Cyclosporin A Enhances Callus Formation in Rabbit Tibia Fractures

Purpose: Drugs that modify the production of cytokines may affect fracture healing. The immunosuppressive drug cyclosporin A is widely used to modify the immune response in transplantations and in treatment of rheumatoid disorders. We wanted to analyze the effect of cyclosporin A on fracture healing and on the development of trauma induced osteopenia. Methods: Experimental tibia fractures were stabilised with intramedullary pins in 26 rabbits. The animals were given 5 mg/kg/day of cyclosporin A or placebo for 5 weeks. Bone mineral content, callus volume and biomechanical testing were performed on both tibias and femurs. Results: At 5 weeks cyclosporin A treatment resulted in increased bone mineral content and increased callus volume of the fractured bone. The femora on the operated side had significantly lower bone mineral content compared to the non-operated side. This trauma induced osteopenia was unaffected by cyclosporin A treatment. Failure torque and stiffness of the tibia and femora were similar in both groups. Interpretation: Cyclosporin A stimulates bone formation in fracture repair. The mechanism is unclear, but a direct or cytokine mediated effect on bone forming cells, or enhanced bone induction resulting in increased bone formation, is possible.