Vitamin B12 Deficiency Stimulates Osteoclastogenesis via Increased Homocysteine and Methylmalonic Acid

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 bon...

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Bibliographic Details
Published in:Calcified tissue international 2009-05, Vol.84 (5), p.413-422
Main Authors: 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., Steegenga, Wilma T.
Format: Article
Language:English
Subjects:
Biochemistry
Biomedical and Life Sciences
Bone density
bone-mineral density
Cell Biology
Cell growth
elderly-women
Endocrinology
hip fracture
in-vitro
Life Sciences
older persons
Orthopedics
Osteoporosis
pernicious-anemia
plasma homocysteine
postmenopausal women
randomized controlled-trial
turnover markers
Vitamin B
Vitamin deficiency
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Summary: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.
ISSN:0171-967X
1432-0827
DOI:10.1007/s00223-009-9244-8