Skip to main content
Erschienen in: Osteoporosis International 9/2013

01.09.2013 | Original Article

Three-year low-dose menaquinone-7 supplementation helps decrease bone loss in healthy postmenopausal women

verfasst von: M. H. J. Knapen, N. E. Drummen, E. Smit, C. Vermeer, E. Theuwissen

Erschienen in: Osteoporosis International | Ausgabe 9/2013

Einloggen, um Zugang zu erhalten

Abstract

Summary

We have investigated whether low-dose vitamin K2 supplements (menaquinone-7, MK-7) could beneficially affect bone health. Next to an improved vitamin K status, MK-7 supplementation significantly decreased the age-related decline in bone mineral density and bone strength. Low-dose MK-7 supplements may therefore help postmenopausal women prevent bone loss.

Introduction

Despite contradictory data on vitamin K supplementation and bone health, the European Food Safety Authorities (EFSA) accepted the health claim on vitamin K’s role in maintenance of normal bone. In line with EFSA’s opinion, we showed that 3-year high-dose vitamin K1 (phylloquinone) and K2 (short-chain menaquinone-4) supplementation improved bone health after menopause. Because of the longer half-life and greater potency of the long-chain MK-7, we have extended these investigations by measuring the effect of low-dose MK-7 supplementation on bone health.

Methods

Healthy postmenopausal women (n = 244) received for 3 years placebo or MK-7 (180 μg MK-7/day) capsules. Bone mineral density of lumbar spine, total hip, and femoral neck was measured by DXA; bone strength indices of the femoral neck were calculated. Vertebral fracture assessment was performed by DXA and used as measure for vertebral fractures. Circulating uncarboxylated osteocalcin (ucOC) and carboxylated OC (cOC) were measured; the ucOC/cOC ratio served as marker of vitamin K status. Measurements occurred at baseline and after 1, 2, and 3 years of treatment.

Results

MK-7 intake significantly improved vitamin K status and decreased the age-related decline in BMC and BMD at the lumbar spine and femoral neck, but not at the total hip. Bone strength was also favorably affected by MK-7. MK-7 significantly decreased the loss in vertebral height of the lower thoracic region at the mid-site of the vertebrae.

Conclusions

MK-7 supplements may help postmenopausal women to prevent bone loss. Whether these results can be extrapolated to other populations, e.g., children and men, needs further investigation.
Literatur
1.
Zurück zum Zitat McCann JC, Ames BN (2009) Vitamin K, an example of triage theory: is micronutrient inadequacy linked to diseases of aging? Am J Clin Nutr 90:889–907PubMedCrossRef McCann JC, Ames BN (2009) Vitamin K, an example of triage theory: is micronutrient inadequacy linked to diseases of aging? Am J Clin Nutr 90:889–907PubMedCrossRef
2.
Zurück zum Zitat Shearer MJ, Newman P (2008) Metabolism and cell biology of vitamin K. Thromb Haemost 100:530–47PubMed Shearer MJ, Newman P (2008) Metabolism and cell biology of vitamin K. Thromb Haemost 100:530–47PubMed
3.
Zurück zum Zitat Theuwissen E, Smit E, Vermeer C (2012) The role of vitamin K in soft-tissue calcification. Adv Nutr 3:166–73PubMedCrossRef Theuwissen E, Smit E, Vermeer C (2012) The role of vitamin K in soft-tissue calcification. Adv Nutr 3:166–73PubMedCrossRef
4.
Zurück zum Zitat Price PA, Toroian D, Lim JE (2009) Mineralization by inhibitor exclusion: the calcification of collagen with fetuin. J Biol Chem 284:17092–101PubMedCrossRef Price PA, Toroian D, Lim JE (2009) Mineralization by inhibitor exclusion: the calcification of collagen with fetuin. J Biol Chem 284:17092–101PubMedCrossRef
5.
Zurück zum Zitat 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 18:487–8PubMedCrossRef 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 18:487–8PubMedCrossRef
6.
Zurück zum Zitat 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. Am J Clin Nutr 71:1201–8PubMed 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. Am J Clin Nutr 71:1201–8PubMed
7.
Zurück zum Zitat 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 15:2473–8PubMedCrossRef 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 15:2473–8PubMedCrossRef
8.
Zurück zum Zitat Knapen MH, Nieuwenhuijzen Kruseman AC, Wouters RS, Vermeer C (1998) Correlation of serum osteocalcin fractions with bone mineral density in women during the first 10 years after menopause. Calcif Tissue Int 63:375–9PubMedCrossRef Knapen MH, Nieuwenhuijzen Kruseman AC, Wouters RS, Vermeer C (1998) Correlation of serum osteocalcin fractions with bone mineral density in women during the first 10 years after menopause. Calcif Tissue Int 63:375–9PubMedCrossRef
9.
Zurück zum Zitat Apalset EM, Gjesdal CG, Eide GE, Tell GS (2011) Intake of vitamin K1 and K2 and risk of hip fractures: The Hordaland Health Study. Bone 49:990–5PubMedCrossRef Apalset EM, Gjesdal CG, Eide GE, Tell GS (2011) Intake of vitamin K1 and K2 and risk of hip fractures: The Hordaland Health Study. Bone 49:990–5PubMedCrossRef
10.
Zurück zum Zitat Cheung AM, Tile L, Lee Y, Tomlinson G, Hawker G, Scher J, Hu H, Vieth R, Thompson L, Jamal S, Josse R (2008) Vitamin K supplementation in postmenopausal women with osteopenia (ECKO trial): a randomized controlled trial. PLoS medicine 5:e196PubMedCrossRef Cheung AM, Tile L, Lee Y, Tomlinson G, Hawker G, Scher J, Hu H, Vieth R, Thompson L, Jamal S, Josse R (2008) Vitamin K supplementation in postmenopausal women with osteopenia (ECKO trial): a randomized controlled trial. PLoS medicine 5:e196PubMedCrossRef
11.
Zurück zum Zitat Bolton-Smith C, McMurdo ME, Paterson CR, Mole PA, Harvey JM, Fenton ST, Prynne CJ, Mishra GD, Shearer MJ (2007) 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 22:509–19PubMedCrossRef Bolton-Smith C, McMurdo ME, Paterson CR, Mole PA, Harvey JM, Fenton ST, Prynne CJ, Mishra GD, Shearer MJ (2007) 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 22:509–19PubMedCrossRef
12.
Zurück zum Zitat Knapen MH, Schurgers LJ, Vermeer C (2007) Vitamin K2 supplementation improves hip bone geometry and bone strength indices in postmenopausal women. Osteoporos Int 18:963–72PubMedCrossRef Knapen MH, Schurgers LJ, Vermeer C (2007) Vitamin K2 supplementation improves hip bone geometry and bone strength indices in postmenopausal women. Osteoporos Int 18:963–72PubMedCrossRef
13.
Zurück zum Zitat Booth SL, Dallal G, Shea MK, Gundberg C, Peterson JW, Dawson-Hughes B (2008) Effect of vitamin K supplementation on bone loss in elderly men and women. J Clin Endocrinol Metab 93:1217–23PubMedCrossRef Booth SL, Dallal G, Shea MK, Gundberg C, Peterson JW, Dawson-Hughes B (2008) Effect of vitamin K supplementation on bone loss in elderly men and women. J Clin Endocrinol Metab 93:1217–23PubMedCrossRef
14.
Zurück zum Zitat Theuwissen E, Cranenburg EC, Knapen MH, Magdeleyns EJ, Teunissen KJ, Schurgers LJ, Smit E, Vermeer C (2012) Low-dose menaquinone-7 supplementation improved extra-hepatic vitamin K status, but had no effect on thrombin generation in healthy subjects. Br J Nutr 108:1652–7PubMedCrossRef Theuwissen E, Cranenburg EC, Knapen MH, Magdeleyns EJ, Teunissen KJ, Schurgers LJ, Smit E, Vermeer C (2012) Low-dose menaquinone-7 supplementation improved extra-hepatic vitamin K status, but had no effect on thrombin generation in healthy subjects. Br J Nutr 108:1652–7PubMedCrossRef
15.
Zurück zum Zitat (2009) Scientific Opinion on the substantiation of health claims related to vitamin K and maintenance of bone pursuant to Article 13(1) of Regulation (EC) No 1924/20061. The EFSA Journal 7:1128. (2009) Scientific Opinion on the substantiation of health claims related to vitamin K and maintenance of bone pursuant to Article 13(1) of Regulation (EC) No 1924/20061. The EFSA Journal 7:1128.
16.
Zurück zum Zitat Cockayne S, Adamson J, Lanham-New S, Shearer MJ, Gilbody S, Torgerson DJ (2006) Vitamin K and the prevention of fractures: systematic review and meta-analysis of randomized controlled trials. Arch Intern Med 166:1256–61PubMedCrossRef Cockayne S, Adamson J, Lanham-New S, Shearer MJ, Gilbody S, Torgerson DJ (2006) Vitamin K and the prevention of fractures: systematic review and meta-analysis of randomized controlled trials. Arch Intern Med 166:1256–61PubMedCrossRef
17.
Zurück zum Zitat Fang Y, Hu C, Tao X, Wan Y, Tao F (2012) Effect of vitamin K on bone mineral density: a meta-analysis of randomized controlled trials. J Bone Miner Metab 30:60–8PubMedCrossRef Fang Y, Hu C, Tao X, Wan Y, Tao F (2012) Effect of vitamin K on bone mineral density: a meta-analysis of randomized controlled trials. J Bone Miner Metab 30:60–8PubMedCrossRef
18.
Zurück zum Zitat Shea MK, Dallal GE, Dawson-Hughes B, Ordovas JM, O'Donnell CJ, Gundberg CM, Peterson JW, Booth SL (2008) Vitamin K, circulating cytokines, and bone mineral density in older men and women. Am J Clin Nutr 88:356–63PubMed Shea MK, Dallal GE, Dawson-Hughes B, Ordovas JM, O'Donnell CJ, Gundberg CM, Peterson JW, Booth SL (2008) Vitamin K, circulating cytokines, and bone mineral density in older men and women. Am J Clin Nutr 88:356–63PubMed
19.
Zurück zum Zitat Emaus N, Gjesdal CG, Almas B, Christensen M, Grimsgaard AS, Berntsen GK, Salomonsen L, Fonnebo V (2009) Vitamin K2 supplementation does not influence bone loss in early menopausal women: a randomised double-blind placebo-controlled trial. Osteoporos Int 21:1731–40PubMedCrossRef Emaus N, Gjesdal CG, Almas B, Christensen M, Grimsgaard AS, Berntsen GK, Salomonsen L, Fonnebo V (2009) Vitamin K2 supplementation does not influence bone loss in early menopausal women: a randomised double-blind placebo-controlled trial. Osteoporos Int 21:1731–40PubMedCrossRef
20.
Zurück zum Zitat Forli L, Bollerslev J, Simonsen S, Isaksen GA, Kvamsdal KE, Godang K, Gadeholt G, Pripp AH, Bjortuft O (2010) Dietary vitamin K2 supplement improves bone status after lung and heart transplantation. Transplantation 89:458–64PubMedCrossRef Forli L, Bollerslev J, Simonsen S, Isaksen GA, Kvamsdal KE, Godang K, Gadeholt G, Pripp AH, Bjortuft O (2010) Dietary vitamin K2 supplement improves bone status after lung and heart transplantation. Transplantation 89:458–64PubMedCrossRef
21.
Zurück zum Zitat Gundberg CM, Lian JB, Booth SL (2012) Vitamin K-dependent carboxylation of osteocalcin: friend or foe? Adv Nutr 3:149–57PubMedCrossRef Gundberg CM, Lian JB, Booth SL (2012) Vitamin K-dependent carboxylation of osteocalcin: friend or foe? Adv Nutr 3:149–57PubMedCrossRef
22.
Zurück zum Zitat Yamaguchi M, Weitzmann MN (2011) Vitamin K2 stimulates osteoblastogenesis and suppresses osteoclastogenesis by suppressing NF-kappaB activation. Int J Mol Med 27:3–14PubMed Yamaguchi M, Weitzmann MN (2011) Vitamin K2 stimulates osteoblastogenesis and suppresses osteoclastogenesis by suppressing NF-kappaB activation. Int J Mol Med 27:3–14PubMed
23.
Zurück zum Zitat Schurgers LJ, Teunissen KJ, Hamulyak K, Knapen MH, Vik H, Vermeer C (2007) Vitamin K-containing dietary supplements: comparison of synthetic vitamin K1 and natto-derived menaquinone-7. Blood 109:3279–83PubMedCrossRef Schurgers LJ, Teunissen KJ, Hamulyak K, Knapen MH, Vik H, Vermeer C (2007) Vitamin K-containing dietary supplements: comparison of synthetic vitamin K1 and natto-derived menaquinone-7. Blood 109:3279–83PubMedCrossRef
24.
Zurück zum Zitat Sato T, Schurgers LJ, Uenishi K (2012) Comparison of menaquinone-4 and menaquinone-7 bioavailability in healthy women. Nutr J 11:93PubMedCrossRef Sato T, Schurgers LJ, Uenishi K (2012) Comparison of menaquinone-4 and menaquinone-7 bioavailability in healthy women. Nutr J 11:93PubMedCrossRef
25.
Zurück zum Zitat Kaneki M, Hedges SJ, Hosoi T, Fujiwara S, Lyons A, Crean SJ, Ishida N, Nakagawa M, Takechi M, Sano Y, Mizuno Y, Hoshino S, Miyao M, Inoue S, Horiki K, Shiraki M, Ouchi Y, Orimo H (2001) 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 17:315–21PubMedCrossRef Kaneki M, Hedges SJ, Hosoi T, Fujiwara S, Lyons A, Crean SJ, Ishida N, Nakagawa M, Takechi M, Sano Y, Mizuno Y, Hoshino S, Miyao M, Inoue S, Horiki K, Shiraki M, Ouchi Y, Orimo H (2001) 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 17:315–21PubMedCrossRef
26.
Zurück zum Zitat Ikeda Y, Iki M, Morita A, Kajita E, Kagamimori S, Kagawa Y, Yoneshima H (2006) Intake of fermented soybeans, natto, is associated with reduced bone loss in postmenopausal women: Japanese Population-Based Osteoporosis (JPOS) Study. J Nutr 136:1323–8PubMed Ikeda Y, Iki M, Morita A, Kajita E, Kagamimori S, Kagawa Y, Yoneshima H (2006) Intake of fermented soybeans, natto, is associated with reduced bone loss in postmenopausal women: Japanese Population-Based Osteoporosis (JPOS) Study. J Nutr 136:1323–8PubMed
27.
Zurück zum Zitat Karlamangla AS, Barrett-Connor E, Young J, Greendale GA (2004) Hip fracture risk assessment using composite indices of femoral neck strength: the Rancho Bernardo study. Osteoporos Int 15:62–70PubMedCrossRef Karlamangla AS, Barrett-Connor E, Young J, Greendale GA (2004) Hip fracture risk assessment using composite indices of femoral neck strength: the Rancho Bernardo study. Osteoporos Int 15:62–70PubMedCrossRef
28.
Zurück zum Zitat Genant HK, Wu CY, van Kuijk C, Nevitt MC (1993) Vertebral fracture assessment using a semiquantitative technique. J Bone Miner Res 8:1137–48PubMedCrossRef Genant HK, Wu CY, van Kuijk C, Nevitt MC (1993) Vertebral fracture assessment using a semiquantitative technique. J Bone Miner Res 8:1137–48PubMedCrossRef
29.
Zurück zum Zitat Kanellakis S, Moschonis G, Tenta R, Schaafsma A, van den Heuvel EG, Papaioannou N, Lyritis G, Manios Y (2012) Changes in parameters of bone metabolism in postmenopausal women following a 12-month intervention period using dairy products enriched with calcium, vitamin D, and phylloquinone (vitamin K(1)) or menaquinone-7 (vitamin K (2)): the Postmenopausal Health Study II. Calcif Tissue Int 90:251–62PubMedCrossRef Kanellakis S, Moschonis G, Tenta R, Schaafsma A, van den Heuvel EG, Papaioannou N, Lyritis G, Manios Y (2012) Changes in parameters of bone metabolism in postmenopausal women following a 12-month intervention period using dairy products enriched with calcium, vitamin D, and phylloquinone (vitamin K(1)) or menaquinone-7 (vitamin K (2)): the Postmenopausal Health Study II. Calcif Tissue Int 90:251–62PubMedCrossRef
30.
Zurück zum Zitat 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 73:21–6PubMedCrossRef 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 73:21–6PubMedCrossRef
31.
Zurück zum Zitat Bugel S, Sorensen AD, Hels O, Kristensen M, Vermeer C, Jakobsen J, Flynn A, Molgaard C, Cashman KD (2007) Effect of phylloquinone supplementation on biochemical markers of vitamin K status and bone turnover in postmenopausal women. Br J Nutr 97:373–80PubMedCrossRef Bugel S, Sorensen AD, Hels O, Kristensen M, Vermeer C, Jakobsen J, Flynn A, Molgaard C, Cashman KD (2007) Effect of phylloquinone supplementation on biochemical markers of vitamin K status and bone turnover in postmenopausal women. Br J Nutr 97:373–80PubMedCrossRef
32.
Zurück zum Zitat Binkley N, Harke J, Krueger D, Engelke J, Vallarta-Ast N, Gemar D, Checovich M, Chappell R, Suttie J (2009) 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 24:983–91PubMedCrossRef Binkley N, Harke J, Krueger D, Engelke J, Vallarta-Ast N, Gemar D, Checovich M, Chappell R, Suttie J (2009) 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 24:983–91PubMedCrossRef
33.
Zurück zum Zitat Theuwissen E, Cranenburg EC, Knapen MH, Magdeleyns EJ, Teunissen KJ, Schurgers LJ, Smit E, Vermeer C (2012) Low-dose menaquinone-7 supplementation improved extra-hepatic vitamin K status, but had no effect on thrombin generation in healthy subjects. The British journal of nutrition 1–6 Theuwissen E, Cranenburg EC, Knapen MH, Magdeleyns EJ, Teunissen KJ, Schurgers LJ, Smit E, Vermeer C (2012) Low-dose menaquinone-7 supplementation improved extra-hepatic vitamin K status, but had no effect on thrombin generation in healthy subjects. The British journal of nutrition 1–6
34.
Zurück zum Zitat Bazzocchi A, Spinnato P, Fuzzi F, Diano D, Morselli-Labate AM, Sassi C, Salizzoni E, Battista G, Guglielmi G (2012) Vertebral fracture assessment by new dual-energy X-ray absorptiometry. Bone 50:836–41PubMedCrossRef Bazzocchi A, Spinnato P, Fuzzi F, Diano D, Morselli-Labate AM, Sassi C, Salizzoni E, Battista G, Guglielmi G (2012) Vertebral fracture assessment by new dual-energy X-ray absorptiometry. Bone 50:836–41PubMedCrossRef
35.
Zurück zum Zitat Jager PL, Jonkman S, Koolhaas W, Stiekema A, Wolffenbuttel BH, Slart RH (2011) Combined vertebral fracture assessment and bone mineral density measurement: a new standard in the diagnosis of osteoporosis in academic populations. Osteoporos Int 22:1059–68PubMedCrossRef Jager PL, Jonkman S, Koolhaas W, Stiekema A, Wolffenbuttel BH, Slart RH (2011) Combined vertebral fracture assessment and bone mineral density measurement: a new standard in the diagnosis of osteoporosis in academic populations. Osteoporos Int 22:1059–68PubMedCrossRef
Metadaten
Titel
Three-year low-dose menaquinone-7 supplementation helps decrease bone loss in healthy postmenopausal women
verfasst von
M. H. J. Knapen
N. E. Drummen
E. Smit
C. Vermeer
E. Theuwissen
Publikationsdatum
01.09.2013
Verlag
Springer London
Erschienen in
Osteoporosis International / Ausgabe 9/2013
Print ISSN: 0937-941X
Elektronische ISSN: 1433-2965
DOI
https://doi.org/10.1007/s00198-013-2325-6

Weitere Artikel der Ausgabe 9/2013

Osteoporosis International 9/2013 Zur Ausgabe

Arthropedia

Grundlagenwissen der Arthroskopie und Gelenkchirurgie. Erweitert durch Fallbeispiele, Videos und Abbildungen. 
» Jetzt entdecken

Update Orthopädie und Unfallchirurgie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.