Effects of low-dose cyclosporin on osteogenesis of human demineralized bone grafts in a surgically created mandibular defect in rats

Background: Demineralized freeze-dried bone matrix (DFDBM) stimulates new bone formation; however, immune reactions from the residual antigens of prepared grafts might play a role in inducing osteogenesis. This study examined whether cyclosporine-A (CsA), an immunosuppressant, enhanced the DFDBM-induced new bone formation. Methods: After creating a bony defect in the posterior mandible, 40 male Sprague-Dawley rats were divided into four groups of 10 each: no graft with mineral oil (control); no graft with CsA in mineral oil; DFDBM with mineral oil; and DFDBM with CsA in mineral oil (combined therapy). CsA was administered at 2 mg/kg body weight. Five rats in each group were sacrificed at days 10 and 28 and tissue samples were taken for histological examination. Results: Soft tissue was observed in the defects of all animals without grafts, whereas the repaired hard tissue formed in the defects of animals with grafts. Histometery, which was performed only at day 10, revealed both DFDBM and CsA therapies produced a significant increase in the total area of repaired hard tissue. Only CsA therapy significantly increased the new bone area. Compared with the DFDBM group, the composition of the repaired hard tissue in the combined therapy group shifted; i.e., the new bone area increased but the residual particle area decreased. The cartilage formation was greater in the combined therapy group than the DFDBM group. Conclusion: Within the limitations of this study, we suggest that the DFDBM grafts play a major role, which could be enhanced by CsA, in the induction of new bone formation, especially at an early phase.