Open Access Open Access  Restricted Access Subscription Access

Vitamin B12 as a Regulator of Bone Health


Affiliations
1 Metabolic Research Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110 067, India
 

In the early 1920s, the anti-anaemic effect of liver-rich diet had been recognized. The anti-anaemic substance from the liver was isolated by 1950 and called ‘vitamin B12’ (hereafter B12). It took another 20 years to structurally define and chemically synthesize B12 in its pure form. Since then, it has been recognized that B12 modulates a variety of biological systems, from immune system to bone homeostasis. Recent clinical studies have shown that B12 deficiency is likely to be an important etiological factor in the pathogenesis of bone degeneration. In this regard, either observational studies that aimed to verify an association between low B12 level and bone mass, or clinical trials on the effect of B12 as a supplementary treatment in low bone mass patients have been presented in the emerging clinical literature. Recently, we created a mouse genetic model of B12 deficiency to elucidate its mode of action by genetic deletion of gastric intrinsic factor, a protein essential for the absorption of B12 from the gut. This has led to the identification of a novel gut–liver-bone axis that has the potential to be pharmacologically targeted for treating low bone mass diseases in humans. In this review, we revisit the history of B12 from its discovery in the early 20th century to the elucidation of its mode of action in the bone till date.

Keywords

Bone Formation, Endocrinology, Osteoblasts, Vitamin B12.
User
Notifications
Font Size

  • Karsenty, G., The genetic transformation of bone biology. Genes Develop., 1999, 13, 3037–3051.
  • Khosla, S. and Riggs, B. L., Pathophysiology of age-related bone loss and osteoporosis. Endocrinol. Metab. Clin. North Am., 2005, 34, 1015–1030.
  • Ducy, P. and Karsenty, G., The two faces of serotonin in bone biology. J. Cell Biol., 2010, 191, 7–13.
  • Moser, U. and Elmadfa, I., 100 years of vitamins. Int. J. Vitam. Nutr. Res., 2012, 82, 309.
  • Bonjour, J. P. et al., Minerals and vitamins in bone health: the potential value of dietary enhancement. Br. J. Nutr., 2009, 101, 1581–1596.
  • Roman-Garcia, P. et al., Vitamin B12-dependent taurine synthesis regulates growth and bone mass. J. Clin. Invest., 2014, 124, 2988–3002.
  • West, R., Activity of Vitamin B12 in Addisonian pernicious anemia. Science, 1948, 107, 398.
  • Minot, G. R. and Murphy, W. P., Landmark article (JAMA 1926). Treatment of pernicious anaemia by a special diet. JAMA, 1983, 250, 3328–3335.
  • Robscheit-Robbins, F. S. and Whipple, G. H., Blood regeneration in severe anemia: Xiv. A liver fraction potent in pernicious anemia fed alone and combined with whole liver, liver ash and fresh bile. J. Exp. Med., 1929, 49, 215–227.
  • Minot, G. R. and Murphy, W. P., Treatment of pernicious anaemia by a special diet. Yale J. Biol. Med., 2001, 74, 341–353.
  • Cohn, E. J., et al., The state in nature of the active principle in pernicious anaemia of catalase, and of other components of liver. Science, 1949, 109, 443.
  • Rickes, E. L. et al., Crystalline vitamin B12. Science, 1948, 107, 396–397.
  • Hodgkin, D. C. et al., Structure of vitamin B12. Nature, 1956, 178, 64–66.
  • Eschenmoser, A. and Wintner, C. E., Natural product synthesis and vitamin B12. Science, 1977, 196, 1410–1420.
  • Woodward, R. B., The total synthesis of vitamin B12. Pure Appl. Chem., 1973, 33, 145–177.
  • Roth, J. R., Lawrence, J. G. and Bobik, T. A., Cobalamin (coenzyme B12): synthesis and biological significance. Annu. Rev. Microbiol., 1996, 50, 137–181.
  • Nielsen, M. J. et al., Vitamin B12 transport from food to the body’s cells – a sophisticated, multistep pathway. Nature Rev., Gastroenterol. Hepatol., 2012, 9, 345–354.
  • Schilling, R. F., Pernicious anaemia and other forms of vitamin B12 deficiency. Wisconsin Med. J., 1969, 68, 244.
  • Matthews, R. G., A love affair with vitamins. J. Biol. Chem., 2009, 284, 26217–26228.
  • Carlmark, B. and Reizenstein, P., Comparison of methods to diagnose deficiency or malabsorption of vitamin B12. Scand. J. Gastroenterol., 1974, S29, 39–42.
  • Graber, S. E., Scheffel, U., Hodkinson, B. and McIntyre, P. A., Placental transport of vitamin B12 in the pregnant rat. J. Clin. Invest., 1971, 50, 1000–1004.
  • Higginbottom, M. C., Sweetman, L. and Nyhan, W. L., A syndrome of methylmalonic aciduria, homocystinuria, megaloblastic anaemia and neurologic abnormalities in a vitamin B12 deficient breast-fed infant of a strict vegetarian. N. Engl. J. Med., 1978, 299(7), 317–323.
  • Kalhan, S. C., One-carbon metabolism, fetal growth and long-term consequences. Nestle Nutr. Inst. Workshop Ser., 2013, 74, 127–138.
  • Goerss, J. B. et al., Risk of fractures in patients with pernicious anaemia. J. Bone Miner. Res., 1992, 7, 573–579.
  • Dhonukshe-Rutten, R. A. et al., Low bone mineral density and bone mineral content are associated with low cobalamin status in adolescents. Eur. J. Nutr., 2005, 44, 341–347.
  • Muthayya, S. et al., Low maternal vitamin B12 status is associated with intrauterine growth retardation in urban South Indians. Eur. J. Clin. Nutr., 2006, 60, 791–801.
  • Tucker, K. L. et al., Low plasma vitamin B12 is associated with lower BMD: the Framingham Osteoporosis Study. J. Bone Miner. Res., 2005, 20, 152–158.
  • Carmel, R. et al., Cobalamin and osteoblast-specific proteins. New Engl. J. Med., 1988, 319, 70–75.
  • Dhonukshe-Rutten, R. A., Homocysteine and vitamin B12 status relate to bone turnover markers, broadband ultrasound attenuation, and fractures in healthy elderly people. J. Bone Miner. Res., 2005, 20(6), 921–929.
  • Cagnacci, A. et al., Relation of folates, vitamin B12 and homocysteine to vertebral bone mineral density change in postmenopausal women. A 5-year longitudinal evaluation. Bone, 2008, 42(2), 314–320.
  • Morris, M. S., Jacques, P. F. and Selhub, J., Relation between homocysteine and B-vitamin status indicators and bone mineral density in older Americans. Bone, 2005, 37(2), 234–242.
  • Rejnmark, L. et al., Dietary intake of folate, but not vitamin B2 or B12, is associated with increased bone mineral density 5 years after the menopause: results from a 10-year follow up study in early postmenopausal women. Calcif. Tissue Int., 2008, 82(1), 1–11.
  • Herrmann, W. et al., One year B and D vitamins supplementation improves metabolic bone markers. Clin. Chem. Lab. Med., 2013, 51(3), 639–647.
  • Sato, Y. et al., Effect of folate and mecobalamin on hip fractures in patients with stroke: a randomized controlled trial. JAMA, 2005, 293(9), 1082–1088.
  • Herrmann, M. et al., Experimental folate and vitamin B12 deficiency does not alter bone quality in rats. J. Bone Miner. Res., 2009, 24(4), 589–596.
  • Holstein, J. H. et al., Deficiencies of folate and vitamin B12 do not affect fracture healing in mice. Bone, 2010, 47(1), 151–155.
  • Bex, M. and Bouillon, R., Growth hormone and bone health. Horm. Res., 2003, 60(3), 80–86.
  • Clemens, T. L., Vitamin B12 deficiency and bone health. New Engl. J. Med., 2014, 371, 963–964.

Abstract Views: 262

PDF Views: 68




  • Vitamin B12 as a Regulator of Bone Health

Abstract Views: 262  |  PDF Views: 68

Authors

Vijay K. Yadav
Metabolic Research Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110 067, India

Abstract


In the early 1920s, the anti-anaemic effect of liver-rich diet had been recognized. The anti-anaemic substance from the liver was isolated by 1950 and called ‘vitamin B12’ (hereafter B12). It took another 20 years to structurally define and chemically synthesize B12 in its pure form. Since then, it has been recognized that B12 modulates a variety of biological systems, from immune system to bone homeostasis. Recent clinical studies have shown that B12 deficiency is likely to be an important etiological factor in the pathogenesis of bone degeneration. In this regard, either observational studies that aimed to verify an association between low B12 level and bone mass, or clinical trials on the effect of B12 as a supplementary treatment in low bone mass patients have been presented in the emerging clinical literature. Recently, we created a mouse genetic model of B12 deficiency to elucidate its mode of action by genetic deletion of gastric intrinsic factor, a protein essential for the absorption of B12 from the gut. This has led to the identification of a novel gut–liver-bone axis that has the potential to be pharmacologically targeted for treating low bone mass diseases in humans. In this review, we revisit the history of B12 from its discovery in the early 20th century to the elucidation of its mode of action in the bone till date.

Keywords


Bone Formation, Endocrinology, Osteoblasts, Vitamin B12.

References





DOI: https://doi.org/10.18520/cs%2Fv114%2Fi08%2F1632-1638