The association of homocysteine and its determinants MTHFR genotype, folate, vitamin B12 and vitamin B6 with bone mineral density in postmenopausal British women

Baines, Malcolm G.; Kredan, Mahmud B.; Usher, J.; Davison, Andrew S.; Higgins, George M.; Taylor, W. H.; West, Christopher R.; Fraser, William D.; Ranganath, L.R.

doi:10.1016/j.bone.2006.10.008

Cited by 75 publications

(53 citation statements)

References 32 publications

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“…Similarly, in study of Golbahar et al [17] plasma folate was one of the main predictors explaining 3.0 and 1.7% of variance of the BMD at femoral neck and lumbar spine, respectively. Based on presented results Cagnacci et al [18] and Baines et al [19] concluded a major association between folate and bone mineralization.…”

Section: Discussionmentioning

confidence: 95%

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Bone mineral density is not associated with homocysteine level, folate and vitamin B12 status

Rumbak

Žižić

Sokolić

et al. 2011

Arch Gynecol Obstet

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Section: Discussionmentioning

confidence: 95%

“…Low serum folate was found to be a significant risk factor for osteoporosis in the group of postmenopausal British women [19].…”

Section: Introductionmentioning

confidence: 99%

Bone mineral density is not associated with homocysteine level, folate and vitamin B12 status

Rumbak

Žižić

Sokolić

et al. 2011

Arch Gynecol Obstet

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“…(15) Clinical studies suggest that low folate levels are associated with low BMD and increased fracture risk. (16)(17)(18)(19)(20) For B 12 , existing studies are equivocal. (16,(21)(22)(23) The only experimental data available are derived from cell culture studies providing evidence that folate, B 12 , and B 6 deficiencies stimulate osteoclasts but not osteoblasts through an accumulation of HCY.…”

Section: Introductionmentioning

confidence: 99%

Experimental Folate and Vitamin B12 Deficiency Does Not Alter Bone Quality in Rats

Herrmann

Wildemann

Wagner

et al. 2009

Journal of Bone and Mineral Research

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Hyperhomocysteinemia (HHCY) has been linked to fragility fractures and osteoporosis. Folate and vitamin B 12 deficiencies are among the main causes of HHCY. However, the impact of these vitamins on bone health has been poorly studied. This study analyzed the effect of folate and vitamin B 12 deficiency on bone in rats. We used two groups of rats: a control group (Co, n = 10) and a vitamin-deficient group (VitDef, n = 10). VitDef animals were fed for 12 wk with a folate-and vitamin B 12 -free diet. Co animals received an equicaloric control diet. Tissue and plasma concentrations of homocysteine (HCY), S-adenosyl-homocysteine (SAH), and S-adenosyl-methionine (SAM) were measured. Bone quality was assessed by biomechanical testing (maximum force of an axial compression test; F max ), histomorphometry (bone area/total area; B.Ar./ T.Ar.], and the measurement of biochemical bone turnover markers (osteocalcin, collagen I C-terminal crosslaps [CTX]). VitDef animals developed significant HHCY (Co versus VitDef: 6.8 ± 2.7 versus 61.1 ± 12.8 mM, p < 0.001) that was accompanied by a high plasma concentration of SAH (Co versus VitDef: 24.1 ± 5.9 versus 86.4 ± 44.3 nM, p < 0.001). However, bone tissue concentrations of HCY, SAH, and SAM were similar in the two groups. Fmax, B.Ar./T.Ar., OC, and CTX did not differ between VitDef and Co animals, indicating that bone quality was not affected. Folate and vitamin B 12 deficiency induces distinct HHCY but has no effect on bone health in otherwise healthy adult rats. The unchanged HCY metabolism in bone is the most probable explanation for the missing effect of the vitamin-free diet on bone.

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“…Several studies have reported that low plasma B 12 levels are associated with reduced bone quality [5,8,9,13,14], but this relation has not been observed by others [15][16][17]. More consistently, however, are the observations that increased Hcy may be a predictive factor for fracture risk [13][14][15][18][19][20][21]. Also, elevated MMA levels have been associated with osteoporosis in the elderly [14] and low bone mineral density (BMD) in adolescents [6].…”

mentioning

confidence: 99%

Vitamin B12 Deficiency Stimulates Osteoclastogenesis via Increased Homocysteine and Methylmalonic Acid

et al. 2009

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The risk of nutrient deficiencies increases with age in our modern Western society, and vitamin B 12 deficiency is especially prevalent in the elderly and causes increased homocysteine (Hcy) and methylmalonic acid (MMA) levels. These three factors have been recognized as risk factors for reduced bone mineral density and increased fracture risk, though mechanistic evidence is still lacking. In the present study, we investigated the influence of B 12 , Hcy, and MMA on differentiation and activity of bone cells. B 12 deficiency did not affect the onset of osteoblast differentiation, maturation, matrix mineralization, or adipocyte differentiation from human mesenchymal stem cells (hMSCs). B 12 deficiency caused an increase in the secretion of Hcy and MMA into the culture medium by osteoblasts, but Hcy and MMA appeared to have no effect on hMSC osteoblast differentiation. We further studied the effect of B 12 , Hcy, and MMA on the formation of multinucleated tartrate-resistant acid phosphatase-positive osteoclasts from mouse bone marrow. We observed that B 12 did not show an effect on osteoclastogenesis. However, Hcy as well as MMA were found to induce osteoclastogenesis in a dose-dependent manner. On the basis of these results, we conclude that B 12 deficiency may lead to decreased bone mass by increased osteoclast formation due to increased MMA and Hcy levels.Osteoporosis is a complex multifactorial disease with a strong genetic component, but lifestyle factors are also important for maintenance of bone mass. Nutrition is one of the factors that contributes to bone health. During the first decades of life, adequate intake of calcium and vitamin D is essential to establish peak bone mass (see [1,2] and references therein). It has also been observed that nutritional deficiencies can cause impaired growth and skeletal abnormalities during childhood [3], while in adults inadequate intake of nutrients such as proteins, vitamins, and minerals has been associated with loss of bone quality [2,4]. Nutritional deficiency is very common in the elderly, emphasizing that adequate nutrient intake may slow down the age-related loss of bone mass.A challenge in nutrition research is to identify food components that contribute to the maintenance of bone health. During the last years, vitamin B 12 has gained particular attention since a number of epidemiological studies have reported a correlation between B 12 status and bone quality and fracture risk [5][6][7][8][9]. The micronutrient B 12 is involved as a cofactor in two enzymatic reactions [10]. The enzyme methionine synthase requires B 12 for the remethylation of homocysteine (Hcy) into methionine. The other enzyme dependent on B 12 is methylmalonyl-CoA mutase, which catalyzes the conversion of methylmalonyl-CoA into succinyl-CoA. As a consequence of B 12 deficiency, these

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The association of homocysteine and its determinants MTHFR genotype, folate, vitamin B12 and vitamin B6 with bone mineral density in postmenopausal British women

Cited by 75 publications

References 32 publications

Bone mineral density is not associated with homocysteine level, folate and vitamin B12 status

Bone mineral density is not associated with homocysteine level, folate and vitamin B12 status

Experimental Folate and Vitamin B12 Deficiency Does Not Alter Bone Quality in Rats

Vitamin B12 Deficiency Stimulates Osteoclastogenesis via Increased Homocysteine and Methylmalonic Acid

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