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 B12 (B12) and B6 (B6) deficiencies. We hypothesized that folate, B12 and B6 deficiencies stimulate OC activity.


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).


CONCLUSIONS
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.
Herrmann
Markus
M
Department of Clinical Chemistry and Laboratory Medicine, University Hospital of Saarland, Homburg/Saar, Germany. markusherr@aol.com
Schmidt
Johannes
J
Umanskaya
Natascha
N
Colaianni
Graziana
G
Al Marrawi
Fuad
F
Widmann
Thomas
T
Zallone
Alberta
A
Wildemann
Britt
B
Herrmann
Wolfgang
W
D000135:Acid Phosphatase / Q000378:metabolism; D000328:Adult; D001862:Bone Resorption; D056657:Cathepsin K; D002403:Cathepsins / Q000378:metabolism; D002478:Cells, Cultured; D003804:Dentin; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D010010:Osteoclasts / Q000187:drug effects* / Q000201:enzymology; D000071681:Tartrate-Resistant Acid Phosphatase; D014805:Vitamin B 12 / Q000494:pharmacology*; D025101:Vitamin B 6 / Q000494:pharmacology*
D007527:Isoenzymes; D025101:Vitamin B 6; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase; D002403:Cathepsins; C534130:CTSK protein, human; D056657:Cathepsin K; D014805:Vitamin B 12