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Issues related to the research on vitamin K supplementation and bone mineral density

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References

  1. 1.

    Demontiero O, Vidal C, Duque G. Aging and bone loss: new insights for the clinician. Ther Adv Musculoskelet Dis. 2012;4:61–76. https://doi.org/10.1177/1759720X11430858.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  2. 2.

    Ross AC, Manson JE, Abrams SA, Aloia JF, Brannon PM, Clinton SK, et al. The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know. J Clin Endocrinol Metab. 2011;96:53–58. https://doi.org/10.1210/jc.2010-2704.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  3. 3.

    Vermeer C. Vitamin K: the effect on health beyond coagulation - an overview. Food Nutr Res. 2012;56. https://doi.org/10.3402/fnr.v56i0.5329.

  4. 4.

    Hara K, Akiyama Y, Nakamura T, Murota S, Morita I. The inhibitory effect of vitamin K2 (menatetrenone) on bone resorption may be related to its side chain. Bone. 1995;16:179–84. https://doi.org/10.1016/8756-3282(94)00027-w.

    CAS  Article  PubMed  Google Scholar 

  5. 5.

    Tabb MM, Sun A, Zhou C, Grün F, Errandi J, Romero K, et al. Vitamin K2 regulation of bone homeostasis is mediated by the steroid and xenobiotic receptor SXR. J Biol Chem. 2003;278:43919–27. https://doi.org/10.1074/jbc.M303136200.

    CAS  Article  PubMed  Google Scholar 

  6. 6.

    Small RE. Uses and limitations of bone mineral density measurements in the management of osteoporosis. MedGenMed. 2005;7:3.

    PubMed  PubMed Central  Google Scholar 

  7. 7.

    Marshall D, Johnell O, Wedel H. Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures. BMJ. 1996;312:1254–9. https://doi.org/10.1136/bmj.312.7041.1254.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  8. 8.

    Hao G, Zhang B, Gu M, Chen C, Zhang Q, Zhang G, et al. Vitamin K intake and the risk of fractures: a meta-analysis. Medicine. 2017;96:e6725. https://doi.org/10.1097/MD.0000000000006725.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  9. 9.

    Cockayne S, Adamson J, Lanham-New S, Shearer MJ, Gilbody S, Torgerson DJ. Vitamin K and the prevention of fractures: systematic review and meta-analysis of randomized controlled trials. JAMA Intern Med. 2006;166:1256–61. https://doi.org/10.1001/archinte.166.12.1256.

    CAS  Article  Google Scholar 

  10. 10.

    Cummings SR, Black DM, Nevitt MC, Browner W, Cauley J, Ensrud K, et al. Bone density at various sites for prediction of hip fractures. The Study of Osteoporotic Fractures Research Group. Lancet. 1993;341:72–75. https://doi.org/10.1016/0140-6736(93)92555-8.

    CAS  Article  PubMed  Google Scholar 

  11. 11.

    Fang Y, Hu C, Tao X, Wan Y, Tao F. Effect of vitamin K on bone mineral density: a meta-analysis of randomized controlled trials. J Bone Min Metab. 2012;30:60–68. https://doi.org/10.1007/s00774-011-0287-3.

    CAS  Article  Google Scholar 

  12. 12.

    Huang ZB, Wan SL, Lu YJ, Ning L, Liu C, Fan SW. Does vitamin K2 play a role in the prevention and treatment of osteoporosis for postmenopausal women: a meta-analysis of randomized controlled trials. Osteoporos Int. 2015;26:1175–86. https://doi.org/10.1007/s00198-014-2989-6.

    CAS  Article  PubMed  Google Scholar 

  13. 13.

    Mott A, Bradley T, Wright K, Cockayne ES, Shearer MJ, Adamson J, et al. Effect of vitamin K on bone mineral density and fractures in adults: an updated systematic review and meta-analysis of randomised controlled trials. Osteoporos Int. 2019;30:1543–59. https://doi.org/10.1007/s00198-019-04949-0.

    CAS  Article  PubMed  Google Scholar 

  14. 14.

    Su S, He N, Men P, Song C, Zhai S. The efficacy and safety of menatetrenone in the management of osteoporosis: a systematic review and meta-analysis of randomized controlled trials. Osteoporos Int. 2019;30:1175–86. https://doi.org/10.1007/s00198-019-04853-7.

    CAS  Article  PubMed  Google Scholar 

  15. 15.

    Inoue T, Fujita T, Kishimoto H, Makino T, Nakamura T, Nakamura T, et al. Randomized controlled study on the prevention of osteoporotic fractures (OF study): a phase IV clinical study of 15-mg menatetrenone capsules. J Bone Min Metab. 2009;27:66–75. https://doi.org/10.1007/s00774-008-0008-8.

    CAS  Article  Google Scholar 

  16. 16.

    Tanaka S, Miyazaki T, Uemura Y, Miyakawa N, Gorai I, Nakamura T, et al. Comparison of concurrent treatment with vitamin K2 and risedronate compared with treatment with risedronate alone in patients with osteoporosis: Japanese Osteoporosis Intervention Trial-03. J Bone Min Metab. 2017;35:385–95. https://doi.org/10.1007/s00774-016-0768-5.

    CAS  Article  Google Scholar 

  17. 17.

    Kupferschmidt K. Tide of lies. Science. 2018;361:636–41. https://doi.org/10.1126/science.361.6403.636.

    CAS  Article  PubMed  Google Scholar 

  18. 18.

    Orimo H, Nakamura T, Hosoi T, Iki M, Uenishi K, Endo N, et al. Japanese 2011 guidelines for prevention and treatment of osteoporosis–executive summary. Arch Osteoporos. 2012;7:3–20. https://doi.org/10.1007/s11657-012-0109-9.

    Article  PubMed  PubMed Central  Google Scholar 

  19. 19.

    Boskey AL, Gadaleta S, Gundberg C, Doty SB, Ducy P, Karsenty G. Fourier transform infrared microspectroscopic analysis of bones of osteocalcin-deficient mice provides insight into the function of osteocalcin. Bone. 1998;23:187–96. https://doi.org/10.1016/s8756-3282(98)00092-1.

    CAS  Article  PubMed  Google Scholar 

  20. 20.

    Seeman E, Delmas PD. Bone quality–the material and structural basis of bone strength and fragility. N. Engl J Med. 2006;354:2250–61. https://doi.org/10.1056/NEJMra053077.

    CAS  Article  PubMed  Google Scholar 

  21. 21.

    Tranquilli Leali P, Doria C, Zachos A, Ruggiu A, Milia F, Barca F. Bone fragility: current reviews and clinical features. Clin Cases Min Bone Metab. 2009;6:109–13.

    Google Scholar 

  22. 22.

    Booth SL, Broe KE, Gagnon DR, Tucker KL, Hannan MT, McLean RR, et al. Vitamin K intake and bone mineral density in women and men. Am J Clin Nutr. 2003;77:512–6. https://doi.org/10.1093/ajcn/77.2.512.

    CAS  Article  PubMed  Google Scholar 

  23. 23.

    Binkley N, Harke J, Krueger D, Engelke J, Vallarta-Ast N, Gemar D, et al. Vitamin K treatment reduces undercarboxylated osteocalcin but does not alter bone turnover, density, or geometry in healthy postmenopausal North American women. J Bone Min Res. 2009;24:983–91. https://doi.org/10.1359/jbmr.081254.

    CAS  Article  Google Scholar 

  24. 24.

    Cheung AM, Tile L, Lee Y, Tomlinson G, Hawker G, Scher J, et al. Vitamin K supplementation in postmenopausal women with osteopenia (ECKO trial): a randomized controlled trial. PLoS Med. 2008;5:e196. https://doi.org/10.1371/journal.pmed.0050196.

    CAS  Article  PubMed  Google Scholar 

  25. 25.

    Bolton-Smith C, McMurdo ME, Paterson CR, Mole PA, Harvey JM, Fenton ST, et al. Two-year randomized controlled trial of vitamin K1 (phylloquinone) and vitamin D3 plus calcium on the bone health of older women. J Bone Min Res. 2007;22:509–19. https://doi.org/10.1359/jbmr.070116.

    CAS  Article  Google Scholar 

  26. 26.

    Knapen MH, Schurgers LJ, Vermeer C. Vitamin K2 supplementation improves hip bone geometry and bone strength indices in postmenopausal women. Osteoporos Int. 2007;18:963–72. https://doi.org/10.1007/s00198-007-0337-9.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  27. 27.

    Ronn SH, Harslof T, Pedersen SB, Langdahl BL. Vitamin K2 (menaquinone-7) prevents age-related deterioration of trabecular bone microarchitecture at the tibia in postmenopausal women. Eur J Endocrinol. 2016;175:541–9. https://doi.org/10.1530/EJE-16-0498.

    CAS  Article  PubMed  Google Scholar 

  28. 28.

    Watts NB. Bone quality: getting closer to a definition. J Bone Min Res. 2002;17:1148–50. https://doi.org/10.1359/jbmr.2002.17.7.1148.

    Article  Google Scholar 

  29. 29.

    Institute of Medicine (US) Panel on Micronutrients. Dietary reference intakes for vitamin A, vitamin K, arsenic, boron, chromium, copper, iodine, iron, manganese, molybdenum, nickel, silicon, vanadium, and zinc. Washington (DC): National Academies Press; 2001. https://www.ncbi.nlm.nih.gov/books/NBK222310/: https://doi.org/10.17226/10026.

  30. 30.

    Braam LA, Knapen MH, Geusens P, Brouns F, Hamulyak K, Gerichhausen MJ, et al. Vitamin K1 supplementation retards bone loss in postmenopausal women between 50 and 60 years of age. Calcif Tissue Int. 2003;73:21–26. https://doi.org/10.1007/s00223-002-2084-4.

    CAS  Article  PubMed  Google Scholar 

  31. 31.

    Kanellakis S, Moschonis G, Tenta R, Schaafsma A, van den Heuvel EG, Papaioannou N, et al. 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. 2012;90:251–62. https://doi.org/10.1007/s00223-012-9571-z.

    CAS  Article  PubMed  Google Scholar 

  32. 32.

    Koitaya N, Sekiguchi M, Tousen Y, Nishide Y, Morita A, Yamauchi J, et al. Low-dose vitamin K2 (MK-4) supplementation for 12 months improves bone metabolism and prevents forearm bone loss in postmenopausal Japanese women. J Bone Min Metab. 2014;32:142–50. https://doi.org/10.1007/s00774-013-0472-7.

    CAS  Article  Google Scholar 

  33. 33.

    Booth SL, Dallal G, Shea MK, Gundberg C, Peterson JW, Dawson-Hughes B. Effect of vitamin K supplementation on bone loss in elderly men and women. J Clin Endocrinol Metab. 2008;93:1217–23. https://doi.org/10.1210/jc.2007-2490.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  34. 34.

    Mayo Clinic Laboratories. Test definition: VITK1. https://www.mayocliniclabs.com/test-catalog/download-setup.php?format=pdf&unit_code=42364. Accessed 4 May 2021.

  35. 35.

    Mott A, Bradley T, Wright K, Cockayne ES, Shearer MJ, Adamson J, et al. Correction to Effect of vitamin K on bone mineral density and fractures in adults: an updated systematic review and meta-analysis of randomised controlled trials. Osteoporos Int. 2020;31:2269–70. https://doi.org/10.1007/s00198-020-05586-8.

    CAS  Article  PubMed  Google Scholar 

  36. 36.

    Suresh K. An overview of randomization techniques: an unbiased assessment of outcome in clinical research. J Hum Reprod Sci. 2011;4:8–11. https://doi.org/10.4103/0974-1208.82352.

    Article  PubMed  PubMed Central  Google Scholar 

  37. 37.

    Karanicolas PJ, Farrokhyar F, Bhandari M. Practical tips for surgical research: blinding: who, what, when, why, how? Can J Surg. 2010;53:345–8.

    PubMed  PubMed Central  Google Scholar 

  38. 38.

    Je SH, Joo NS, Choi BH, Kim KM, Kim BT, Park SB, et al. Vitamin K supplement along with vitamin D and calcium reduced serum concentration of undercarboxylated osteocalcin while increasing bone mineral density in Korean postmenopausal women over sixty-years-old. J Korean Med Sci. 2011;26:1093–8. https://doi.org/10.3346/jkms.2011.26.8.1093.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  39. 39.

    Tavakoli MB, Salamat MR, Tavakoli M. Comparative study of the density of L2, L3, and L4 vertebrae in menopausal women aged over 50 years with osteoporosis. J Educ Health Promot. 2015;4:43. https://doi.org/10.4103/2277-9531.157229.

    Article  PubMed  PubMed Central  Google Scholar 

  40. 40.

    Akbari S, Rasouli-Ghahroudi AA. Vitamin K and bone metabolism: a review of the latest evidence in preclinical studies. BioMed Res Int. 2018;2018:4629383. https://doi.org/10.1155/2018/4629383.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  41. 41.

    Ichikawa T, Horie-Inoue K, Ikeda K, Blumberg B, Inoue S. Steroid and xenobiotic receptor SXR mediates vitamin K2-activated transcription of extracellular matrix-related genes and collagen accumulation in osteoblastic cells. J Biol Chem. 2006;281:16927–34. https://doi.org/10.1074/jbc.M600896200.

    CAS  Article  PubMed  Google Scholar 

  42. 42.

    Sroga GE, Vashishth D. Effects of bone matrix proteins on fracture and fragility in osteoporosis. Curr Osteoporos Rep. 2012;10:141–50. https://doi.org/10.1007/s11914-012-0103-6.

    Article  PubMed  PubMed Central  Google Scholar 

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YZ conceived the study and drafted the manuscript. MKS critically reviewed and revised the manuscript. SEJ critically reviewed and revised the manuscript. MED critically reviewed and revised the manuscript. KK conceived the study and critically reviewed and revised the manuscript.

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Correspondence to Ka Kahe.

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Zhang, Y., Shea, M.K., Judd, S.E. et al. Issues related to the research on vitamin K supplementation and bone mineral density. Eur J Clin Nutr (2021). https://doi.org/10.1038/s41430-021-00941-2

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