Effects of cyclosporin A on experimental new bone formation in rats

The effects of the immunosuppressive drug cyclosporin A (CsA) on bone induction by demineralized allogeneic (rat) bone matrix (DABM) and demineralized xenogeneic (rabbit) bone matrix (DXBM) were studied. Growing rats were implanted with three samples each of DABM and DXBM. Groups of eight rats were treated with 0.5 or 2 mg CsA/kg body weight for four weeks and compared with a placebo group. Cyclosporin A treatment enhanced bone induction in DABM implants by 40 to 50% at four weeks, whereas there was no difference from the control group at eight weeks. Demineralized xenogeneic bone matrix induced virtually no bone in control rats at four weeks, whereas the net bone formation increased four to five times in both groups of CsA-treated rats. At eight weeks, DXBM without CsA had induced some bone formation, and the amount was almost equal to that of DABM implants in CsA-treated groups. Also, the mineral accretion rates of DXBM were equal to DABM implants in CsA-treated rats. Cyclosporin A treatment doubled the uptake of 45Ca in the orthotopic skeleton (femora) at four weeks without affecting the mineral content, indicating an increased mineral turnover. Immunologic reactions may inhibit bone induction by DXBM, which can be counteracted by treatment with CsA.