28:137–145PubMedCrossRef
26.
go back to reference Moller A (1989) Food composition tables. Publication No. SC3. The Danish National Food Agency, Copenhagen Moller A (1989) Food composition tables. Publication No. SC3. The Danish National Food Agency, Copenhagen
27.
go back to reference 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 16:385–390PubMedCrossRef 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 16:385–390PubMedCrossRef
28.
go back to reference 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, DC 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, DC
29.
go back to reference 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, Italy 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, Italy
30.
go back to reference 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 87:605–613PubMedCrossRef 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 87:605–613PubMedCrossRef
31.
go back to reference Price R, Shearer MJ, Bolton-Smith C (1996) Daily and seasonal variation in phylloquinone (vitamin K1) intake in Scotland. Proc Nutr Soc 55:244A Price R, Shearer MJ, Bolton-Smith C (1996) Daily and seasonal variation in phylloquinone (vitamin K1) intake in Scotland. Proc Nutr Soc 55:244A
32.
go back to reference 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 49:832–841PubMed 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 49:832–841PubMed
33.
go back to reference 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 160:59–67PubMedCrossRef 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 160:59–67PubMedCrossRef
34.
go back to reference 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 4:255–264PubMedCrossRef 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 4:255–264PubMedCrossRef
35.
go back to reference 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 100:1201–1204PubMedCrossRef 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 100:1201–1204PubMedCrossRef
36.
go back to reference 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 73:21–26PubMedCrossRef 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 73:21–26PubMedCrossRef
37.
go back to reference 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 111:1001–1005PubMed 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 111:1001–1005PubMed
Metadata
Title
No effect of vitamin K1 intake on bone mineral density and fracture risk in perimenopausal women
Authors
L. Rejnmark
P. Vestergaard
P. Charles
A. P. Hermann
C. Brot
P. Eiken
L. Mosekilde
Publication date
01-08-2006
Publisher
Springer-Verlag
Published in
Osteoporosis International / Issue 8/2006
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI
https://doi.org/10.1007/s00198-005-0044-3

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