Skip to main content
Log in

Low plasma phylloquinone concentration is associated with high incidence of vertebral fracture in Japanese women

  • ORIGINAL ARTICLE
  • Published:
Journal of Bone and Mineral Metabolism Aims and scope Submit manuscript

Abstract

It has been reported that vitamin K supplementation effectively prevents fractures and sustains bone mineral density in osteoporosis. However, there are only limited reported data concerning the association between vitamin K nutritional status and bone mineral density (BMD) or fractures in Japan. The objectives were to evaluate the association between plasma phylloquinone (K1) or menaquinone (MK-4 and MK-7) concentration and BMD or fracture in Japanese women prospectively. A total of 379 healthy women aged 30–88 years (mean age, 63.0 years) were consecutively enrolled. Plasma K1, MK-4, MK-7, and serum undercarboxylated osteocalcin (ucOC) concentrations, BMD, and incidence of vertebral fractures were evaluated. In stepwise multiple linear regression analyses, L2–4 BMD and a bone turnover marker, log K1, concentrations were independently correlated with vertebral fracture incidence. When subjects were divided into low and high K1 groups by plasma K1 concentration, the incidence of vertebral fracture in the low K1 group (14.4%) was significantly higher than that in the high K1 group (4.2%), and its age-adjusted RR was 3.58 (95% CI, 3.26–3.93). L2–4 BMD was not different between the two groups. These results suggest that subjects with vitamin K1 insufficiency in bone have increased susceptibility for vertebral fracture independently from BMD.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. G Ferland (1998) ArticleTitleThe vitamin K-dependent proteins: an update Nutr Rev 56 223–230 Occurrence Handle9735675 Occurrence Handle1:CAS:528:DyaK1MXmtlWrs70%3D Occurrence Handle10.1111/j.1753-4887.1998.tb01753.x

    Article  PubMed  CAS  Google Scholar 

  2. NC Binkley JW Suttie (1995) ArticleTitleVitamin K nutrition and osteoporosis J Nutr 125 1812–1821 Occurrence Handle7616295 Occurrence Handle1:CAS:528:DyaK2MXmvVyktbk%3D

    PubMed  CAS  Google Scholar 

  3. SL Booth KL Tucker H Chen MT Hannan DR Gagnon LA Cupples PW Wilson J Ordovas EJ Schaefer B Dawson-Hughes DP Kiel (2000) ArticleTitleDietary vitamin K intakes are associated with hip fracture but not with bone mineral density in elderly men and women Am J Clin Nutr 71 1201–1208 Occurrence Handle10799384 Occurrence Handle1:CAS:528:DC%2BD3cXivFymsbs%3D

    PubMed  CAS  Google Scholar 

  4. D Feskanich P Weber WC Willett H Rockett SL Booth GA Colditz (1999) ArticleTitleVitamin K intake and hip fractures in women: a prospective study Am J Clin Nutr 69 74–79 Occurrence Handle9925126 Occurrence Handle1:CAS:528:DyaK1MXjvFSmtA%3D%3D

    PubMed  CAS  Google Scholar 

  5. SL Booth KE Broe DR Gagnon KL Tucker MT Hannan RR McLean B Dawson-Hughes PW Wilson LA Cupples DP Kiel (2003) ArticleTitleVitamin K intake and bone mineral density in women and men Am J Clin Nutr 77 512–516 Occurrence Handle12540415 Occurrence Handle1:CAS:528:DC%2BD3sXptVentQ%3D%3D

    PubMed  CAS  Google Scholar 

  6. SL Booth KE Broe JW Peterson DM Cheng B Dawson-Hughes CM Gundberg LA Cupples PW Wilson DP Kiel (2004) ArticleTitleAssociations between vitamin K biochemical measures and bone mineral density in men and women J Clin Endocrinol Metab 89 4904–4909 Occurrence Handle15472183 Occurrence Handle10.1210/jc.2003-031673 Occurrence Handle1:CAS:528:DC%2BD2cXovVenu7k%3D

    Article  PubMed  CAS  Google Scholar 

  7. JP Hart A Catterall RA Dodds L Klenerman MJ Shearer L Bitensky J Chayen (1984) ArticleTitleCirculating vitamin K1 levels in fractured neck of femur Lancet 2 283 Occurrence Handle6146829 Occurrence Handle10.1016/S0140-6736(84)90321-0 Occurrence Handle1:STN:280:DyaL2c3mvFCquw%3D%3D

    Article  PubMed  CAS  Google Scholar 

  8. JP Hart MJ Shearer L Klenerman A Catterall J Reeve PN Sambrook RA Dodds L Bitensky J Chayen (1985) ArticleTitleElectrochemical detection of depressed circulating levels of vitamin K1 in osteoporosis J Clin Endocrinol Metab 60 1268–1269 Occurrence Handle3998071 Occurrence Handle1:STN:280:DyaL2M3gvVWqtw%3D%3D Occurrence Handle10.1210/jcem-60-6-1268

    Article  PubMed  CAS  Google Scholar 

  9. L Bitensky JP Hart A Catterall SJ Hodges MJ Pilkington J Chayen (1988) ArticleTitleCirculating vitamin K levels in patients with fractures J Bone Joint Surg Br 70 663–664 Occurrence Handle3403621 Occurrence Handle1:STN:280:DyaL1c3pvV2ksA%3D%3D

    PubMed  CAS  Google Scholar 

  10. SJ Hodges K Akesson P Vergnaud K Obrant PD Delmas (1993) ArticleTitleCirculating levels of vitamins K1 and K2 decreased in elderly women with hip fracture J Bone Miner Res 8 1241–1245 Occurrence Handle8256661 Occurrence Handle1:STN:280:DyaK2c%2FnvVyhtw%3D%3D

    PubMed  CAS  Google Scholar 

  11. M Kaneki SJ Hedges T Hosoi M Shiraki Y Ouchi H Orimo (2001) ArticleTitleJapanese 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 17 315–321 Occurrence Handle11369171 Occurrence Handle10.1016/S0899-9007(00)00554-2 Occurrence Handle1:CAS:528:DC%2BD3MXjtlChtro%3D

    Article  PubMed  CAS  Google Scholar 

  12. H Katsuyama S Ideguchi M Fukunaga T Fukunaga K Saijoh S Sunami (2004) ArticleTitlePromotion of bone formation by fermented soybean (Natto) intake in premenopausal women J Nutr Sci Vitaminol 50 114–120 Occurrence Handle15242015 Occurrence Handle1:CAS:528:DC%2BD2cXjvFeru7w%3D

    PubMed  CAS  Google Scholar 

  13. K Kawana M Takahashi H Hoshino K Kushida (2001) ArticleTitleCirculating levels of vitamin K1, menaquinone-4, and menaquinone-7 in healthy elderly Japanese women and patients with vertebral fractures and patients with hip fractures Endocr Res 27 337–343 Occurrence Handle11678581 Occurrence Handle10.1081/ERC-100106011 Occurrence Handle1:CAS:528:DC%2BD3MXotVenurg%3D

    Article  PubMed  CAS  Google Scholar 

  14. A Shiraishi S Higashi T Masaki M Saito M Ito S Ikeda T Nakamura (2002) ArticleTitleA comparison of alfacalcidol and menatetrenone for the treatment of bone loss in an ovariectomized rat model of osteoporosis Calcif Tissue Int 71 69–79 Occurrence Handle12073154 Occurrence Handle10.1007/s00223-001-2090-y Occurrence Handle1:CAS:528:DC%2BD38Xms12gtbg%3D

    Article  PubMed  CAS  Google Scholar 

  15. T Mawatari H Miura H Higaki T Moro-Oka K Kurata T Murakami Y Iwamoto (2000) ArticleTitleEffect of vitamin K2 on three-dimensional trabecular microarchitecture in ovariectomized rats J Bone Miner Res 15 1810–1817 Occurrence Handle10977000 Occurrence Handle10.1359/jbmr.2000.15.9.1810 Occurrence Handle1:CAS:528:DC%2BD3cXmsF2mtLg%3D

    Article  PubMed  CAS  Google Scholar 

  16. J Iwamoto JK Yeh T Takeda (2003) ArticleTitleEffect of vitamin K2 on cortical and cancellous bones in orchidectomized and/or sciatic neurectomized rats J Bone Miner Res 18 776–783 Occurrence Handle12674339 Occurrence Handle10.1359/jbmr.2003.18.4.776 Occurrence Handle1:CAS:528:DC%2BD3sXivFKksL8%3D

    Article  PubMed  CAS  Google Scholar 

  17. Y Iwasaki H Yamato H Murayama M Sato T Takahashi I Ezawa K Kurokawa M Fukagawa (2003) ArticleTitleCombination use of vitamin K(2) further increases bone volume and ameliorates extremely low turnover bone induced by bisphosphonate therapy in tail-suspension rats J Bone Miner Metab 21 IssueID3 154–160 Occurrence Handle12720049 Occurrence Handle10.1007/s007740300024 Occurrence Handle1:CAS:528:DC%2BD3sXjt1Gju74%3D

    Article  PubMed  CAS  Google Scholar 

  18. H Otomo A Sakai S Ikeda S Tanaka M Ito RJ Phipps T Nakamura (2004) ArticleTitleRegulation of mineral-to-matrix ratio of lumbar trabecular bone in ovariectomized rats treated with risedronate in combination with or without vitamin K2 J Bone Miner Metab 22 404–414 Occurrence Handle15316861 Occurrence Handle10.1007/s00774-004-0502-6 Occurrence Handle1:CAS:528:DC%2BD2cXmslCitLc%3D

    Article  PubMed  CAS  Google Scholar 

  19. S Matsunaga H Ito T Sakou (1999) ArticleTitleThe effect of vitamin K and D supplementation on ovariectomy-induced bone loss Calcif Tissue Int 65 285–289 Occurrence Handle10485979 Occurrence Handle10.1007/s002239900700 Occurrence Handle1:CAS:528:DyaK1MXmvFWqsLg%3D

    Article  PubMed  CAS  Google Scholar 

  20. NC Binkley DC Krueger JA Engelke AL Foley JW Suttie (2000) ArticleTitleVitamin K supplementation reduces serum concentrations of under-gamma-carboxylated osteocalcin in healthy young and elderly adults Am J Clin Nutr 72 1523–1528 Occurrence Handle11101481 Occurrence Handle1:CAS:528:DC%2BD3cXosl2mt7w%3D

    PubMed  CAS  Google Scholar 

  21. MM Tabb A Sun C Zhou F Grun J Errandi K Romero H Pham S Inoue S Mallick M Lin BM Forman B Blumberg (2003) ArticleTitleVitamin K2 regulation of bone homeostasis is mediated by the steroid and xenobiotic receptor SXR J Biol Chem 278 43919–43927 Occurrence Handle12920130 Occurrence Handle10.1074/jbc.M303136200 Occurrence Handle1:CAS:528:DC%2BD3sXoslWmsLw%3D

    Article  PubMed  CAS  Google Scholar 

  22. Y Suhara M Kamao N Tsugawa T Okano (2005) ArticleTitleMethod for the determination of vitamin K homologues in human plasma using high-performance liquid chromatography-tandem mass spectrometry Anal Chem 77 757–763 Occurrence Handle15679341 Occurrence Handle10.1021/ac0489667 Occurrence Handle1:CAS:528:DC%2BD2cXhtFChsr%2FM

    Article  PubMed  CAS  Google Scholar 

  23. M Shiraki Y Shiraki C Aoki T Hosoi S Inoue M Kaneki Y Ouchi (1997) ArticleTitleAssociation of bone mineral density with apolipoprotein E phenotype J Bone Miner Res 12 1438–1445 Occurrence Handle9286760 Occurrence Handle10.1359/jbmr.1997.12.9.1438 Occurrence Handle1:CAS:528:DyaK2sXmt1WksLo%3D

    Article  PubMed  CAS  Google Scholar 

  24. HK Genant M Jergas L Palermo M Nevitt RS Valentin D Black SR Cummings (1996) ArticleTitleComparison of semiquantitative visual and quantitative morphometric assessment of prevalent and incident vertebral fractures in osteoporosis. The study of osteoporotic fractures Research Group J Bone Miner Res 11 984–996 Occurrence Handle8797120 Occurrence Handle1:STN:280:DyaK28zptVShtA%3D%3D Occurrence Handle10.1002/jbmr.5650110716

    Article  PubMed  CAS  Google Scholar 

  25. M Fukunaga T Nakamura M Shiraki T Kuroda H Ohta T Hosoi H Orimo (2004) ArticleTitleAbsolute height reduction and percent height ratio of the vertebral body in incident fracture in Japanese women J Bone Miner Metab 22 104–110 Occurrence Handle14999520 Occurrence Handle10.1007/s00774-003-0457-z

    Article  PubMed  Google Scholar 

  26. T Kanai T Takagi K Masuhiro M Nakamura M Iwata F Saji (1996) ArticleTitleSerum vitamin K level and bone mineral density in post-menopausal women Int J Gynecol Obstet 56 25–30 Occurrence Handle10.1016/S0020-7292(96)02790-7

    Article  Google Scholar 

  27. H Hagino K Yamamoto R Teshima H Kishimoto K Kuranobu T Nakamura (1990) ArticleTitleThe incidence of fractures of the proximal femur and the distal radius in Tottori prefecture, Japan Arch Orthop Trauma Surg 109 43–44 Occurrence Handle2344267 Occurrence Handle10.1007/BF00441909 Occurrence Handle1:STN:280:DyaK3c3mt1Citg%3D%3D

    Article  PubMed  CAS  Google Scholar 

  28. M Yamaguchi S Uchiyama Y Tsukamoto (2003) ArticleTitleInhibitory effect of menaquinone-7 (vitamin K2) on the bone-resorbing factors-induced bone resorption in elderly female rat femoral tissues in vitro Mol Cell Biochem 245 115–120 Occurrence Handle12708750 Occurrence Handle10.1023/A:1022818111655 Occurrence Handle1:CAS:528:DC%2BD3sXks12jsLs%3D

    Article  PubMed  CAS  Google Scholar 

  29. Y Tsukamoto H Ichise H Kakuda M Yamaguchi (2000) ArticleTitleIntake of fermented soybean (natto) increases circulating vitamin K2 (menaquinone-7) and gamma-carboxylated osteocalcin concentration in normal individuals J Bone Miner Metab 18 216–222 Occurrence Handle10874601 Occurrence Handle10.1007/s007740070023 Occurrence Handle1:CAS:528:DC%2BD3cXmsV2ksLc%3D

    Article  PubMed  CAS  Google Scholar 

  30. M Yamaguchi H Taguchi YH Gao A Igarashi Y Tsukamoto (1999) ArticleTitleEffect of vitamin K2 (menaquinone-7) in fermented soybean (natto) on bone loss in ovariectomized rats J Bone Miner Metab 17 23–29 Occurrence Handle10084398 Occurrence Handle10.1007/s007740050059 Occurrence Handle1:CAS:528:DyaK1MXislKltb4%3D

    Article  PubMed  CAS  Google Scholar 

  31. P Vergnaud P Garnero PJ Meunier G Breart K Kamihagi PD Delmas (1997) ArticleTitleUndercarboxylated osteocalcin measured with a specific immunoassay predicts hip fracture in elderly women: the EPIDOS Study J Clin Endocrinol Metab 82 719–724 Occurrence Handle9062471 Occurrence Handle10.1210/jc.82.3.719 Occurrence Handle1:CAS:528:DyaK2sXhsl2jsL4%3D

    Article  PubMed  CAS  Google Scholar 

  32. P Szulc MC Chapuy PJ Meunier PD Delmas (1996) ArticleTitleSerum undercarboxylated osteocalcin is a marker of the risk of hip fracture: a three year follow-up study Bone (NY) 18 487–488 Occurrence Handle1:STN:280:DyaK28zhvFWqsg%3D%3D

    CAS  Google Scholar 

  33. P Szulc M Arlot MC Chapuy F Duboeuf PJ Meunier PD Delmas (1994) ArticleTitleSerum undercarboxylated osteocalcin correlates with hip bone mineral density in elderly women J Bone Miner Res 9 1591–1595 Occurrence Handle7817805 Occurrence Handle1:CAS:528:DyaK2MXhslCltLw%3D

    PubMed  CAS  Google Scholar 

  34. P Szulc MC Chapuy PJ Meunier PD Delmas (1993) ArticleTitleSerum undercarboxylated osteocalcin is a marker of the risk of hip fracture in elderly women J Clin Invest 91 1769–1774 Occurrence Handle8473517 Occurrence Handle1:CAS:528:DyaK3sXktVKnsbw%3D Occurrence Handle10.1172/JCI116387

    Article  PubMed  CAS  Google Scholar 

  35. N Tsugawa M Shiraki M Suhara M Kamao K Tanaka T Okano (2006) ArticleTitleVitamin K status of healthy Japanese women: age-related vitamin K requirement for γ-carboxylation of osteocalcin Am J Clin Nutr 83 380–386 Occurrence Handle16469998 Occurrence Handle1:CAS:528:DC%2BD28Xhs1ehsbg%3D

    PubMed  CAS  Google Scholar 

  36. T Ichikawa K Horie-Inoue K Ikeda B Blumberg S Inoue (2006) ArticleTitleSteroid and xenobiotic receptor SXR mediates vitamin K2-activated transcription of extracellular matrix-related genes and collagen accumulation in osteoblastic cells J Biol Chem 281 16927–16934 Occurrence Handle16606623 Occurrence Handle10.1074/jbc.M600896200 Occurrence Handle1:CAS:528:DC%2BD28XlvVGksrY%3D

    Article  PubMed  CAS  Google Scholar 

  37. SL Booth I Golly JM Sacheck R Roubenoff GE Dallal K Hamada JB Blumberg (2004) ArticleTitleEffect of vitamin E supplementation on vitamin K status in adults with normal coagulation status Am J Clin Nutr 80 143–148 Occurrence Handle15213041 Occurrence Handle1:CAS:528:DC%2BD2cXltlKlt7Y%3D

    PubMed  CAS  Google Scholar 

  38. NC Binkley DC Krueger JA Engelke AL Foley JW Suttie (2000) ArticleTitleVitamin K supplementation reduces serum concentrations of under-gamma-carboxylated osteocalcin in healthy young and elderly adults Am J Clin Nutr 72 1523–1528 Occurrence Handle11101481 Occurrence Handle1:CAS:528:DC%2BD3cXosl2mt7w%3D

    PubMed  CAS  Google Scholar 

  39. NC Binkley DC Krueger TN Kawahara JA Engelke RJ Chappell JW Suttie (2002) ArticleTitleA high phylloquinone intake is required to achieve maximal osteocalcin gamma-carboxylation Am J Clin Nutr 76 1055–1060 Occurrence Handle12399278 Occurrence Handle1:CAS:528:DC%2BD38XosF2qs7s%3D

    PubMed  CAS  Google Scholar 

  40. AT Erkkila AH Lichtenstein GG Dolnikowski MA Grusak SM Jalbert KA Aquino JW Peterson SL Booth (2004) ArticleTitlePlasma transport of vitamin K in men using deuterium-labeled collard greens Metabolism 53 215–221 Occurrence Handle14767874 Occurrence Handle10.1016/j.metabol.2003.08.015 Occurrence Handle1:CAS:528:DC%2BD2cXptFSqsA%3D%3D

    Article  PubMed  CAS  Google Scholar 

  41. SR Beavan A Prentice DM Stirling B Dibba L Yan DJ Harrington MJ Shearer (2005) ArticleTitleEthnic differences in osteocalcin gamma-carboxylation, plasma phylloquinone (vitamin K1. and apolipoprotein E genotype Eur J Clin Nutr 59 72–81 Occurrence Handle15340366 Occurrence Handle10.1038/sj.ejcn.1602037 Occurrence Handle1:CAS:528:DC%2BD2cXhtVOnu7fN

    Article  PubMed  CAS  Google Scholar 

  42. Martini LA, Booth SL, Saltzman E, do Rosario Dias de Oliveira Latorre M, Wood RJ (2006) Dietary phylloquinone depletion and repletion in postmenopausal women: effects on bone and mineral metabolism. Osteoporos Int 17:929–935

    Google Scholar 

  43. M Kaneki Y Mizuno T Hosoi S Inoue S Hoshino M Akishita Y Akedo K Horiki T Nakamura M Shiraki (1995) ArticleTitleSerum concentration of vitamin K in elderly women with involutional osteoporosis Nippon Ronen Igakkai Zasshi 32 195–200 Occurrence Handle7596062 Occurrence Handle1:STN:280:DyaK2MzhvFSrtA%3D%3D

    PubMed  CAS  Google Scholar 

  44. M Shiraki Y Shiraki C Aoki M Miura (2000) ArticleTitleVitamin K2 (menatetrenone) effectively prevents fractures and sustains lumbar bone mineral density in osteoporosis J Bone Miner Res 15 515–521 Occurrence Handle10750566 Occurrence Handle10.1359/jbmr.2000.15.3.515 Occurrence Handle1:CAS:528:DC%2BD3cXitFaktrc%3D

    Article  PubMed  CAS  Google Scholar 

  45. M Kamao Y Suhara N Tsugawa T Okano (2005) ArticleTitleDetermination of plasma vitamin K by high-performance liquid chromatography with fluorescence detection using vitamin K analogs as internal standards J Chromatogr B Anal Technol Biomed Life Sci 816 41–48 Occurrence Handle10.1016/j.jchromb.2004.11.003 Occurrence Handle1:CAS:528:DC%2BD2MXmvFWqtQ%3D%3D

    Article  CAS  Google Scholar 

  46. M Shiraki T Kuroda T Nakamura M Fukunaga T Hosoi H Orimo K Makino (2006) ArticleTitleThe sample size required for intervention studies on fracture prevention can be decreased by using a bone resorption marker in the inclusion criteria: prospective study of a subset of the Nagano Cohort, on behalf of the Adequate Treatment of Osteoporosis (A-TOP). Research Group J Bone Miner Metab 24 219–225 Occurrence Handle16622735 Occurrence Handle10.1007/s00774-005-0675-7

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Toshio Okano.

About this article

Cite this article

Tsugawa, N., Shiraki, M., Suhara, Y. et al. Low plasma phylloquinone concentration is associated with high incidence of vertebral fracture in Japanese women. J Bone Miner Metab 26, 79–85 (2008). https://doi.org/10.1007/s00774-007-0790-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00774-007-0790-8

Key words

Navigation