Low bone mineral density and bone mineral content are associated with low cobalamin status in adolescents

Dhonukshe-Rutten, R.A.M.; Dusseldorp, M. van; Schneede, Jörn; Groot, Lisette C. P. G. M. de; Staveren, W.A. van

doi:10.1007/s00394-004-0531-x

Cited by 50 publications

(37 citation statements)

References 26 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%

“…We and others have previously shown that B 12 deficiency and increased Hcy and MMA levels are associated with impaired bone health in the elderly [6,8,9,14,21]. In order to elucidate the molecular mechanism behind these clinical observations, we now examined the effects of B 12 , Hcy, and MMA on the differentiation of bone marrow cell cultures.…”

Section: Discussionmentioning

confidence: 99%

“…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].…”

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confidence: 99%

“…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]. Together, these data suggest that B 12 , Hcy, and MMA are important factors in the development of osteoporosis.…”

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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%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Vitamin B12 Deficiency Stimulates Osteoclastogenesis via Increased Homocysteine and Methylmalonic Acid

et al. 2009

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“…Considering the potential association between vitamin B12 and bone health, it can be suggested that vegetarians may be particularly prone to disturbances in bone metabolism (20). However, studies have reported conflicting data regarding BMD in vegetarians (20)(21)(22)(23)(24). The same holds true for bone turnover markers (BTMs).…”

Section: Introductionmentioning

confidence: 99%

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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Cobalamin Deficiency

Herrmann

Obeid

2011

Subcellular Biochemistry

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Cobalamin (Cbl, vitamin B12) consists of a corrinoid structure with cobalt in the centre of the molecule. Neither humans nor animals are able to synthesize this vitamin. Foods of animal source are the only natural source of cobalamin in human diet. There are only two enzymatic reactions in mammalian cells that require cobalamin as cofactor. Methylcobolamin is a cofactor for methionine synthase. The enzyme methylmalonyl-CoA-mutase requires adenosylcobalamin as a cofactor. Therefore, serum concentrations of homocysteine (tHcy) and methylmalonic acid (MMA) will increase in cobalamin deficiency. The cobalamin absorption from diet is a complex process that involves different proteins: haptocorrin, intrinsic factor and transcobalamin (TC). Cobalamin that is bound to TC is called holotranscobalamin (holoTC) which is the metabolically active vitamin B12 fraction. HoloTC consists 6 and 20% of total cobalamin whereas 80% of total serum cobalamin is bound to another binding protein, haptocorrin. Cobalamin deficiency is common worldwide. Cobalamin malabsorption is common in elderly subjects which might explain low vitamin status. Subjects who ingest low amount of cobalamin like vegetarians develop vitamin deficiency. No single parameter can be used to diagnose cobalamin deficiency. Total serum cobalamin is neither sensitive nor it is specific for cobalamin deficiency. This might explain why many deficient subjects would be overlooked by utilizing total cobalamin as status marker. Concentration of holotranscobalamin (holoTC) in serum is an earlier marker that becomes decreased before total serum cobalamin. Concentrations of MMA and tHcy increase in blood of cobalamin deficient subjects. Despite limitations of these markers in patients with renal dysfunction, concentrations of MMA and tHcy are useful functional markers of cobalamin status. The combined use of holoTC and MMA assays may better indicate cobalamin status than either of them. Because Cbl deficiency is a risk factor for neurodegenerative diseases an early diagnosis of a low B12 status is required which should be followed by an effective treatment in order to prevent irreversible damages.

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Low bone mineral density and bone mineral content are associated with low cobalamin status in adolescents

Cited by 50 publications

References 26 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

Cobalamin Deficiency

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