Vitamin B-12 deficiency stimulates osteoclastogenesis via increased homocysteine and methylmalonic acid

B.L.T. Vaes, C. Lute, H.J. Blom, N. Bravenboer, T.J. de Vries, V. Everts, R.A. Dhonukshe-Rutten, M. Müller, L.C.P.G.M. de Groot, W.T. Steegenga

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    The risk of nutrient deficiencies increases with age in our modern Western society, and vitamin B12 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 B12, Hcy, and MMA on differentiation and activity of bone cells. B12 deficiency did not affect the onset of osteoblast differentiation, maturation, matrix mineralization, or adipocyte differentiation from human mesenchymal stem cells (hMSCs). B12 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 B12, Hcy, and MMA on the formation of multinucleated tartrate-resistant acid phosphatase-positive osteoclasts from
    mouse bone marrow. We observed that B12 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 B12 deficiency may lead to decreased bone mass by increased osteoclast formation due to increased
    MMA and Hcy levels
    Original languageUndefined/Unknown
    Pages (from-to)413-422
    JournalCalcified Tissue International
    Issue number5
    Publication statusPublished - 2009

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