Stimulation of osteoclast activity by low B-vitamin concentrations

Background: Homocysteine (HCY) has recently been linked to fragility fractures. Moreover, HCY activates osteoclasts (OC). Elevated HCY concentrations are mainly caused by folate, vitamin B-12 (B-12) and B-6 (B-6) deficiencies. We hypothesized that folate, B-12 and B-6 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, B-12 and B-6 (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, B-12 and B-6 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; B-12: maximum increase 252%, p<0.001, 136: 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, B-12 and B-6 on OC activity, suggesting a mechanistic role of low B-vitamin concentrations for bone degradation. Consequently, OC stimulation by low folate, B-12 and B-6 concentrations could be an important adverse factor for bone health. (C) 2007 Elsevier Inc. All rights reserved.