Stimulation of osteoclast activity by low B-vitamin concentrations

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• 作者：Markus Herrmann ; Johannes Schmidt ; Natascha Umanskaya ; Graziana Colaianni ; Fuad Al Marrawi ; Thomas Widmann ; Alberta Zallone ; Britt Wildemann ; Wolfgang Herrmann
• 关键词：Folate ; Vitamin B₁₂ ; Vitamin B₆ ; Homocysteine ; Osteoclast
• 刊名：Bone
• 出版年：2007
• 期刊代码：39_87563282
• 类别：med
• 出版时间：October 2007
• 卷：41
• 期：4
• 页码：584-591
• 文件大小：528 K

摘要

Homocysteine (HCY) has recently been linked to fragility fractures. Moreover, HCY activates osteoclasts (OC). Elevated HCY concentrations are mainly caused by folate, vitamin B₁₂ (B₁₂) and B₆ (B₆) deficiencies. We hypothesized that folate, B₁₂ and B₆ deficiencies stimulate OC activity.

Materials and methods

OC were cultured from peripheral blood mononuclear cells (10 healthy male donors, 34 ± 5 years) for 20 days. Culture medium was conditioned with decreasing concentrations of folate, B₁₂ and B₆ (in combination or variation of only one vitamin) starting at physiologic concentrations. Moreover, we tested increasing concentrations of HCY. OC activity was measured by dentine resorption activity (DRA), tartrate-resistant acid phosphatase (TRAP) and cathepsin K (CK) activity.

Results

The combined reduction of folate, B₁₂ and B₆ stimulated DRA up to 211%(p < 0.001). This observation was confirmed by TRAP (maximum increase 24%, p < 0.001) and CK (maximum increase 24%, p < 0.001). Reduction of only one vitamin stimulated DRA up to 250%(folate: maximum increase 248%, p < 0.018; B₁₂: maximum increase 252%, p < 0.001, B₆: maximum increase 247%, p < 0.001). However, only for folate this effect could be confirmed by TRAP (maximum increase 33%, p < 0.001). HCY stimulated DRA up to 395%(p < 0.001). TRAP (maximum increase 49%, p < 0.001) and CK analyses confirmed this observation (maximum increase 50%, p < 0.001).

Conclusion

Our results demonstrate a strong stimulatory effect of low concentrations of folate, B₁₂ and B₆ on OC activity, suggesting a mechanistic role of low B-vitamin concentrations for bone degradation. Consequently, OC stimulation by low folate, B₁₂ and B₆ concentrations could be an important adverse factor for bone health.