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Epidemiological studies
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| Baines et al., 20071010 Atkins D, Best D, Briss PA, Eccles M, Falck-Ytter Y, Flottorp S, et al.; Grade Working Group. Grading quality of evidence and strength of recommendations. BMJ. 2004; 328(7454):1490.
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Cross-sectional observational study 328 postmenopausal British women |
Plasma homocysteine, serum levels of vitamins B6, B9 and B12, genotype of the MTHFR enzyme, and BMD |
– |
Folate levels were significantly associated with BMD (p=0.02), but vitamin B6 and B12 were not (p=0.91 and p=0.82, respectively) |
Moderate |
| Gjesdal, et al., 20071616 Baines M, Kredan MB, Usher J, Davison A, Higgins G, Taylor W, et al. The association of homocysteine and its determinants MTHFR genotype, folate, vitamin B12 and vitamin B6 with bone mineral density in postmenopausal British women. Bone. 2007; 40(3):730-6.
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Prospective longitudinal observational study 4,766 elderly Norwegian men and women, aged 65-67 years, for 13 years |
Plasma levels of homocysteine, vitamins B9 and B12, polymorphism of genotypes 677C ® T and 1298A ® C MTHFR, and risk of fractures |
– |
Vitamin B12 and the MTHFR genotype were not associated with hip fractures
Homocysteine increased the risk of fracture in both genders. Only among women there was an inverse association between folate levels and fracture risk |
High |
| Yazdanpanah et al., 20071818 Gjesdal CG, Vollset SE, Ueland PM, Refsum H, Meyer HE, Tell GS. Plasma homocysteine, folate, and vitamin B12 and the risk of hip fracture: the hordaland homocysteine study. J Bone Miner Res. 2007; 22(5):747-56.
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Prospective longitudinal observational study 5304 Dutch men and women aged 55 or over for 6 to 7 years |
Association of dietary intake of vitamins B2, B6, B9 and B12 with BMD and risk of fractures |
– |
There was no association of vitamins B9 and B12 with BMD and the risk of fractures
Positive association of vitamins B6 and B2 with BMD (b=0.09, p=1 × 10-8 b=0.06, p=0.002, respectively)
Pyridoxine intake was inversely correlated with fracture risk |
Low |
| Cagnacci et al., 20081919 Yazdanpanah N, Zillikens MC, Rivadeneira F, de Jong R, Lindemans J, Uitterlinden AG, et al. Effect of dietary B vitamins on BMD and risk of fracture in elderly men and women: the Rotterdam Study. Bone. 2007; 41(6):987-94.
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Prospective longitudinal observational study 117 postmenopausal women, aged 54 years on average, for 5 years |
Association between serum levels of vitamins B9 and B12, homocysteine and BMD |
– |
There was no association of vitamin B12 and homocysteine with BMD
The rate of BMD variation over the 5 years correlated positively with serum folate levels (p=0.011) |
Low |
| McLean et al., 200833 McLean RR, Jacques PF, Selhub J, Fredman L, Tucker KL, Samelson EJ, et al. Plasma B vitamins, homocysteine, and their relation with bone loss and hip fracture in elderly men and women. J Clin Endocrinol Metab. 2008; 93(6):2206-12.
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Longitudinal observational study 1002 men and women with mean age of 75 years for 4 years |
Plasma concentrations of vitamins B6, B9 and B12, and homocysteine with bone loss and risk of hip fracture in elderly men and women |
– |
Low concentrations of vitamins B12 and B6 were associated with increased risk of hip fracture. Lower plasma concentration of vitamin B6 was associated with greater bone loss |
Moderate |
| Rejnmark et al., 20082020 Cagnacci A, Bagni B, Zini A, Cannoletta M, Generali M, Volpe A. Relation of folates, vitamin B12 and homocysteine to vertebral bone mineral density change in postmenopausal women. A five-year longitudinal evaluation. Bone. 2008; 42(2):314-20.
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Prospective longitudinal observational study 1,869 Danish women in perimenopause, aged between 43 and 58 years, for 10 years |
Association of dietary intake and supplementation of vitamins B2, B9 and B12 with BMD and fracture risk |
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There was no positive association between B12, B9, B2 and BMD or fracture risk. At 5 years, cross-sectional analyzes indicated that folic acid intake correlated significantly with BMD |
Low |
| Bozkurt et al., 20092121 Rejnmark L, Vestergaard P, Hermann AP, Brot C, Eiken P, Mosekilde L. 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.
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Cross-sectional observational study 178 postmenopausal Turkish women |
Relation of serum levels of homocysteine, vitamins B9 and B12 with BMD |
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Serum levels of vitamin B12, but not those of B9, were associated with osteoporosis in the lumbar spine and neck of the femur
Homocysteine levels were found to be higher in women with osteoporosis compared to normal women or those with osteopenia |
Moderate |
| Holstein et al., 20091515 Bozkurt N, Erdem M, YIlmaz E, Erdem A, Biri A, Kubatova A, et al. The relationship of homocyteine, B12 and folic acid with the bone mineral density of the femur and lumbar spine in Turkish postmenopausal women. Arch Gynecol Obstet. 2009; 280(3):381-7.
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Cross-sectional observational study 94 German women and men treated with hip arthroplasty |
Association of serum levels of homocysteine, vitamins B6, B9 and B12 with OC (bone formation marker), TRAP (bone resorption marker), BMD and trabecular thickness |
– |
There was no positive association between vitamin B12, as well as the other vitamins analyzed, and BMD or homocysteine
OC levels are lower in individuals with low levels of B-complex vitamins. Trabecular thickness is lower in individuals with low B9 concentrations. |
Moderate |
| Halıloglu et al., 20101414 Holstein JH, Herrmann M, Splett C, Herrmann W, Garcia P, Histing T, et al. Low serum folate and vitamin B-6 are associated with an altered cancellous bone structure in humans. Am J Clin Nutr. 2009; 90(5):1440-5.
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Cross-sectional observational study 120 postmenopausal women |
Relation of serum levels of homocysteine, vitamins B9 and B12 with BMD and markers of bone remodeling (BAP and CTx) |
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There was no positive association of vitamins B12 and B9 with BMD and markers of bone remodeling.
Homocysteine levels were higher in osteoporotic women but were not related to BMD |
Moderate |
| Kakehasi et al., 2012121 Rejnmark L, Vestergaard P, Hermann AP, Brot C, Eiken P, Mosekilde L. 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.
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Cross-sectional observational study 70 postmenopausal Brazilian women (50 to 79 years) |
Plasma levels of vitamin B12 and BMD |
– |
There was no association between plasma levels of vitamin B12 and BMD (p=0.93) |
Low |
| Rumbak et al., 20122222 Haliloglu B, Aksungar FB, Ilter E, Peker H, Akin FT, Mutlu N, et al. Relationship between bone mineral density, bone turnover markers and homocysteine, folate and vitamin B12 levels in postmenopausal women. Arch Gynecol Obstet. 2010; 281(4):663-8.
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Cross-sectional observational study 131 Croatian women aged between 45 and 65 years |
Relation of serum levels of vitamin B12, plasma levels of homocysteine and red blood cells and serum levels of vitamin B9 to BMD |
– |
There was no association of vitamins B12 and B9 and homocysteine with BMD |
Low |
| Dai et al., 20131717 Rumbak I, Zižić V, Sokolić L, Cvijetić S, Kajfež R, Colić Barić IC. Bone mineral density is not associated with homocysteine level, folate and vitamin B12 status. Arch Gynecol Obstet. 2012; 285(4):991-1000.
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Prospective longitudinal observational study 63154 Chinese women and men, aged between 45 and 74 years, for 13.8 years |
Association of dietary intake of vitamins B1, B2, B3, B6, B9 and B12 with the risk of hip fractures |
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Inverse relationship between dietary intake of vitamin B6 and risk of hip fracture in older women but not in men There was no association between the dietary intake of B12 and the other B vitamins and the risk of fractures |
Moderate |
| Bailey et al., 20152323 Dai Z, Wang R, Ang LW, Yuan JM, Koh WP. Dietary B vitamin intake and risk of hip fracture: the Singapore Chinese Health Study. Osteoporos Int. 2013; 24(7):2049-59.
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Cross-sectional observational study 2806 American women aged ≥ 50 years |
Association of homocysteine and vitamin B12 with BMD and risk of osteoporosis |
– |
High levels of homocysteine and methyl malonic acid were associated with increased risk of osteoporosis in the lumbar spine.
Vitamin B12 was not directly associated with BMD |
High |
| Clarke at al, 201599 Clarke M, Ward M, Dickey W, Hoey L, Molloy AM, Waldron L, et al. B-vitamin status in relation to bone mineral density in treated celiac disease patients. Scand J Gastroenterol. 2015; 50(8):975-84.
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Cross-sectional observational study 110 women and men over the age of 20 under treatment for celiac disease |
Association of nutritional status of vitamins B2, B6, B9 and B12 with BMD |
– |
Only serum levels of vitamin B12 were significantly determining for femoral and hip BMD in men but not in women |
Low |
| Bahtiri et al., 20151313 Bailey RL, Looker AC, Lu Z, Fan R, Eicher-Miller HA, Fakhouri TH, et al. B-vitamin status and bone mineral density and risk of lumbar osteoporosis in older females in the United States. Am J Clin Nutr. 2015; 102(3):687-94.
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Cross-sectional observational study 139 postmenopausal women |
Association of serum levels of homocysteine and vitamin B12 with BMD |
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Serum homocysteine levels were significantly higher in osteoporotic women than in the other groups and inversely correlated with lumbar spine and femoral neck BMD. Serum vitamin B12 levels were not associated with BMD |
Low |
| Clinical trials |
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| Gommans et al., 20132424 Bahtiri E, Islami H, Rexhepi S, Qorraj-Bytyqi H, Thaçi K, Thaçi S, et al. Relationship of homocysteine levels with lumbar spine and femur neck BMD in postmenopausal women. Acta Reumatol Port. 2015; 40(4):355-62.
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Randomized, double-blind, placebo-controlled clinical trial 8,164 patients of both sexes with recent episodes and cerebrovascular events |
Supplementation of B-complex vitamins would decrease the incidence of fractures in patients with cerebrovascular disease |
Control: N=4075 Placebo treatment: N=4089, B complex vitamins: (folic acid: 2 mg, vitamin B6: 25 mg, vitamin B12 500 µg |
Homocysteine levels were lower in the treatment group There was no association between treatment with B vitamins and fracture risk |
High |
| van Wijngaarden et al., 20142525 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.
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Randomized, double-blind, placebo-controlled clinical trial. 2,919 Dutch male and female participants, aged ≥ 65 years and high concentrations of homocysteine (12-50 µmol/L), for 2 years |
Combined vitamin B9 and B12 supplementation to prevent osteoporotic fractures |
Control: daily doses of placebo + 600 IU of vitamin D3 Treatment: daily doses of 500 µg of vitamin B12 and 400 µg of vitamin B9 + 600 IU of vitamin D3 |
There was no significant reduction in the risk of fractures between groups
In the treatment subgroup there was a reduction in fractures among participants over 80 years of age
Homocysteine levels decreased significantly in the treatment group |
High |
