Accumulation of homocysteine by decreasing concentrations of folate, vitamin B12 and B6 does not influence the activity of human osteoblasts in vitro.
BACKGROUND
Homocysteine (HCY) has recently been linked to fragility fractures. Elevated circulating HCY is mainly caused by folate, vitamin B12 and B6 deficiencies. However, little is known about the effect of these vitamins on the activity of osteoblasts. We hypothesized that decreasing concentrations of folate, vitamin B12 and B6 decrease osteoblasts activity by accumulation of HCY.


METHODS
Osteoblasts obtained from trabecular human bone specimens of 8 donors were cultured with decreasing concentrations of folate, vitamin B12 and B6. Vitamin concentrations were modified in combination or one vitamin only (8 repetitions x 8 donors, n=64). After 14 days alkaline phosphatase (AP) activity, pro-collagen type I N-terminal peptide (PINP) and osteocalcin secretion in the supernatant was measured. After 20 days, the formation of mineralized matrix was analyzed.


RESULTS
Decreasing B-vitamin concentrations induced a significant accumulation of HCY in the supernatant reaching up to 160%. The increase in HCY was not accompanied by changes of AP, osteocalcin and PINP. Moreover, mineralized matrix formation was not affected.


CONCLUSIONS
Accumulation of HCY by decreasing concentrations of folate, vitamin B12 and B6 does not affect the activity of human osteoblasts. Consequently, other mechanisms have to be responsible for the reduced bone quality in hyperhomocysteinemic subjects.
Department of Clinical Chemistry and Laboratory Medicine, University Hospital of Saarland, D-66421 Homburg/Saar, Germany. markusherr@aol.com
Markus
M
Herrmann
Natalia
N
Umanskaya
Britt
B
Wildemann
Graziana
G
Colaianni
Johannes
J
Schmidt
Thomas
T
Widmann
Alberta
A
Zallone
Wolfgang
W
Herrmann
D002113:Calcification, Physiologic; D002478:Cells, Cultured; D005492:Folic Acid / Q000378:metabolism*; D006710:Homocysteine / Q000378:metabolism*; D006801:Humans; D010006:Osteoblasts / Q000378:metabolism / Q000502:physiology*; D015675:Osteocalcin / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D011347:Procollagen / Q000378:metabolism; D014805:Vitamin B 12 / Q000378:metabolism*; D025101:Vitamin B 6 / Q000378:metabolism*
D010446:Peptide Fragments; D011347:Procollagen; C047202:procollagen Type I N-terminal peptide; D006710:Homocysteine; D015675:Osteocalcin; D025101:Vitamin B 6; D005492:Folic Acid; D014805:Vitamin B 12