Accumulation of homocysteine by decreasing concentrations of folate, vitamin B12 and B6 does not influence the activity of human osteoblasts in vitro

Clin Chim Acta. 2007 Sep;384(1-2):129-34. doi: 10.1016/j.cca.2007.06.016. Epub 2007 Jul 4.


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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calcification, Physiologic
  • Cells, Cultured
  • Folic Acid / metabolism*
  • Homocysteine / metabolism*
  • Humans
  • Osteoblasts / metabolism
  • Osteoblasts / physiology*
  • Osteocalcin / metabolism
  • Peptide Fragments / metabolism
  • Procollagen / metabolism
  • Vitamin B 12 / metabolism*
  • Vitamin B 6 / metabolism*


  • Peptide Fragments
  • Procollagen
  • procollagen Type I N-terminal peptide
  • Homocysteine
  • Osteocalcin
  • Vitamin B 6
  • Folic Acid
  • Vitamin B 12