Homocysteine and Vitamin B12 Status Relate to Bone Turnover Markers, Broadband Ultrasound Attenuation, and Fractures in Healthy Elderly People

Dhonukshe-Rutten, R.A.M.; Pluijm, Saskia M. F.; Groot, Lisette C. P. G. M. de; Lips, Paul; Smit, Johannes H.; Staveren, W.A. van

doi:10.1359/jbmr.050202

Cited by 194 publications

(146 citation statements)

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“…To exclude the possibility that substantial baseline levels of B 12 were present in the culture medium, a quantitative measurement of B 12 levels was carried out. Baseline levels were lower than 15 pM, which is far below the B 12 deficiency level of 200 pM [13]. Culturing hMSCs in osteogenic differentiation medium resulted in a homogeneous population of ALP-positive cells after 9 days of culture, as visualized by cytochemical staining for ALP (Fig.…”

Section: Vitamin B 12 Deficiency Does Not Affect Osteoblast Differentmentioning

confidence: 88%

“…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].…”

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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: Vitamin B 12 Deficiency Does Not Affect Osteoblast Differentmentioning

confidence: 88%

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confidence: 99%

Vitamin B12 Deficiency Stimulates Osteoclastogenesis via Increased Homocysteine and Methylmalonic Acid

et al. 2009

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“…In 2004, two landmark studies performed in the Netherlands and the USA produced consistent findings in terms of the magnitude of increased risk of fracture associated with mild elevations in homocysteine (36,37) . In subsequent years, further studies from the USA, the Netherlands and Norway similarly demonstrated increases in fracture risk associated with elevated homocysteine concentrations (31)(32)(33)35) . Confirming these findings, a recent meta-analysis involving nine prospective studies and 14 863 participants reported a relative risk of 1.59 (95 % CI 1.30, 1.96) and 1.67 (95 % CI 1.17, 2.38) for all fractures and hip fractures, respectively, in those within the highest homocysteine quartile compared with the lowest (30) .…”

Section: Evidence From Observational Studiesmentioning

confidence: 95%

“…In the past decade, numerous large observational studies have provided evidence to support a role for homocysteine and/or low B-vitamin status in fracture risk (Table 1) (12,(29)(30)(31)(32)(33)(34)(35)(36)(37) . In 2004, two landmark studies performed in the Netherlands and the USA produced consistent findings in terms of the magnitude of increased risk of fracture associated with mild elevations in homocysteine (36,37) .…”

Section: Evidence From Observational Studiesmentioning

confidence: 99%

“…Most recently, a doseresponse meta-analysis including eight observational studies and 11 511 participants estimated a 4 % increase in fracture risk for every 1 μmol/l increase in homocysteine concentration (12) . Given the close metabolic relationship of the B-vitamins with homocysteine, studies have also demonstrated inverse associations between the status of the B-vitamins, folate, vitamins B 12 and B 6 and fracture risk in large cohorts of men and women (29,(33)(34)(35) .…”

Section: Evidence From Observational Studiesmentioning

confidence: 99%

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

et al. 2014

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Osteoporosis, a metabolic skeletal disease characterised by decreased bone mass and increased fracture risk, is a growing public health problem. Among the various risk factors for osteoporosis, calcium and vitamin D have well-established protective roles, but it is likely that other nutritional factors are also implicated. This review will explore the emerging evidence supporting a role for certain B-vitamins, homocysteine and the 677C→T polymorphism in the gene encoding the folate-metabolising enzyme methylenetetrahydrofolate reductase, in bone health and disease. The evidence, however, is not entirely consistent and as yet no clear mechanism has been defined to explain the potential link between B-vitamins and bone health. Coeliac disease, a common condition of malabsorption, induced by gluten ingestion in genetically susceptible individuals, is associated with an increased risk both of osteoporosis and inadequate B-vitamin status. Given the growing body of evidence linking low bone mineral density and/or increased fracture risk with low B-vitamin status and elevated homocysteine, optimal B-vitamin status may play an important protective role against osteoporosis in coeliac disease; to date, no trial has addressed this possible link.

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