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

doi:10.1007/s00223-009-9244-8

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

Research output: Contribution to Journal › Article › Academic › peer-review

Abstract

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 language	Undefined/Unknown
Pages (from-to)	413-422
Journal	Calcified Tissue International
Volume	84
Issue number	5
DOIs	https://doi.org/10.1007/s00223-009-9244-8
Publication status	Published - 2009

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@article{272fd152e7774ea5bf2d61a73e9a2e69,

title = "Vitamin B-12 deficiency stimulates osteoclastogenesis via increased homocysteine and methylmalonic acid",

abstract = "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 hMSCosteoblast differentiation. We further studied the effect of B12, Hcy, and MMA on the formation of multinucleated tartrate-resistant acid phosphatase-positive osteoclasts frommouse 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 increasedMMA and Hcy levels",

author = "B.L.T. Vaes and C. Lute and H.J. Blom and N. Bravenboer and {de Vries}, T.J. and V. Everts and R.A. Dhonukshe-Rutten and M. M{\"u}ller and {de Groot}, L.C.P.G.M. and W.T. Steegenga",

year = "2009",

doi = "10.1007/s00223-009-9244-8",

language = "Undefined/Unknown",

volume = "84",

pages = "413--422",

journal = "Calcified Tissue International",

issn = "0171-967X",

publisher = "Springer New York",

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TY - JOUR

T1 - Vitamin B-12 deficiency stimulates osteoclastogenesis via increased homocysteine and methylmalonic acid

AU - Vaes, B.L.T.

AU - Lute, C.

AU - Blom, H.J.

AU - Bravenboer, N.

AU - de Vries, T.J.

AU - Everts, V.

AU - Dhonukshe-Rutten, R.A.

AU - Müller, M.

AU - de Groot, L.C.P.G.M.

AU - Steegenga, W.T.

PY - 2009

Y1 - 2009

N2 - 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 hMSCosteoblast differentiation. We further studied the effect of B12, Hcy, and MMA on the formation of multinucleated tartrate-resistant acid phosphatase-positive osteoclasts frommouse 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 increasedMMA and Hcy levels

AB - 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 hMSCosteoblast differentiation. We further studied the effect of B12, Hcy, and MMA on the formation of multinucleated tartrate-resistant acid phosphatase-positive osteoclasts frommouse 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 increasedMMA and Hcy levels

U2 - 10.1007/s00223-009-9244-8

DO - 10.1007/s00223-009-9244-8

M3 - Article

SN - 0171-967X

VL - 84

SP - 413

EP - 422

JO - Calcified Tissue International

JF - Calcified Tissue International

IS - 5

ER -