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Osteoporosis International

, Volume 30, Issue 8, pp 1543–1559 | Cite as

Effect of vitamin K on bone mineral density and fractures in adults: an updated systematic review and meta-analysis of randomised controlled trials

  • A. MottEmail author
  • T. Bradley
  • K. Wright
  • E. S. Cockayne
  • M. J. Shearer
  • J. Adamson
  • S. A. Lanham-New
  • D. J. Torgerson
Review Article

Abstract

Summary

Vitamin K may affect bone mineral density and fracture incidence. Since publication of a previous systematic review the integrity of some of the previous evidence has been questioned and further trials have been published. Therefore an update to the systematic review was required.

Introduction

This systematic review was designed to assess the effectiveness of oral vitamin K supplementation for increasing bone mineral density and reducing fractures in adults.

Methods

MEDLINE, EMBASE, CENTRAL, CINAHL, clinicaltrials.gov, and WHO-ICTRP were searched for eligible trials. Randomised controlled trials assessing oral vitamin K supplementation that assessed bone mineral density or fractures in adult populations were included. A total of 36 studies were identified. Two independent reviewers extracted data using a piloted extraction form.

Results

For post-menopausal or osteoporotic patients, meta-analysis showed that the odds of any clinical fracture were lower for vitamin K compared to controls (OR, 0.72, 95%CI 0.55 to 0.95). Restricting the analysis to low risk of bias trials reduced the OR to 0.76 (95%CI, 0.58 to 1.01). There was no difference in vertebral fractures between the groups (OR 0.96, 95%CI 0.83 to 1.11). In the bone mineral density meta-analysis, percentage change from baseline at the lumbar spine was higher at 1 year (MD 0.93, 95%, CI − 0.02 to 1.89) and 2 years (MD 1.63%, 95%CI 0.10 to 3.16) for vitamin K compared to controls; however, removing trials at high risk of bias tended to result in smaller differences that were not statistically significant. At 6 months, it was higher in the hip (MD 0.42%, 95%CI 0.01 to 0.83) and femur (MD 0.29%, 95%CI 0.17 to 0.42). There was no significant difference at other anatomical sites.

Conclusions

For post-menopausal or osteoporotic patients, there is no evidence that vitamin K affects bone mineral density or vertebral fractures; it may reduce clinical fractures; however, the evidence is insufficient to confirm this. There are too few trials to draw conclusions for other patient groups.

Keywords

Bone health Bone mineral density Fracture Osteoporosis Systematic review Vitamin K 

Notes

Funding

There was no funding for this systematic review.

Compliance with ethical standards

Conflicts of interest

None.

Supplementary material

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References

  1. 1.
    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(12):1256–1261.  https://doi.org/10.1001/archinte.166.12.1256 CrossRefGoogle Scholar
  2. 2.
    Torgerson DJ (2018) Caution to readers about systematic review on vitamin K and prevention of fractures that included problematic trials. JAMA Intern Med 178(6):863–864.  https://doi.org/10.1001/jamainternmed.2018.1127 CrossRefGoogle Scholar
  3. 3.
    Bolland MJ, Avenell A, Gamble GD, Grey A (2016) Systematic review and statistical analysis of the integrity of 33 randomized controlled trials. Neurology 87(23):2391–2402.  https://doi.org/10.1212/WNL.0000000000003387 CrossRefGoogle Scholar
  4. 4.
    Sato Y, Honda Y, Iwamoto J (2018) RETRACTED: etidronate for fracture prevention in amyotrophic lateral sclerosis: a randomized controlled trial. Bone 106:214.  https://doi.org/10.1016/j.bone.2017.10.008 CrossRefGoogle Scholar
  5. 5.
    Booth SL (2009) Roles for vitamin K beyond coagulation. Annu Rev Nutr 29:89–110.  https://doi.org/10.1146/annurev-nutr-080508-141217 CrossRefGoogle Scholar
  6. 6.
    Bügel S (2008) Vitamin K and bone health in adult humans. 78:393–416.  https://doi.org/10.1016/s0083-6729(07)00016-7
  7. 7.
    Gundberg CM, Lian JB, Booth SL (2012) Vitamin K-dependent carboxylation of osteocalcin: friend or foe? Adv Nutr 3(2):149–157.  https://doi.org/10.3945/an.112.001834 CrossRefGoogle Scholar
  8. 8.
    Liu G, Peacock M (1998) Age-related changes in serum undercarboxylated osteocalcin and its relationships with bone density, bone quality, and hip fracture. Calcif Tissue Int 62(4):286–289.  https://doi.org/10.1007/s002239900432 CrossRefGoogle Scholar
  9. 9.
    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(4):1769–1774.  https://doi.org/10.1172/JCI116387 CrossRefGoogle Scholar
  10. 10.
    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(10):1591–1595.  https://doi.org/10.1002/jbmr.5650091012 CrossRefGoogle Scholar
  11. 11.
    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(3):719–724.  https://doi.org/10.1210/jcem.82.3.3805 Google Scholar
  12. 12.
    Booth SL, Broe KE, Peterson JW, Cheng DM, Dawson-Hughes B, Gundberg CM, Cupples LA, Wilson PW, Kiel DP (2004) Associations between vitamin K biochemical measures and bone mineral density in men and women. J Clin Endocrinol Metab 89(10):4904–4909.  https://doi.org/10.1210/jc.2003-031673 CrossRefGoogle Scholar
  13. 13.
    Marshall D, Johnell O, Wedel H (1996) Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures. Bmj 312(7041):1254–1259.  https://doi.org/10.1136/bmj.312.7041.1254 CrossRefGoogle Scholar
  14. 14.
    Hao G, Zhang B, Gu M, Chen C, Zhang Q, Zhang G, Cao X (2017) Vitamin K intake and the risk of fractures: a meta-analysis. Medicine (Baltimore) 96(17):e6725.  https://doi.org/10.1097/MD.0000000000006725 CrossRefGoogle Scholar
  15. 15.
    Garner P, Hopewell S, Chandler J, MacLehose H, Schunemann HJ, Akl EA, Beyene J, Chang S, Churchill R, Dearness K, Guyatt G, Lefebvre C, Liles B, Marshall R, Martinez Garcia L, Mavergames C, Nasser M, Qaseem A, Sampson M, Soares-Weiser K, Takwoingi Y, Thabane L, Trivella M, Tugwell P, Welsh E, Wilson EC, Schunemann HJ, Panel for updating guidance for systematic r (2016) When and how to update systematic reviews: consensus and checklist. BMJ 354:i3507.  https://doi.org/10.1136/bmj.i3507 CrossRefGoogle Scholar
  16. 16.
    RETRACTION: risedronate therapy for prevention of hip fracture after stroke in elderly women; risedronate therapy for prevention of hip fracture after stroke in elderly women. Reply from the Authors (2016). Neurology 87 (2):239.  https://doi.org/10.1212/WNL.0000000000002788
  17. 17.
    Kupferschmidt K (2018) Researcher at the center of an epic fraud remains an enigma to those who exposed him. Science.  https://doi.org/10.1126/science.aav1079
  18. 18.
    Poisot T (2011) The digitize package: extracting numerical data from scatterplots. R J 3(1):25–26CrossRefGoogle Scholar
  19. 19.
    Higgins JP, Altman DG, Gotzsche PC, Juni P, Moher D, Oxman AD, Savovic J, Schulz KF, Weeks L, Sterne JA, Cochrane Bias Methods G, Cochrane Statistical Methods G (2011) The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ 343:d5928.  https://doi.org/10.1136/bmj.d5928 CrossRefGoogle Scholar
  20. 20.
    Hicks A, Fairhurst C, Torgerson DJ (2018) A simple technique investigating baseline heterogeneity helped to eliminate potential bias in meta-analyses. J Clin Epidemiol 95:55–62.  https://doi.org/10.1016/j.jclinepi.2017.10.001 CrossRefGoogle Scholar
  21. 21.
    Higgins JPT, Green S (2011) Cochrane handbook for systematic reviews of interventions, vol 5.1.0.  https://doi.org/10.1002/9780470712184
  22. 22.
    Sterne JA, Sutton AJ, Ioannidis JP, Terrin N, Jones DR, Lau J, Carpenter J, Rucker G, Harbord RM, Schmid CH, Tetzlaff J, Deeks JJ, Peters J, Macaskill P, Schwarzer G, Duval S, Altman DG, Moher D, Higgins JP (2011) Recommendations for examining and interpreting funnel plot asymmetry in meta-analyses of randomised controlled trials. BMJ 343:d4002.  https://doi.org/10.1136/bmj.d4002 CrossRefGoogle Scholar
  23. 23.
    Viechtbauer W (2010) Conducting meta-analyses in R with the metafor package. J Stat Softw 36(3).  https://doi.org/10.18637/jss.v036.i03
  24. 24.
    R Development Core Team (2017) R: a language and environment for statistical computing. 3.4.0 edn. R Foundation for Statistical Computing, ViennaGoogle Scholar
  25. 25.
    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(4):1217–1223.  https://doi.org/10.1210/jc.2007-2490 CrossRefGoogle Scholar
  26. 26.
    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(4):509–519.  https://doi.org/10.1359/jbmr.070116 CrossRefGoogle Scholar
  27. 27.
    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(6):983–991.  https://doi.org/10.1359/jbmr.081254 CrossRefGoogle Scholar
  28. 28.
    Braam LA, Knapen MH, Geusens P, Brouns F, Vermeer C (2003) Factors affecting bone loss in female endurance athletes: a two-year follow-up study. Am J Sports Med 31(6):889–895.  https://doi.org/10.1177/03635465030310062601 CrossRefGoogle Scholar
  29. 29.
    Braam LAJLM, Knapen MHJ, Geusens P, Brouns F, Hamulyk K, Gerichhausen MJW, Vermeer C (2003) Vitamin K1 supplementation retards bone loss in postmenopausal women between 50 and 60 years of age. Calcif Tissue Int 73(1):21–26.  https://doi.org/10.1007/s00223-002-2084-4 CrossRefGoogle Scholar
  30. 30.
    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 Med 5(10):e196.  https://doi.org/10.1371/journal.pmed.0050196 CrossRefGoogle Scholar
  31. 31.
    Emaus N, Gjesdal CG, Almas B, Christensen M, Grimsgaard AS, Berntsen GK, Salomonsen L, Fonnebo V (2010) Vitamin K2 supplementation does not influence bone loss in early menopausal women: a randomised double-blind placebo-controlled trial. Osteoporos Int 21(10):1731–1740.  https://doi.org/10.1007/s00198-009-1126-4 CrossRefGoogle Scholar
  32. 32.
    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(4):458–464.  https://doi.org/10.1097/TP.0b013e3181c46b69 CrossRefGoogle Scholar
  33. 33.
    Fulton RL, McMurdo ME, Hill A, Abboud RJ, Arnold GP, Struthers AD, Khan F, Vermeer C, Knapen MH, Drummen NE, Witham MD (2016) Effect of vitamin K on vascular health and physical function in older people with vascular disease—a randomised controlled trial. J Nutr Health Aging 20(3):325–333.  https://doi.org/10.1007/s12603-015-0619-4 CrossRefGoogle Scholar
  34. 34.
    Gleeson D, Hodges S, Rigney E, Blumsohn A, Hannon R, Peel N, Eastell R (2003) 740 placebo-controlled trial of vitamin K supplementation on bone mineral density in primary biliary cirrhosis (PBC). Hepatology 38:516–516.  https://doi.org/10.1016/s0270-9139(03)80782-6 CrossRefGoogle Scholar
  35. 35.
    Hirao M, Hashimoto J, Ando W, Ono T, Yoshikawa H (2008) Response of serum carboxylated and undercarboxylated osteocalcin to alendronate monotherapy and combined therapy with vitamin K2 in postmenopausal women. J Bone Miner Metab 26(3):260–264.  https://doi.org/10.1007/s00774-007-0823-3 CrossRefGoogle Scholar
  36. 36.
    Hozuki T, Imai T, Tsuda E, Matsumura A, Yamamoto D, Toyoshima T, Suzuki S, Yamauchi R, Hayashi T, Hisahara S, Shimohama S (2010) Response of serum carboxylated and undercarboxylated osteocalcin to risedronate monotherapy and combined therapy with vitamin K2 in corticosteroid-treated patients: a pilot study. Intern Med 49(5):371–376.  https://doi.org/10.2169/internalmedicine.49.2551 CrossRefGoogle Scholar
  37. 37.
    Inoue K, Hamano T, Nango N, Matsui I, Tomida K, Mikami S, Fujii N, Nakano C, Obi Y, Shimomura A, Kusunoki Y, Rakugi H, Isaka Y, Tsubakihara Y (2014) Multidetector-row computed tomography is useful to evaluate the therapeutic effects of bisphosphonates in glucocorticoid-induced osteoporosis. J Bone Miner Metab 32(3):271–280.  https://doi.org/10.1007/s00774-013-0485-2 CrossRefGoogle Scholar
  38. 38.
    Inoue T, Fujita T, Kishimoto H, Makino T, Nakamura T, Nakamura T, Sato T, Yamazaki K (2009) Randomized controlled study on the prevention of osteoporotic fractures (OF study): a phase IV clinical study of 15-mg menatetrenone capsules. J Bone Miner Metab 27(1):66–75.  https://doi.org/10.1007/s00774-008-0008-8 CrossRefGoogle Scholar
  39. 39.
    Ishida Y, Kawai S (2004) Comparative efficacy of hormone replacement therapy, etidronate, calcitonin, alfacalcidol, and vitamin K in postmenopausal women with osteoporosis: the Yamaguchi Osteoporosis Prevention Study. Am J Med 117(8):549–555.  https://doi.org/10.1016/j.amjmed.2004.05.019 CrossRefGoogle Scholar
  40. 40.
    Iwamoto I, Kosha S, Noguchi S-i, Murakami M, Fujino T, Douchi T, Nagata Y (1999) A longitudinal study of the effect of vitamin K2 on bone mineral density in postmenopausal women a comparative study with vitamin D3 and estrogen–progestin therapy. Maturitas 31(2):161–164.  https://doi.org/10.1016/s0378-5122(98)00114-5 CrossRefGoogle Scholar
  41. 41.
    Je SH, Joo NS, Choi BH, Kim KM, Kim BT, Park SB, Cho DY, Kim KN, Lee DJ (2011) 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 26(8):1093–1098.  https://doi.org/10.3346/jkms.2011.26.8.1093 CrossRefGoogle Scholar
  42. 42.
    Jiang Y, Zhang ZL, Zhang ZL, Zhu HM, Wu YY, Cheng Q, Wu FL, Xing XP, Liu JL, Yu W, Meng XW (2014) Menatetrenone versus alfacalcidol in the treatment of Chinese postmenopausal women with osteoporosis: a multicenter, randomized, double-blinded, double-dummy, positive drug-controlled clinical trial. Clin Interv Aging 9:121–127.  https://doi.org/10.2147/CIA.S54107 Google Scholar
  43. 43.
    Jokar M, Mirfeizi Z, Esmaili HMK (2016) Effect of vitamin K and alendronate combination treatment on bone mineral density of postmenopausal osteoporosis patients: a pilot study. Patient Saf Qual Improv 4(1):320–333.  https://doi.org/10.22038/psj.2016.6288 Google Scholar
  44. 44.
    Retraction blues (2013) Nat Med 19(12):1547–1548.  https://doi.org/10.1038/nm.3426 CrossRefGoogle Scholar
  45. 45.
    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(4):251–262.  https://doi.org/10.1007/s00223-012-9571-z CrossRefGoogle Scholar
  46. 46.
    Kasukawa Y, Miyakoshi N, Ebina T, Aizawa T, Hongo M, Nozaka K, Ishikawa Y, Saito H, Chida S, Shimada Y (2014) Effects of risedronate alone or combined with vitamin K2 on serum undercarboxylated osteocalcin and osteocalcin levels in postmenopausal osteoporosis. J Bone Miner Metab 32(3):290–297.  https://doi.org/10.1007/s00774-013-0490-5 CrossRefGoogle Scholar
  47. 47.
    Knapen MH, Drummen NE, Smit E, Vermeer C, Theuwissen E (2013) Three-year low-dose menaquinone-7 supplementation helps decrease bone loss in healthy postmenopausal women. Osteoporos Int 24(9):2499–2507.  https://doi.org/10.1007/s00198-013-2325-6 CrossRefGoogle Scholar
  48. 48.
    Knapen MH, Schurgers LJ, Vermeer C (2007) Vitamin K2 supplementation improves hip bone geometry and bone strength indices in postmenopausal women. Osteoporos Int 18(7):963–972.  https://doi.org/10.1007/s00198-007-0337-9 CrossRefGoogle Scholar
  49. 49.
    Koitaya N, Sekiguchi M, Tousen Y, Nishide Y, Morita A, Yamauchi J, Gando Y, Miyachi M, Aoki M, Komatsu M, Watanabe F, Morishita K, Ishimi Y (2014) Low-dose vitamin K2 (MK-4) supplementation for 12 months improves bone metabolism and prevents forearm bone loss in postmenopausal Japanese women. J Bone Miner Metab 32(2):142–150.  https://doi.org/10.1007/s00774-013-0472-7 CrossRefGoogle Scholar
  50. 50.
    Moschonis G, Kanellakis S, Papaioannou N, Schaafsma A, Manios Y (2011) Possible site-specific effect of an intervention combining nutrition and lifestyle counselling with consumption of fortified dairy products on bone mass: the Postmenopausal Health Study II. J Bone Miner Metab 29(4):501–506.  https://doi.org/10.1007/s00774-010-0256-2 CrossRefGoogle Scholar
  51. 51.
    Nishiguchi S, Shimoi S, Kurooka H, Tamori A, Habu D, Takeda T, Ochi H (2001) Randomized pilot trial of vitamin K2 for bone loss in patients with primary biliary cirrhosis. J Hepatol 35(4):543–545.  https://doi.org/10.1016/s0168-8278(01)00133-7 CrossRefGoogle Scholar
  52. 52.
    O'Connor EM, Grealy G, McCarthy J, Desmond A, Craig O, Shanahan F, Cashman KD (2014) Effect of phylloquinone (vitamin K1) supplementation for 12 months on the indices of vitamin K status and bone health in adult patients with Crohn’s disease. Br J Nutr 112(7):1163–1174.  https://doi.org/10.1017/S0007114514001913 CrossRefGoogle Scholar
  53. 53.
    Ronn SH, Harslof T, Pedersen SB, Langdahl BL (2016) Vitamin K2 (menaquinone-7) prevents age-related deterioration of trabecular bone microarchitecture at the tibia in postmenopausal women. Eur J Endocrinol 175(6):541–549.  https://doi.org/10.1530/EJE-16-0498 CrossRefGoogle Scholar
  54. 54.
    Purwosunu Y, Muharram RIA, Reksoprodjo S, Sekizawa A (2006) Vitamin K2 treatment for postmenopausal osteoporosis in Indonesia. J Obstet Gynaecol Res 32(2):230–234.  https://doi.org/10.1111/j.1447-0756.2006.00386.x CrossRefGoogle Scholar
  55. 55.
    Sasaki N, Kusano E, Takahashi H, Ando Y, Yano K, Tsuda E, Asano Y (2005) Vitamin K2 inhibits glucocorticoid-induced bone loss partly by preventing the reduction of osteoprotegerin (OPG). J Bone Miner Metab 23(1):41–47.  https://doi.org/10.1007/s00774-004-0539-6 CrossRefGoogle Scholar
  56. 56.
    Shiomi S, Nishiguchi S, Kubo S, Tamori A, Habu D, Takeda T, Ochi H (2002) Vitamin K2 (menatetrenone) for bone loss in patients with cirrhosis of the liver. Am J Gastroenterol 97(4):978–981.  https://doi.org/10.1111/j.1572-0241.2002.05618.x CrossRefGoogle Scholar
  57. 57.
    Shiraki M, Itabashi A (2009) Short-term menatetrenone therapy increases gamma-carboxylation of osteocalcin with a moderate increase of bone turnover in postmenopausal osteoporosis: a randomized prospective study. J Bone Miner Metab 27(3):333–340.  https://doi.org/10.1007/s00774-008-0034-6 CrossRefGoogle Scholar
  58. 58.
    Shiraki M, Shiraki Y, Aoki C, Miura M (2000) Vitamin K2 (menatetrenone) effectively prevents fractures and sustains lumbar bone mineral density in osteoporosis. J Bone Miner Res 15(3):515–521.  https://doi.org/10.1359/jbmr.2000.15.3.515 CrossRefGoogle Scholar
  59. 59.
    Somekawa Y, Chigughi M, Harada M, Ishibashi T (1999) Use of vitamin K2 (menatetrenone) and 1,25-dihydroxyvitamin D3 in the prevention of bone loss induced by leuprolide. J Clin Endocrinol Metab 84(8):2700–2704.  https://doi.org/10.1210/jcem.84.8.5920 Google Scholar
  60. 60.
    Tanaka S, Miyazaki T, Uemura Y, Miyakawa N, Gorai I, Nakamura T, Fukunaga M, Ohashi Y, Ohta H, Mori S, Hagino H, Hosoi T, Sugimoto T, Itoi E, Orimo H, Shiraki M (2017) 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 Miner Metab 35(4):385–395.  https://doi.org/10.1007/s00774-016-0768-5 CrossRefGoogle Scholar
  61. 61.
    Ushiroyama T, Ikeda A, Ueki M (2002) Effect of continuous combined therapy with vitamin K2 and vitamin D3 on bone mineral density and coagulofibrinolysis function in postmenopausal women. Maturitas 41(3):211–221.  https://doi.org/10.1016/s0378-5122(01)00275-4 CrossRefGoogle Scholar
  62. 62.
    Volpe SL, Leung MM, Giordano H (2008) Vitamin K supplementation does not significantly impact bone mineral density and biochemical markers of bone in pre- and perimenopausal women. Nutr Res 28(9):577–582.  https://doi.org/10.1016/j.nutres.2008.06.006 CrossRefGoogle Scholar
  63. 63.
    Yuko M, Hitoshi S, Masao K, Hiromitsu F, Satoshi M, Takashi K, Yasuhiko K, Tatsuya A, Teruo H, Katsuhiko A, Yasuhiko T (2014) Poster session-PS3-036 risedronate combined with menatetrenone may prevent glucocorticoid-induced osteoporosis in patients with chronic glomerulonephritis. Nephrology 19:77–202.  https://doi.org/10.1111/nep.12237 CrossRefGoogle Scholar
  64. 65.
    Holden RM, Booth SL, Day AG, Clase CM, Zimmerman D, Moist L, Shea MK, McCabe KM, Jamal SA, Tobe S, Weinstein J, Madhumathi R, Adams MA, Heyland DK (2015) Inhibiting the progression of arterial calcification with vitamin K in HemoDialysis patients (iPACK-HD) trial: rationale and study design for a randomized trial of vitamin K in patients with end stage kidney disease. Can J Kidney Health Dis 2:17.  https://doi.org/10.1186/s40697-015-0053-x CrossRefGoogle Scholar
  65. 66.
    Hampson G (2015) Vitamin K as additive treatment in osteoporosis. https://ClinicalTrials.gov/show/NCT01232647
  66. 67.
    Genant HK, Li J, Wu CY, JA S (2000) Vertebral fractures in osteoporosis: a new method for clinical assessment. J Clin Densitom 3:281–290CrossRefGoogle Scholar
  67. 68.
    Fukunaga M, Nakamura T, Shiraki M, Kuroda T, Ohta H, Hosoi T, Orimo H (2004) Absolute height reduction and percent height ratio of the vertebral body in incident fracture in Japanese women. J Bone Miner Metab 22(2):104–110.  https://doi.org/10.1007/s00774-003-0457-z CrossRefGoogle Scholar
  68. 69.
    Tai V, Leung W, Grey A, Reid IR, Bolland MJ (2015) Calcium intake and bone mineral density: systematic review and meta-analysis. BMJ 351:h4183.  https://doi.org/10.1136/bmj.h4183 CrossRefGoogle Scholar
  69. 70.
    Veronese N, Bano G, Bertozzo G, Granziera S, Solmi M, Manzato E, Sergi G, Cohen AT, Correll CU (2015) Vitamin K antagonists’ use and fracture risk: results from a systematic review and meta-analysis. J Thromb Haemost 13(9):1665–1675.  https://doi.org/10.1111/jth.13052 CrossRefGoogle Scholar
  70. 71.
    Bach AU, Anderson SA, Foley AL, Williams EC, Suttie JW (1996) Assessment of vitamin K status in human subjects administered “minidose” warfarin. Am J Clin Nutr 64(6):894–902.  https://doi.org/10.1093/ajcn/64.6.894 CrossRefGoogle Scholar
  71. 72.
    Huang ZB, Wan SL, Lu YJ, Ning L, Liu C, Fan SW (2015) 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 26(3):1175–1186.  https://doi.org/10.1007/s00198-014-2989-6 CrossRefGoogle Scholar
  72. 73.
    Su S, He N, Men P, Song C, Zhai S (2019) The efficacy and safety of menatetrenone in the management of osteoporosis: a systematic review and meta-analysis of randomized controlled trials. Osteoporos Int.  https://doi.org/10.1007/s00198-019-04853-7
  73. 74.
    Newman P, Shearer MJ (2008) Metabolism and cell biology of vitamin K. Thromb Haemost 100(10):530–547.  https://doi.org/10.1160/th08-03-0147 CrossRefGoogle Scholar
  74. 75.
    Ballane G, Cauley JA, Luckey MM, El-Hajj Fuleihan G (2017) Worldwide prevalence and incidence of osteoporotic vertebral fractures. Osteoporos Int 28(5):1531–1542.  https://doi.org/10.1007/s00198-017-3909-3 CrossRefGoogle Scholar
  75. 76.
    Shea MK, Booth SL (2016) Concepts and controversies in evaluating vitamin K status in population-based studies. Nutrients 8(1).  https://doi.org/10.3390/nu8010008

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2019

Authors and Affiliations

  1. 1.York Trials Unit, Department of Health SciencesUniversity of YorkYorkUK
  2. 2.Chesterfield HospitalCalowUK
  3. 3.Centre for Reviews & DisseminationUniversity of YorkYorkUK
  4. 4.Centre for Haemostasis and ThrombosisGuy’s and St Thomas’ NHS TrustLondonUK
  5. 5.Institute of Health & SocietyNewcastle UniversityNewcastle upon TyneUK
  6. 6.Nutritional Sciences Department, School of Biosciences and Medicine, Faculty of Health and Medical SciencesUniversity of SurreyGuildfordUK

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