The effects of cyclosporin A on bone turnover and repair

Abstract: The effects of cyclosporin A on bone metabolism are unclear and controversial. The aims of this thesis were to study the effects of cyclosporin A on bone turnover and on different repair processes such as fracture healing, osteoinduction and osteoconduction.Osteoinduction was studied by implanting inductive demineralized bone matrix in the abdominal muscles of rats. Matrix from different species (rat and rabbit) was used, and the amount of bone formation, the degree of matrix resorption, the occurrence of neuropeptide containing nerve endings, and calcium incorporation were studied. Cyclosporin A was found to enhance bone induction in allogeneic and xenogeneic bone matrix, while resorption of the demineralized bone matrix was unaffected. The mineral turnover in the induced ossicles was not affected by cyclosporin A treatment. Cyclosporin A treatmentresulted in the normal occurrence of neuropeptide containing nerve endings in xenografts.Bone ingrowth into allografts and xenografts was studied in the rat using bone chambers. At 6 weeks there was less bone ingrowth into the xenografts than into the allografts. This difference was unaffected by cyclosporin A treatment.In the intact skeleton in growing rats, cyclosporin A treatment induced an early transient increase in mineral and matrix turnover, but the total mineral content was unaffected. Tibia fractures were created in rabbits. Cyclosporin A treatment increased callus volume and bone mineral content in the fractured tibia as compared to controls. Disuse osteopenia in the femora was unaffected by cyclosporin A.In conclusion, cyclosporin A enhanced osteoinduction in rats, but it did not affect osteoconduction. Furthermore, cyclosporin A induced increased bone turnover in intact bone without affecting the total mineral content Bone mineral content and callus volume in rabbit tibia fractures were increased by cyclosporin A. The mechanism for the stimulation of bone formation is unclear, but a direct or cytokine mediated effect on bone forming cells is possible.