Effect of the long-term administration of Cyclosporine A on bone healing around osseointegrated titanium implants: A histomorphometric study in the rabbit tibia

The aim of this study was to investigate the effect of cyclosporine A (CsA) therapy on bone healing around osseointegrated implants in the rabbit by means of descriptive histologic and histomorphometric analyses. Eighteen rabbits received one implant each in the right tibia proximal metaphysis. After the bone-healing period of 3 months, 6 randomly selected animals were sacrificed (Group CTL-12) before the immunosuppression therapy initiation to obtain a standard of implant integration. Another six randomly selected animals were submitted to a daily subcutaneous (sc) injection of 10 mg/kg CsA (Group CsA) whereas the six remaining animals received daily sc injections of saline solution (Group CTL-24). Groups CTL-24 and CsA were sacrificed after another 12 weeks. Bone-to-implant contact (BIC), and bone area fraction occupancy (BAFO) within the implant threads were measured. Bone density (BD) and descriptive histological analyses were also accomplished. Rabbits under CsA therapy presented statistically lower percentage of BIC (33.28 +/- 6.19) compared to the animals of CLT-24 (55.6 +/- 17.73). No differences were found between CsA and CTL-12 (38.7 +/- 7.87). Significant decreased percentage of BAFO between the implant threads in the CsA (48.43 +/- 9.48) group compared to the CTL-24 (72.26 +/- 11.72) was observed. No differences were found between CsA and CTL-12 (61.99 +/- 13.94) groups. BD analysis showed significant lower BD in the CsA (48.56 +/- 9.32) group compared to the CTL-12 (68.74 +/- 10.89) and CTL-24 (77.96 +/- 4.96) groups. Collectively, our findings demonstrated that CsA therapy negatively affect the bone healing around osseointegrated implants due to the significant lower values for BIC, BAFO, and BD.