Vitamin Status and Mineralized Tissue Formation

  • Eijiro JimiEmail author
Oral Disease and Nutrition (F Nishimura, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Oral Disease and Nutrition


Purpose of the Review

Vitamins play important roles in bone health, and vitamin supplementation has been recommended to prevent osteoporosis and to reduce fracture risk in the elderly. However, the benefits of vitamin intake for bone health are still controversial. The aim of the review is to examine the relationship between vitamins and bone health and how vitamins function in osteoblasts and osteoclasts.

Recent Findings

A broad literature search with the PubMed database was performed. The results of human clinical studies are inconsistent due to differences in the study design, race, genetic factors, and the population. Vitamin K, E, or C intake seems to benefit for bone health as well as vitamin D. Recent findings did not support the benefit of the vitamin B complex for bone health. Furthermore, both the excess and deficiency of vitamin A might be involved in compromised bone health.


The well-balanced and adequate amounts of vitamins should be ensured to prevent adverse effects on bone health.


Vitamins Bone Fracture risk Osteoporosis Osteoblasts Osteoclasts 



This study was supported by the research grant for OBT Research Center from the Kyushu University.

Compliance with Ethical Standards

Conflict of Interest

Eijiro Jimi declares no conflicts of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Aubin JE, Triffitt JT. Mesenchymal stem cells and osteoblast differentiation. In: Bilezikian JP, Raisz LG, Rodan GA, editors. Principles of bone biology. 2nd ed. San Diego: Academic Press; 2002. p. 59–81.CrossRefGoogle Scholar
  2. 2.
    Matsuo K, Otaki N. Bone cell interactions through Eph/ephrin: bone modeling, remodeling and associated diseases. Cell Adhes Migr. 2012;6(2):148–56.CrossRefGoogle Scholar
  3. 3.
    Russell RM, Suter PM. Vitamin and trace mineral deficiency and excess. In: Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson J, Loscalzo J, editors. Harrison’s principles of internal medicine chapter 74. New York, NY: McGraw-Hill; 2012. p. 18e.Google Scholar
  4. 4.
    •• Kennedy M. The vitamin epidemic: what is the evidence for harm or value? Intern Med J. 2018;48(8):901–7 This review summarizes the physiological roles of Vitamins on body health. PubMedCrossRefGoogle Scholar
  5. 5.
    •• Anderson PH. Vitamin D activity and metabolism in bone. Curr Osteoporos Rep. 2017;15(5):443–9 This review summarizes the effect of Vitamin D on bone metabolism. PubMedCrossRefGoogle Scholar
  6. 6.
    •• Henning P, Conaway HH, Lerner UH. Retinoid receptors in bone and their role in bone remodeling. Front Endocrinol (Lausanne). 2015;11(6):31 This review summarizes the effect of Vitamin A on bone metabolism. Google Scholar
  7. 7.
    •• Akbari S, Rasouli-Ghahroudi AA. Vitamin K and bone metabolism: a review of the latest evidence in preclinical studies. Biomed Res Int. 2018;7(2018):4629383 This review summarizes the effect of Vitamin K on bone metabolism. Google Scholar
  8. 8.
    •• Kanchi MM, Shanmugam MK, Rane G, Sethi G, Kumar AP. Tocotrienols: the unsaturated sidekick shifting new paradigms in vitamin E therapeutics. Drug Discov Today. 2017;22(12):1765–81 This review summarizes the effect of Vitamin E on bone metabolism. PubMedCrossRefGoogle Scholar
  9. 9.
    • Aghajanian P, Hall S, Wongworawat MD, Mohan S. The roles and mechanisms of actions of vitamin C in bone: new developments. J Bone Miner Res. 2015;30(11):1945–55 This review summarizes the effect of Vitamin C on bone metabolism. PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    • Fratoni V, Brandi ML. B vitamins, homocysteine and bone health. Nutrients. 2015;7(4):2176–92 This review summarizes the effect of Vitamin B complex on bone metabolism. PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    Stein SH, Tipton DA. Vitamin D and its impact on oral health—an update. J Tenn Dent Assoc. 2011;91:30–3; quiz 34–35. PubMedGoogle Scholar
  12. 12.
    Bikle DD. Vitamin D and immune function: understanding common pathways. Curr Osteoporos Rep. 2009;7(2):58–63.CrossRefGoogle Scholar
  13. 13.
    Tang BM, Eslick GD, Nowson C, Smith C, Bensoussan A. Use of calcium or calcium in combination with vitamin D supplementation to prevent fractures and bone loss in people aged 50 years and older: a meta-analysis. Lancet. 2007;370(9588):657–66.PubMedCrossRefGoogle Scholar
  14. 14.
    Richy F, Schacht E, Bruyere O, Ethgen O, Gourlay M, Reginster JY. Vitamin D analogs versus native vitamin D in preventing bone loss and osteoporosis-related fractures: a comparative meta-analysis. Calcif Tissue Int. 2005;76(3):176–86.PubMedCrossRefGoogle Scholar
  15. 15.
    Richy F, Dukas L, Schacht E. Differential effects of D-hormone analogs and native vitamin D on the risk of falls: a comparative meta-analysis. Calcif Tissue Int. 2008;82(2):102–7.PubMedCrossRefGoogle Scholar
  16. 16.
    Morimoto S, Imanaka S, Koh E, Shiraishi T, Nabata T, Kitano S, et al. Comparison of the inhibitions of proliferation of normal and psoriatic fibroblasts by 1□,25-dihydroxyvitamin D3 and synthetic analogues of vitamin D3 with an oxygen atom in their side chain. Biochem Int. 1989;19(5):1143–9.PubMedGoogle Scholar
  17. 17.
    Uchiyama Y, Higuch IY, Takeda S, Masaki T, Shira-Ishi A, Sato K, et al. ED-71, a vitamin D analog, is a more potent inhibitor of bone resorption than alfacalcidol in an estrogen-deficient rat model of osteoporosis. Bone. 2002;30(4):582–8.PubMedCrossRefGoogle Scholar
  18. 18.
    Yoshizawa T, Handa Y, Uematsu Y, Takeda S, Sekine K, Yoshihara Y, et al. Mice lacking the vitamin D receptor exhibit impaired bone formation, uterine hypoplasia and growth retardation after weaning. Nat Genet. 1997;16(4):391–6.PubMedPubMedCentralCrossRefGoogle Scholar
  19. 19.
    Dardenne O, Prud'homme J, Arabian A, Glorieux FH, St-Arnaud R. Targeted inactivation of the 25-hydroxyvitamin D3-1□-hydroxylase gene (CYP27B1) creates an animal model of pseudovitamin D-deficiency rickets. Endocrinology. 2001;142(7):3135–41.PubMedCrossRefGoogle Scholar
  20. 20.
    Li YC, Amling M, Pirro AE, Priemel M, Meuse J, Baron R, et al. Normalization of mineral ion homeostasis by dietary means prevents hyperparathyroidism, rickets, and osteomalacia, but not alopecia in vitamin D receptor-ablated mice. Endocrinology. 1998;139(10):4391–6.PubMedCrossRefGoogle Scholar
  21. 21.
    Panda DK, Miao D, Bolivar I, Li J, Huo R, Hendy GN, et al. Inactivation of the 25-hydroxyvitamin D 1alpha-hydroxylase and vitamin D receptor demonstrates independent and interdependent effects of calcium and vitamin D on skeletal and mineral homeostasis. J Biol Chem. 2004;279(16):16754–66.PubMedCrossRefGoogle Scholar
  22. 22.
    Yamamoto Y, Yoshizawa T, Fukuda T, Shirode-Fukuda Y, Yu T, Sekine K, et al. Vitamin D receptor in osteoblasts is a negative regulator of bone mass control. Endocrinology. 2013;154(3):1008–20.PubMedCrossRefGoogle Scholar
  23. 23.
    •• Nakamichi Y, Udagawa N, Horibe K, Mizoguchi T, Yamamoto Y, Nakamura T, et al. VDR in osteoblast-lineage cells primarily mediates vitamin D treatment-induced increase in bone mass by suppressing bone resorption. J Bone Miner Res. 2017;32(6):1297–308 This literature shows the role of VDR in osteoblasts on bone metabolism. PubMedCrossRefGoogle Scholar
  24. 24.
    Lieben L, Masuyama R, Torrekens S, Van Looveren R, Schrooten J, Baatsen P, et al. Normocalcemia is maintained in mice under conditions of calcium malabsorption by vitamin D-induced inhibition of bone mineralization. J Clin Invest. 2012;122(5):1803–15.PubMedPubMedCentralCrossRefGoogle Scholar
  25. 25.
    Woeckel VJ, Alves RD, Swagemakers SM, Eijken M, Chiba H, van der Eerden BC, et al. 1 Alpha,25-(OH)2D3 acts in the early phase of osteoblast differentiation to enhance mineralization via accelerated production of mature matrix vesicles. J Cell Physiol. 2012;227(6):2668–76.PubMedCrossRefGoogle Scholar
  26. 26.
    Woeckel VJ, van der Eerden BC, Schreuders-Koedam M, Eijken M, Van Leeuwen JP. 1α,25-Dihydroxyvitamin D3 stimulates activin A production to fine-tune osteoblast-induced mineralization. J Cell Physiol. 2013;228(11):2167–74.PubMedCrossRefGoogle Scholar
  27. 27.
    Wang Y, Zhu J, DeLuca HF. Identification of the vitamin D receptor in osteoblasts and chondrocytes but not osteoclasts in mouse bone. J Bone Miner Res. 2014;29(3):685–92.PubMedCrossRefGoogle Scholar
  28. 28.
    Takeda S, Yoshizawa T, Nagai Y, Yamato H, Fukumoto S, Sekine K, et al. Stimulation of osteoclast formation by 1,25-dihydroxyvitamin D requires its binding to vitamin D receptor (VDR) in osteoblastic cells: studies using VDR knockout mice. Endocrinology. 1999;140(2):1005–8.PubMedCrossRefGoogle Scholar
  29. 29.
    D'Ambrosio DN, Clugston RD, Blaner WS. Vitamin A metabolism: an update. Nutrients. 2011;3(1):63–103.PubMedPubMedCentralCrossRefGoogle Scholar
  30. 30.
    Sommer A, West KP Jr. 1996 vitamin A deficiency: health, survival, and vision. New York, NY: Oxford University Press; 1996.Google Scholar
  31. 31.
    Okano J, Suzuki S, Shiota K. Involvement of apoptotic cell death and cell cycle perturbation in retinoic acid-induced cleft palate in mice. Toxicol Appl Pharmacol. 2007;221(1):42–56.PubMedCrossRefGoogle Scholar
  32. 32.
    Michaelsson K, Lithell H, Vessby B, Melhus H. Serum retinol levels and the risk of fracture. N Engl J Med. 2003;348(4):287–94.PubMedCrossRefGoogle Scholar
  33. 33.
    Promislow JH, Goodman-Gruen D, Slymen DJ, Barrett-Connor E. Retinol intake and bone mineral density in the elderly: the Rancho Bernardo Study. J Bone Miner Res. 2002;17(8):1349–58.PubMedCrossRefGoogle Scholar
  34. 34.
    Barker ME, McCloskey E, Saha S, Gossiel F, Charlesworth D, Powers HJ, et al. Serum retinoids and -carotene as predictors of hip and other fractures in elderly women. J Bone Miner Res. 2005;20(6):913–20.PubMedCrossRefGoogle Scholar
  35. 35.
    Maggio D, Barabani M, Pierandrei M, Polidori MC, Catani M, Mecocci P, et al. Marked decrease in plasma antioxidants in aged osteoporotic women: results of a cross-sectional study. J Clin Endocrinol Metab. 2003;88:1523–7.PubMedCrossRefGoogle Scholar
  36. 36.
    Kawahara TN, Krueger DC, Engelke JA, Harke JM, Binkley NC. Short-term vitamin A supplementation does not affect bone turnover in men. J Nutr. 2002;132(6):1169–72.PubMedCrossRefGoogle Scholar
  37. 37.
    Rejnmark L, Vestergaard P, Charles P, Hermann AP, Brot C, Eiken P, et al. No effect of vitamin A intake on bone mineral density and fracture risk in perimenopausal women. Osteoporos Int. 2004;15(11):872–54.PubMedCrossRefGoogle Scholar
  38. 38.
    Raisz LG. Bone resorption in tissue culture. Factors influencing the response to parathyroid hormone. J Clin Invest. 1965;44:103–16.PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Conaway HH, Persson E, Halén M, Granholm S, Svensson O, Pettersson U, et al. Retinoids inhibit differentiation of hematopoietic osteoclast progenitors. FASEB J. 2009;23(10):3526–38.PubMedCrossRefGoogle Scholar
  40. 40.
    Saneshige S, Mano H, Tezuka K, Kakudo S, Mori Y, Honda Y, et al. Retinoic acid directly stimulates osteoclastic bone resorption and gene expression of cathepsin K/OC-2. Biochem J. 1995;309(3):721–4.PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    Lind T, Lind PM, Jacobson A, Hu L, Sundqvist A, Risteli J, et al. High dietary intake of retinol leads to bone marrow hypoxia and diaphyseal endosteal mineralization in rats. Bone. 2011;48(3):496–506.PubMedCrossRefGoogle Scholar
  42. 42.
    Shearer MJ, Fu X, Booth SL. Vitamin K nutrition, metabolism, and requirements: current concepts and future research. Adv Nutr. 2012;3(2):182–95.PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Myneni VD, Mezey E. Regulation of bone remodeling by vitamin K2. Oral Dis. 2018;24(1–2):67–71.PubMedPubMedCentralCrossRefGoogle Scholar
  44. 44.
    Nagura N, Komatsu J, Iwase H, Hosoda H, Ohbayashi O, Nagaoka I, et al. Effects of the combination of vitamin K and teriparatide on the bone metabolism in ovariectomized rats. Biomed Rep. 2015;3(3):295–300.PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    Iwasaki-Ishizuka Y, Yamato H, Murayama H, Ezawa I, Kurokawa K, Fukagawa M. Menatetrenone rescues bone loss by improving osteoblast dysfunction in rats immobilized by sciatic neurectomy. Life Sci. 2005;76(15):1721–34.PubMedCrossRefGoogle Scholar
  46. 46.
    Hauschka PV, Lian JB, Cole DE, Gundberg CM. Osteocalcin and matrix Gla protein: vitamin K-dependent proteins in bone. Physiol Rev. 1989;69(3):990–1047.PubMedCrossRefGoogle Scholar
  47. 47.
    Ducy P, Desbois C, Boyce B, Pinero G, Story B, Dunstan C, et al. Increased bone formation in osteocalcin-deficient mice. Nature. 1996;382(6590):448–52.CrossRefGoogle Scholar
  48. 48.
    Gundberg CM, Nieman SD, Abrams S, Rosen H. Vitamin K status and bone health: an analysis of methods for determination of undercarboxylated osteocalcin. J Clin Endocrinol Metab. 1998;83(9):3258–66.PubMedGoogle Scholar
  49. 49.
    •• Fiordellisi W, White K, Schweizer M. A Systematic Review and meta-analysis of the association between vitamin K antagonist use and fracture. J Gen Intern Med. 2019;34:304–11 This review summarizes the effect of Vitamin K antagonist on bone metabolism. PubMedCrossRefGoogle Scholar
  50. 50.
    Hamidi MS, Cheung AM. Vitamin K and musculoskeletal health in postmenopausal women. Mol Nutr Food Res. 2014;58(8):1647–57.PubMedCrossRefGoogle Scholar
  51. 51.
    Kim M, Na W, Sohn C. Vitamin K1 (phylloquinone) and K2 (menaquinone-4) supplementation improves bone formation in a high-fat diet-induced obese mice. J Clin Biochem Nutr. 2013;53(2):108–13.PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    Poon CC, Li RW, Seto SW, Kong SK, Ho HP, Hoi MP, et al. In vitro vitamin K2 and 1α,25-dihydroxyvitamin D3 combination enhances osteoblasts anabolism of diabetic mice. Eur J Pharmacol. 2015;15(767):30–40.CrossRefGoogle Scholar
  53. 53.
    Koshihara Y, Hoshi K, Okawara R, Ishibashi H, Yamamoto S. Vitamin K stimulates osteoblastogenesis and inhibits osteoclastogenesis in human bone marrow cell culture. J Endocrinol. 2003;176(3):339–48.PubMedCrossRefGoogle Scholar
  54. 54.
    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(25):16927–34.PubMedCrossRefGoogle Scholar
  55. 55.
    Katsuyama H, Saijoh K, Otsuki T, Tomita M, Fukunaga M, Sunami S. Menaquinone-7 regulates gene expression in osteoblastic MC3T3E1 cells. Int J Mol Med. 2007;19(2):279–84.PubMedGoogle Scholar
  56. 56.
    Akiyama Y, Hara K, Tajima T, Murota S, Morita I. Effect of vitamin K2 (menatetrenone) on osteoclast-like cell formation in mouse bone marrow cultures. Eur J Pharmacol. 1994;263(1–2):181–5.PubMedCrossRefGoogle Scholar
  57. 57.
    Kameda T, Miyazawa K, Mori Y, Yuasa T, Shiokawa M, Nakamaru Y, et al. Vitamin K2 inhibits osteoclastic bone resorption by inducing osteoclast apoptosis. Biochem Biophys Res Commun. 1996;220(3):515–9.PubMedCrossRefGoogle Scholar
  58. 58.
    •• Peh HY, Tan WS, Liao W, Wong WS. Vitamin E therapy beyond cancer: tocopherol versus tocotrienol. Pharmacol Ther. 2016;162:152–69 This review summarizes the physiological roles of vitamin E on body health. PubMedCrossRefGoogle Scholar
  59. 59.
    Basu S, Michaëlsson K, Olofsson H, Johansson S, Melhus H. Association between oxidative stress and bone mineral density. Biochem Biophys Res Commun. 2001;288(1):275–9.PubMedCrossRefGoogle Scholar
  60. 60.
    Pasco J, Henry M, Wilkinson L, Nicholson G, Schneider H, Kotowicz M. Antioxidant vitamin supplements and markers of bone turnover in a community sample of nonsmoking women. J Women's Health (Larchmt). 2006;15:295–300.CrossRefGoogle Scholar
  61. 61.
    Yang TC, Duthie GG, Aucott LS, Macdonald HM. Vitamin E homologues α- and γ-tocopherol are not associated with bone turnover markers or bone mineral density in peri-menopausal and post-menopausal women. Osteoporos Int. 2016;27(7):2281–90.PubMedCrossRefGoogle Scholar
  62. 62.
    Ibrahim N', Mohamed N, Soelaiman IN, Shuid AN. The effects of targeted deliveries of lovastatin and tocotrienol on ossification-related gene expressions in fracture healing in an osteoporosis rat model. Int J Environ Res Public Health 2015;12: 12958–12976.CrossRefGoogle Scholar
  63. 63.
    Ibrahim N', Khamis MF, Mod Yunoh MF, Abdullah S, Mohamed N, Shuid AN. Targeted delivery of lovastatin and tocotrienol to fracture site promotes fracture healing in osteoporosis model: micro-computed tomography and biomechanical evaluation. PLoS One 2014;9: e115595.CrossRefGoogle Scholar
  64. 64.
    Chin KY, Ima-Nirwana S. Effects of annatto-derived tocotrienol supplementation on osteoporosis induced by testosterone deficiency in rats. Clin Interv Aging. 2014;9:1247–59.PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Maniam S, Mohamed N, Shuid AN, Soelaiman IN. Palm tocotrienol exerted better antioxidant activities in bone than alpha-tocopherol. Basic Clin Pharmacol Toxicol. 2008;103(1):55–60.PubMedCrossRefGoogle Scholar
  66. 66.
    Abd Manan N, Mohamed N, Shuid AN. Effects of low-dose versus high-dose γ-tocotrienol on the bone cells exposed to the hydrogen peroxide-induced oxidative stress and apoptosis. Evid Based Complement Alternat Med. 2012;2012:680834.PubMedPubMedCentralCrossRefGoogle Scholar
  67. 67.
    Fujita K, Iwasaki M, Ochi H, Fukuda T, Ma C, Miyamoto T, et al. Vitamin E decreases bone mass by stimulating osteoclast fusion. Nat Med. 2012;18(4):589–94.PubMedCrossRefGoogle Scholar
  68. 68.
    Marini JC, Cabral WA, Barnes AM, Chang W. Components of the collagen prolyl 3-hydroxylation complex are crucial for normal bone development. Cell Cycle. 2007;6(14):1675–81.PubMedCrossRefGoogle Scholar
  69. 69.
    Prynne CJ, Mishra GD, O'Connell MA, Muniz G, Laskey MA, Yan L, et al. Fruit and vegetable intakes and bone mineral status: a cross sectional study in 5 age and sex cohorts. Am J Clin Nutr. 2006;83(6):1420–8.PubMedCrossRefGoogle Scholar
  70. 70.
    Sahni S, Hannan MT, Blumberg J, Cupples LA, Kiel DP, Tucker KL. Protective effect of total and supplemental vitamin C intake on the risk of hip fracture-a 17-year follow-up from the Framingham Osteoporosis Study. Osteoporos Int. 2009;20(11):1853–61.PubMedPubMedCentralCrossRefGoogle Scholar
  71. 71.
    Liu ZM, Leung J, Wong SY, Wong CK, Chan R, Woo J. Greater fruit intake was associated with better bone mineral status among Chinese elderly men and women: results of Hong Kong Mr. Os and Ms. Os studies. J Am Med Dir Assoc. 2015;16(4):309–15.PubMedCrossRefGoogle Scholar
  72. 72.
    Kim YA, Kim KM, Lim S, Choi SH, Moon JH, Kim JH, et al. Favorable effect of dietary vitamin C on bone mineral density in postmenopausal women (KNHANES IV, 2009): discrepancies regarding skeletal sites, age, and vitamin D status. Osteoporos Int. 2015;26(9):2329–37.PubMedCrossRefGoogle Scholar
  73. 73.
    Maeda N, Hagihara H, Nakata Y, Hiller S, Wilder J, Reddick R. Aortic wall damage in mice unable to synthesize ascorbic acid. Proc Natl Acad Sci U S A. 2000;97(2):841–6.PubMedPubMedCentralCrossRefGoogle Scholar
  74. 74.
    Mohan S, Kapoor A, Singgih A, Zhang Z, Taylor T, Yu H, et al. Spontaneous fractures in the mouse mutant sfx are caused by deletion of the gulonolactone oxidase gene, causing vitamin C deficiency. J Bone Miner Res. 2005;20(9):1597–610.PubMedCrossRefGoogle Scholar
  75. 75.
    Gabbay KH, Bohren KM, Morello R, Bertin T, Liu J. Vogel PAscorbate synthesis pathway: dual role of ascorbate in bone homeostasis. J Biol Chem. 2010;285(25):19510–20.PubMedPubMedCentralCrossRefGoogle Scholar
  76. 76.
    Franceschi RT, Iyer BS. Relationship between collagen synthesis and expression of the osteoblast phenotype in MC3T3-E1 cells. J Bone Miner Res. 1992;7(2):235–46.PubMedPubMedCentralCrossRefGoogle Scholar
  77. 77.
    Park JK, Lee EM, Kim AY, Lee EJ, Min CW, Kang KK, et al. Vitamin C deficiency accelerates bone loss inducing an increase in PPAR-γ expression in SMP30 knockout mice. Int J Exp Pathol. 2012;93(5):332–40.PubMedPubMedCentralCrossRefGoogle Scholar
  78. 78.
    Zunich SM, Valdovinos M, Douglas T, Walterhouse D, Iannaccone P, Lamm ML. Osteoblast-secreted collagen upregulates paracrine Sonic hedgehog signaling by prostate cancer cells and enhances osteoblast differentiation. Mol Cancer. 2012;11:30.PubMedPubMedCentralCrossRefGoogle Scholar
  79. 79.
    Blaschke K, Ebata KT, Karimi MM, Zepeda-Martínez JA, Goyal P, Mahapatra S, et al. Vitamin C induces Tet-dependent DNA demethylation and a blastocyst-like state in ES cells. Nature. 2013;500(7461):222–6.PubMedPubMedCentralCrossRefGoogle Scholar
  80. 80.
    Le Nihouannen D, Barralet JE, Fong JE, Komarova SV. Ascorbic acid accelerates osteoclast formation and death. Bone. 2010;46(5):1336–43.PubMedCrossRefGoogle Scholar
  81. 81.
    Otsuka E, Kato Y, Hirose S, Hagiwara H. Role of ascorbic acid in the osteoclast formation: induction of osteoclast differentiation factor with formation of the extracellular collagen matrix. Endocrinology. 2000;141(8):3006–11.PubMedCrossRefGoogle Scholar
  82. 82.
    van Wijngaarden JP, Doets EL, Szczecińska A, Souverein OW, Duffy ME, Dullemeijer C, et al. Vitamin B12, folate, homocysteine, and bone health in adults and elderly people: a systematicreview with meta-analyses. J Nutr Metab. 2013;2013:486186.PubMedPubMedCentralGoogle Scholar
  83. 83.
    Roman-Garcia P, Quiros-Gonzalez I, Mottram L, Lieben L, Sharan K, Wangwiwatsin A, et al. Vitamin B12-dependent taurine synthesis regulates growth and bone mass. J Clin Invest. 2014;124(7):2988–3002.PubMedPubMedCentralCrossRefGoogle Scholar
  84. 84.
    Bailey RL, van Wijngaarden JP. The role of B-vitamins in bone health and disease in older adults. Curr Osteoporos Rep. 2015;13(4):256–61.PubMedCrossRefGoogle Scholar
  85. 85.
    Dai Z, Wang R, Ang LW, Yuan JM, Koh WP. Bone turnover biomarkers and risk of osteoporotic hip fracture in an Asian population. Bone. 2016;83:171–7.PubMedCrossRefGoogle Scholar
  86. 86.
    Sawka AM, Ray JG, Yi Q, Josse RG, Lonn E. Randomized clinical trial of homocysteine level lowering therapy and fractures. Arch Intern Med. 2007;167(19):2136–9.PubMedCrossRefGoogle Scholar
  87. 87.
    Gommans J, Yi Q, Eikelboom JW, Hankey GJ, Chen C, Rodgers H. VITATOPS trial study group. The effect of homocysteine-lowering with B-vitamins on osteoporotic fractures in patients with cerebrovascular disease: substudy of VITATOPS, a randomised placebo-controlled trial. BMC Geriatr. 2013;13:88.PubMedPubMedCentralCrossRefGoogle Scholar
  88. 88.
    Stone KL, Lui LY, Christen WG, Troen AM, Bauer DC, Kado D, et al. Effect of combination folic acid, vitamin B6 , and vitamin B12 supplementation on fracture risk in women: a randomized, controlled trial. J Bone Miner Res. 2017;32(12):2331–8.PubMedPubMedCentralCrossRefGoogle Scholar
  89. 89.
    Vaes BL, Lute C, Blom HJ, Bravenboer N, de Vries TJ, Everts V, et al. Vitamin B12 deficiency stimulates osteoclastogenesis via increased homocysteine and methylmalonic acid. Calcif Tissue Int. 2009;84(5):413–22.PubMedCrossRefGoogle Scholar

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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Oral Health/Brain Health/Total Health Research Center, Laboratory of Molecular and Cellular Biochemistry, Faculty of Dental ScienceKyushu UniversityFukuokaJapan

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