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

Vaes, Bart L T, Lute, Carolien, Blom, Henk J, Bravenboer, Nathalie, de Vries, Teun J, Everts, Vincent, Dhonukshe-Rutten, Rosalie A, Müller, Michael, de Groot, Lisette C P G M and Steegenga, Wilma T (2009) Vitamin B(12) deficiency stimulates osteoclastogenesis via increased homocysteine and methylmalonic acid. Calcified Tissue International, 84 (5). pp. 413-422. ISSN 0171-967X

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Abstract

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.

Item Type: Article
Uncontrolled Keywords: animals,bone density,bone remodeling,bone and bones,cell differentiation,cell line,cell proliferation,dose-response relationship, drug,homocysteine,humans,male,methylmalonic acid,mice,mice, inbred c57bl,osteoclasts,osteoporosis,up-regulation,vitamin b 12,vitamin b 12 deficiency
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
Depositing User: Pure Connector
Date Deposited: 10 Jun 2014 21:40
Last Modified: 14 Sep 2020 07:04
URI: https://ueaeprints.uea.ac.uk/id/eprint/47704
DOI: 10.1007/s00223-009-9244-8

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