Accumulation of homocysteine by decreasing concentrations of folate, vitamin B12 and B6 does not influence the activity of human osteoblasts in vitro

Herrmann, Markus; Umanskaya, Natalia; Wildemann, Britt; Colaianni, Graziana; Schmidt, Johannes Peter; Widmann, Thomas; Zallone, Alberta; Herrmann, Wolfgang

doi:10.1016/j.cca.2007.06.016

Cited by 20 publications

(22 citation statements)

References 28 publications

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“…A stimulating effect on ALP expression was reported in human rib-derived osteoprogenitors [25], rat osteosarcoma cells [25], and chicken calvaria-derived osteoblasts [22]. More recently, it was shown that simultaneous reduction of B 12 , B 6 , and folic acid levels had no influence on ALP expression in human osteoblasts [24].…”

Section: Discussionmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

“…A number of studies have described the effects of B 12 and Hcy on osteoblasts and osteoclasts [22][23][24][25][26][27]. Here, we analyzed the effects of B 12 , Hcy, and MMA on human mesenchymal stem cells (hMSCs), the precursor cells of both osteoblasts and adipocytes.…”

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confidence: 99%

Vitamin B12 Deficiency Stimulates Osteoclastogenesis via Increased Homocysteine and Methylmalonic Acid

et al. 2009

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“…This suggests a causal relationship between decreased B-vitamins and bone degradation (38). However, no such effects have been observed for human osteoblasts (11). While results for osteoblasts are conflicting, existing data support a regulatory role for vitamin B12 in bone resorption.…”

Section: Discussionmentioning

confidence: 99%

“…Cell culture experiments using human osteoclasts and osteoblasts revealed a distinct increase in osteoclast activity in the presence of high tHcy and low vitamin B12, B6, and folate concentrations in the culture medium. This was indicated by significant increases in osteoclastic resorption, tartrate resistant acid phosphatase (TRAP) and cathepsin K activities (10,11). Osteoblast activity was not affected by changes in vitamin B12, B6, and folate concentrations in the culture medium (11).…”

Section: Introductionmentioning

confidence: 99%

“…This was indicated by significant increases in osteoclastic resorption, tartrate resistant acid phosphatase (TRAP) and cathepsin K activities (10,11). Osteoblast activity was not affected by changes in vitamin B12, B6, and folate concentrations in the culture medium (11). The importance of vitamin B12 for bone health is supported by clinical data where patients with low vitamin B12 status or pernicious anemia exhibited low BMD, increased fracture rates and accelerated bone turnover that could be improved by supplementations with vitamin B12 (12)(13)(14).…”

Section: Introductionmentioning

confidence: 99%

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Enhanced bone metabolism in vegetarians – the role of vitamin B12 deficiency

Herrmann

Obeid²,

Schorr³

et al. 2009

Clinical Chemistry and Laboratory Medicine

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Background: Vitamin B12 deficiency and bone fractures are common in vegetarians. However, a direct relationship between vitamin B12 status and bone metabolism in vegetarians has not been tested sufficiently. Methods: Our study included 96 vegetarians (23 German vegans, and 54 German and 19 Indian lacto-, lacto-ovo-vegetarians) and 89 omnivores (Germans and Asian-Indian immigrants in Oman). Blood concentrations of total vitamin B12, holotranscobalamin (holoTC), 25OH-vitamin D (25(OH)D), total homocysteine (tHcy), methylmalonic acid (MMA), and the bone turnover markers (BTMs) bone alkaline phosphatase (BAP), osteocalcin (OC), pro-collagen type I N-terminal peptide (PINP) and C-terminal telopeptides of collagen I (CTx) were measured. Results: Vegetarians from both population groups exhibited significantly higher concentrations of tHcy, MMA, folate, and BAP, but lower concentrations of holoTC and cobalamin compared with omnivores from the same population. Additionally, German vegetarians had higher circulating activities of BAP as well as higher CTx, OC, and PINP compared with their omnivorous controls. HoloTC and MMA were correlated with OC, CTx and BAP. Subjects with low vitamin B12 status (holoTC F35 pmol/L and MMA

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Low holotranscobalamin and cobalamins predict incident fractures in elderly men: the MrOS Sweden

et al. 2013

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Accumulation of homocysteine by decreasing concentrations of folate, vitamin B12 and B6 does not influence the activity of human osteoblasts in vitro

Cited by 20 publications

References 28 publications

Vitamin B12 Deficiency Stimulates Osteoclastogenesis via Increased Homocysteine and Methylmalonic Acid

Vitamin B12 Deficiency Stimulates Osteoclastogenesis via Increased Homocysteine and Methylmalonic Acid

Enhanced bone metabolism in vegetarians – the role of vitamin B12 deficiency

Low holotranscobalamin and cobalamins predict incident fractures in elderly men: the MrOS Sweden

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