Effects of long‐term cyclosporin therapy on the periodontium of rats

Background:  The treatment of cyclosporin A triggers an early bone loss and gingival overgrowth. There is a lack of studies exploring the effects of long‐term cyclosporin A therapy on alveolar bone homeostasis and gingival tissue. Objective:  The purpose of this study was to evaluate the effects of long‐term therapy with cyclosporin A on the gingival tissue and on the alveolar bone metabolism in rats. Materials and methods:  Rats were treated for 60, 120, 180 and 240 days with a daily subcutaneous injection of 10 mg/kg body weight of cyclosporin A. At the end of experimental periods, animals were killed and the serum calcium (Ca 2+ ) and alkaline phosphatase levels were measured in all groups. After histological processing, the oral epithelium and the connective tissue, as well as volume densities of alveolar bone ( V b ) and multinucleated osteoclasts ( V o ), were assessed at the region of the lower first molars. Results:  Significant increases in the serum alkaline phosphatase were observed in those groups that received cyclosporin A therapy. After 60 and 120 days of the treatment with cyclosporin A, evident gingival overgrowth associated with a significant increase of epithelium and connective tissue was observed, as well as a decrease of the densities of bone and an increase of densities of osteoclasts. After 180 and 240 days of the treatment, there was a reduction of the gingival overgrowth associated with significant decreases of epithelium and connective tissue, as well as an increase of bone densities and a decrease of osteoclasts. Conclusion:  Within the limits of this experimental study, it can be concluded that the deleterious periodontal effects of cyclosporin A administration may be time‐related side‐effects.