B-vitamins and bone in health and disease: The current evidence

Proceedings of the Nutrition Society

Volumn 755, Issue , 2014, Pages

  Clarke, M ^a   Ward, M ^a   Strain, J J ^a   Hoey, L ^a   Dickey, W ^b   McNulty, H ^a  

^a UNIVERSITY OF ULSTER   (United Kingdom)

^b ALTNAGELVIN HOSPITAL   (United Kingdom)

Author keywords

B vitamins; Coeliac disease; Homocysteine; MTHFR 677C T polymorphism

Indexed keywords

5,10 METHYLENETETRAHYDROFOLATE REDUCTASE (FADH2); BIOLOGICAL MARKER; CYANOCOBALAMIN; FOLIC ACID; HOMOCYSTEINE; PYRIDOXINE; VITAMIN B GROUP;

AGING; AMINO ACID METABOLISM; BONE DENSITY; BONE DISEASE; CELIAC DISEASE; CONFERENCE PAPER; EVIDENCE BASED MEDICINE; GENETIC ASSOCIATION; GENETIC POLYMORPHISM; GENETIC SUSCEPTIBILITY; HIGH RISK PATIENT; HUMAN; METHYLENETETRAHYDROFOLATE REDUCTASE GENE; NUTRITION; OSTEOPOROSIS; RANDOMIZED CONTROLLED TRIAL (TOPIC); VITAMIN SUPPLEMENTATION;

EID: 84938094683     PISSN: 00296651     EISSN: 14752719     Source Type: Journal    
DOI: 10.1017/S0029665114000044     Document Type: Conference Paper

References (90)

1. Peck WA, Burckhardt P, Christiansen C et al. (1993) Consensus development conference - diagnosis, prophylaxis, and treatment of osteoporosis. Am J Med 94, 646-650.
2. Strom O, Borgstrom F, Kanis JA et al. (2011) Osteoporosis: burden, health care provision and opportunities in the EU: a report prepared in collaboration with the International Osteoporosis Foundation (IOF) and the European Federation of Pharmaceutical Industry Associations (EFPIA). Arch Osteoporos 6, 59-155.
3. Van Staa TP, Dennison EM, Leufkens HGM et al. (2001) Epidemiology of fractures in England and Wales. Bone 29, 517-522.
4. Prentice A. (2001) The relative contribution of diet and genotype to bone development. Proc Nutr Soc 60, 45-52.
5. Kanis JA, McCloskey EV, Johansson H et al. (2013) European guidance for the diagnosis and management of osteoporosis in postmenopausal women. Osteoporos Int 24, 23-57.
6. Kanis JA, Alexeeva L, Bonjour JP et al. (1994) Assessment of fracture risk and its application to screening for postmenopausal osteoporosis - synopsis of a who report. Osteoporos Int 4, 368-381.
7. Cummings SR, Browner W, Cummings SR et al. (1993) Bone density at various sites for prediction of hip fractures. Lancet 341, 72-75.
8. Marshall D, Johnell O & Wedel H (1996) Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures. BMJ 312, 1254-1259.
9. Kanis JA, McCloskey EV, Johansson H et al. (2010) Development and use of FRAXA (R) in osteoporosis. Osteoporos Int 21, 407-413.
10. Michaelsson K, Melhus H, Ferm H et al. (2005) Genetic liability to fractures in the elderly. Arch Intern Med 165, 1825-1830.
11. Tang BMP, Eslick GD, Nowson C et al. (2007) 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 370, 657-666.
12. 12, folate, homocysteine, and bone health in adults and elderly people: a systematic review with meta-analyses. J Nutr Metab 2013, 486186.
13. Wang H & Liu C (2012) Association of MTHFR C667T polymorphism with bone mineral density and fracture risk: an updated meta-analysis. Osteoporos Int 23, 2625-2634.
14. McKinley MC, McNulty H, McPartlin J et al. (2001) Low-dose vitamin B-6 effectively lowers fasting plasma homocysteine in healthy elderly persons who are folate and riboflavin replete. Am J Clin Nutr 73, 759-764.
15. Homocysteine Lowering Trialists' Collaboration (1998) Lowering blood homocysteine with folic acid based supplements: meta-analysis of randomised trials. BMJ 316, 894-898.
16. Schwahn B & Rozen R (2001) Polymorphisms in the methylenetetrahydrofolate reductase gene: clinical consequences. Am J Pharmacogenomics 1, 189-201.
17. Yamada K, Chen Z, Rozen R et al. (2001) Effects of common polymorphisms on the properties of recombinant human methylenetetrahydrofolate reductase. Proc Natl Acad Sci USA 98, 14853-14858.
18. Malinow M, Bostom A & Krauss R (1999) Homocyst(e) ine, diet, and cardiovascular diseases - a statement for healthcare professionals from the Nutrition Committee, American Heart Association. Circulation 99, 178-182.
19. Frosst P, Blom HJ, Milos R et al. (1995) A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet 10, 111-113.
20. Molloy A, Daly S, Mills J et al. (1997) Thermolabile variant of 5, 10-methylenetetrahydrofolate reductase associated with low red-cell folates: implications for folate intake recommendations. Lancet 349, 1591-1593.
21. McNulty H, Dowey le RC, Strain JJ et al. (2006) Riboflavin lowers homocysteine in individuals homozygous for the MTHFR 677C->T polymorphism. Circulation 113, 74-80.
22. Botto LD & Yang Q (2000) 5, 10-Methylenetetrahydrofolate reductase gene variants and congenital anomalies: a HuGE review. Am J Epidemiol 151, 862-877.
23. Wilcken B, Bamforth F, Li Z et al. (2003) Geographical and ethnic variation of the 677C>T allele of 5, 10 methylenetetrahydrofolate reductase (MTHFR): findings from over 7000 newborns from 16 areas world wide. J Med Genet 40, 619-625.
24. Refsum H, Smith A, Ueland P et al. (2004) Facts and recommendations about total homocysteine determinations: an expert opinion. Clin Chem 50, 3-32.
25. Mudd S, Skovby F, Levy H et al. (1985) The natural-history of homocystinuria due to cystathionine betasynthase deficiency. Am J Hum Genet 37, 1-31.
26. Maron BA & Loscalzo J (2009) The treatment of hyperhomocysteinemia. Annu Rev Med 60, 39-54.
27. Eastell R, Vieira N, Yergey A et al. (1992) Perniciousanemia as a risk factor for osteoporosis. Clin Sci 82, 681-685.
28. Goerss J, Kim C, Atkinson E et al. (1992) Risk of fractures in patients with pernicious-anemia. J Bone Miner Res 7, 573-579.
29. Dai Z, Wang R, Ang LW et al. (2013) Dietary B vitamin intake and risk of hip fracture: the Singapore Chinese Health Study. Osteoporos Int 24, 2049-2059.
30. Yang J, Hu X, Zhang Q et al. (2012) Homocysteine level and risk of fracture: a meta-analysis and systematic review. Bone 51, 376-382.
31. Enneman AW, Swart KM, van Wijngaarden JP et al. (2012) Association between plasma homocysteine and bone density and quality parameters in the elderly. Bone 50, S134-S134.
32. LeBoff MS (2009) Homocysteine levels and risk of hip fracture in postmenopausal women. J Clin Endocrinol Metab 94, 1207-1213.
33. Gjesdal C, Voliset S, Ueland P et al. (2007) Plasma homocysteine, folate, and vitamin B sub(12) and the risk of hip fracture: the Hordaland Homocysteine study. J Bone Miner Res 22, 747-756.
34. Yazdanpanah N, Zillikens MC, Rivadeneira F et al. (2007) Effect of dietary B vitamins on BMD and risk of fracture in elderly men and women: the Rotterdam study. Bone 41, 987-994.
35. Dhonukshe-Rutten R, Pluijm S, de Groot L et al. (2005) Homocysteine and vitamin B-12 status relate to bone turnover markers, broadband ultrasound attenuation, and fractures in healthy elderly people. J Bone Miner Res 20, 921-929.
36. van Meurs JBJ, Dhonukshe-Rutten RAM, Pluijm SMF et al. (2004) Homocysteine levels and the risk of osteoporotic fracture. N Engl J Med 350, 2033-2041.
37. McLean RR, Jacques PF, Selhub J et al. (2004) Homocysteine as a predictive factor for hip fracture in older persons. N Engl J Med 350, 2042-2049.
38. Kim B, Koh J, Ahn SH et al. (2013) High serum total homocysteine levels accelerate hip bone loss in healthy premenopausal women and men. Bone 52, 56-62.
39. Zhu K, Beilby J, Dick IM et al. (2009) The effects of homocysteine and MTHFR genotype on hip bone loss and fracture risk in elderly women. Osteoporos Int 20, 1183-1191.
40. Gjesdal CG, Vollset SE, Ueland PM et al. (2006) Plasma total homocysteine level and bone mineral density - the Hordaland homocysteine study. Arch Intern Med 166, 88-94.
41. McLean RR, Jacques PF, Selhub J et al. (2008) Plasma B Vitamins, Homocysteine, and their relation with bone loss and hip fracture in elderly men and women. J Clin Endocrinol Metab 93, 2206-2212.
42. Morris M, Jacques P & Selhub J (2005) Relation between homocysteine and B-vitamin status indicators and bone mineral density in older Americans. Bone 37, 234-242.
43. 12 is associated with lower BMD: the Framingham Osteoporosis study. J Bone Miner Res 20, 152-158.
44. 12 to bone mineral density of postmenopausal women. Bone 33, 956-959.
45. Rumbak I, Zizic V, Sokolic L et al. (2012) Bone mineral density is not associated with homocysteine level, folate and vitamin B-12 status. Arch Gynecol Obstet 285, 991-1000.
46. (12) deficiencies in osteoporosis: a systematic review. Clin Chem Lab Med : CCLM/FESCC 45, 1621-1632.
47. Yazdanpanah N, Uitterlinden AG, Zillikens MC et al. (2008) Low dietary riboflavin but not folate predicts increased fracture risk in postmenopausal women homozygous for the MTHFR 677 T allele. J Bone Miner Res 23, 86-94.
48. Hong X, Hsu Y, Terwedow H et al. (2007) Association of the methylenetetrahydrofolate reductase C677T polymorphism and fracture risk in Chinese postmenopausal women. Bone 40, 737-742.
49. Abrahamsen B, Madsen JS, Tofteng CL et al. (2005) Are effects of MTHFR (C677T) genotype on BMD confined to women with low folate and riboflavin intake? Analysis of food records from the Danish osteoporosis prevention study. Bone 36, 577-583.
50. Macdonald HM, McGuigan FE, Fraser WD et al. (2004) Methylenetetrahydrofolate reductase polymorphism interacts with riboflavin intake to influence bone mineral density. Bone 35, 957-964.
51. McLean RR, Karasik D, Selhub J et al. (2004) Association of a common polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene with bone phenotypes depends on plasma folate status. J Bone Miner Res 19, 410-418.
52. Abrahamsen B, Madsen JS, Tofteng CL et al. (2003) A common methylenetetrahydrofolate reductase (C677T) polymorphism is associated with low bone mineral density and increased fracture incidence after menopause: longitudinal data from the Danish osteoporosis prevention study. J Bone Miner Res 18, 723-729.
53. Miyao M, Morita H, Hosoi T et al. (2000) Association of methylenetetrahydrofolate reductase (MTHFR) polymorphism with bone mineral density in postmenopausal Japanese women. Calcif Tissue Int 66, 190-194.
54. Sato Y, Honda Y, Iwamoto J et al. (2005) Effect of folate and mecobalamin on hip fractures in patients with stroke: a randomized controlled trial. JAMA 293, 1082-1088.
55. Gommans J, Yi Q, Eikelboom JW et al. (2013) 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 13, 88.
56. Sawka AM, Ray JG, Yi Q et al. (2007) Randomized clinical trial of homocysteine level lowering therapy and fractures. Arch Int Med 167, 2136-2139.
57. Herrmann M, Tami A, Wildemann B et al. (2009) Hyperhomocysteinemia induces a tissue specific accumulation of homocysteine in bone by collagen binding and adversely affects bone. Bone 44, 467-475.
58. Lubec B, Fang-Kircher S, Lubec T et al. (1996) Evidence for McKusick's hypothesis of deficient collagen crosslinking in patients with homocystinuria. Biochim Biophys Acta 1315, 159-162.
59. Kang A & Trelstad R (1973) Collagen defect in Homocystinuria. J Clin Invest 52, 2571-2578.
60. Thaler R, Agsten M, Spitzer S et al. (2011) Homocysteine suppresses the expression of the collagen cross-linker lysyl oxidase involving IL-6, Fli1, and epigenetic DNA methylation. J Biol Chem 286, 5578-5588.
61. Saito M, Fujii K & Marumo K (2006) Degree of mineralization-related collagen crosslinking in the femoral neck cancellous bone in cases of hip fracture and controls. Calcif Tissue Int 79, 160-168.
62. Herrmann M, Widmann T, Colaianni G et al. (2005) Increased osteoclast activity in the presence of increased homocysteine concentrations. Clin Chem 51, 2348-2353.
63. Koh J, Lee Y, Kim Y et al. (2006) Homocysteine enhances bone resorption by stimulation of osteoclast formation and activity through increased intracellular ROS generation. J Bone Miner Res 21, 1003-1011.
64. Kim DJ, Koh J, Lee O et al. (2007) Homocysteine enhances apoptosis in human bone marrow stromal cells (vol 39, pg 582, 2006). Bone 40, 554-555.
65. Herrmann M, Kranzlin M, Pape G et al. (2005) Relation of homocysteine, biochemical bone markers, and bone mineral density in peri- and postmenopausal women. Bone 36, S338-S338.
66. McLean RR & Hannan MT (2007) B vitamins, homocysteine, and bone disease: epidemiology and pathophysiology. Curr Osteoporos Rep 5, 112-119.
67. Tyagi N, Kandel M, Munjal C et al. (2011) Homocysteine mediated decrease in bone blood flow and remodeling: role of folic acid. J Orthopaed Res 29, 1511-1516.
68. 12 and physical performance in older persons. Eur J Clin Nutr 66, 174-181.
69. Swart KMA, Enneman AW, van Wijngaarden JP et al. (2013) Homocysteine and the methylenetetrahydrofolate reductase 677C ->T polymorphism in relation to muscle mass and strength, physical performance and postural sway. Eur J Clin Nutr 67, 743-748.
70. 12 and homocysteine to vertebral bone mineral density change in postmenopausal women. A five-year longitudinal evaluation. Bone 42, 314-320.
71. Holstein JH, Herrmann M, Splett C et al. (2009) Low serum folate and vitamin B-6 are associated with an altered cancellous bone structure in humans. Am J Clin Nutr 90, 1440-1445.
72. Enneman AW, van der Velde N, de Jonge R et al. The association between plasma homocysteine levels, methylation capacity and incident osteoporotic fractures. Bone 50, 1401-1405.
73. Vaes BLT, Lute C, van der Woning SP et al. (2010) Inhibition of methylation decreases osteoblast differentiation via a non-DNA-dependent methylation mechanism. Bone 46, 514-523.
74. Holstein JH, Herrmann M, Splett C et al. (2011) High bone concentrations of homocysteine are associated with altered bone morphology in humans. Br J Nutr 106, 378-382.
75. Carmel R, Lau K, Baylink D et al. (1988) Cobalamin and osteoblast-specific proteins. N Engl J Med 319, 70-75.
76. Kim G, Kim C, Park J et al. (1996) Effects of vitamin B-12 on cell proliferation and cellular alkaline phosphatase activity in human bone marrow stromal osteoprogenitor cells and UMR106 osteoblastic cells. Metab-Clin Exp 45, 1443-1446.
77. Merriman NA, Putt ME, Metz DC et al. (2010) Hip fracture risk in patients with a diagnosis of Pernicious anemia. Gastroenterology 138, 1330-1337.
78. 6 deficiency. Can J Physiol Pharmacol 78, 904-911.
79. Green T, McMahon J, Skeaff C et al. (2007) Lowering homocysteine with B vitamins has no effect on biomarkers of bone turnover in older persons: a 2-y randomized controlled trial. Am J Clin Nutr 85, 460-464.
80. Herrmann M, Umanskaya N, Traber L et al. (2007) The effect of B-vitamins on biochemical bone turnover markers and bone mineral density in osteoporotic patients: a 1-year double blind placebo controlled trial. Clin Chem Lab Med 45, 1785-1792.
81. Bird T & Levene C (1982) Lysyl oxidase - evidence that pyridoxal-phosphate is a cofactor. Biochem Biophys Res Commun 108, 1172-1180.
82. Masse P, Rimnac C, Yamauchi M et al. (1996) Pyridoxine deficiency affects biomechanical properties of chick tibial bone. Bone 18, 567-574.
83. Green PH & Jabri B (2003) Coeliac disease. Lancet 362, 383-391.
84. Larussa T, Suraci E, Nazionale I et al. (2012) Bone mineralization in celiac disease. Gastroenterol Res Pract. vol. 2012, Article ID 198025. doi:10.1155/2012/198025.
85. Pazianas M, Butcher G, Subhani J et al. (2005) Calcium absorption and bone mineral density in celiacs after long term treatment with gluten-free diet and adequate calcium intake. Osteoporos Int 16, 56-63.
86. Corazza G, Disario A, Cecchetti L et al. (1995) Bone mass and metabolism in patients with celiac-disease. Gastroenterology 109, 122-128.
87. Olmos M, Antelo M, Vazquez H et al. (2008) Systematic review and meta-analysis of observational studies on the prevalence of fractures in coeliac disease. Dig Liver Dis 40, 46-53.
88. Tilg H, Moschen AR, Kaser A et al. (2008) Gut, inflammation and osteoporosis: basic and clinical concepts. Gut 57, 684-694.
89. Fiore CE, Pennisi P, Ferro G et al. (2006) Altered osteoprotegerin/RANKL ratio and low bone mineral density in celiac patients on long-term treatment with gluten-free diet. Hormone Metab Res 38, 417-422.
90. Dickey W, Ward M, Whittle CR et al. (2008) Homocysteine and related B-vitamin status in coeliac disease: effects of gluten exclusion and histological recovery. Scand J Gastroenterol 43, 682-688.