Protective effect of folic acid on cyclosporine-induced bone loss in rats

Transpl Int. 2012 Jan;25(1):127-33. doi: 10.1111/j.1432-2277.2011.01375.x. Epub 2011 Nov 1.


Hyperhomocysteinemia is seen in patients with decreased bone mineral density. Cyclosporine can cause alveolar bone loss and osteopenia. It is also associated with elevated serum homocysteine levels. We aimed to investigate the effect of cyclosporine on serum homocysteine level, bone volume, and bone density, and determine whether folic acid had a protective effect against bone loss. In an experimental study, 40 male Sprague-Dawley rats were randomly assigned to five groups and received dietary supplementation for 6 weeks with olive oil (Group A), cyclosporine (Group B), folic acid (Group C), and cyclosporine plus folic acid (Group D), or no supplementation (Group F, control). Serum homocysteine, calcium, alkaline phosphatase, total bone volume, periodontal ligament volume, and volume density of bone were compared between groups. Mean serum homocysteine level (10.84 ± 0.93 μmol/l) was significantly higher in group B (cyclosporine supplementation) compared with the other groups (P = 0.001). Mean total mandibular volume was 46.3 ± 13.6 mm(3) in rats treated with cyclosporine, 80.4 ± 15.70 mm(3) in rats treated with folic acid (P = 0.004), and 73.9 ± 21.3 mm(3) in rats treated with cyclosporine plus folic acid (P = 0.028). In our experimental model, cyclosporine increased serum homocysteine levels and decreased bone volume and density. Folic acid may have a preventive role against bone loss in rats treated with cyclosporine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animal Feed
  • Animals
  • Bone Density / drug effects
  • Cyclosporine / adverse effects*
  • Cyclosporine / pharmacology
  • Folic Acid / metabolism
  • Folic Acid / pharmacology*
  • Homocysteine / blood
  • Immunosuppressive Agents / adverse effects*
  • Immunosuppressive Agents / pharmacology
  • Male
  • Models, Biological
  • Models, Statistical
  • Rats
  • Rats, Sprague-Dawley


  • Immunosuppressive Agents
  • Homocysteine
  • Cyclosporine
  • Folic Acid