Treatment with cyclosporine attenuates the inflammatory process and severity of bisphosphonate-induced osteonecrosis of the jaws in rats.

INTRODUCTION

Osteonecrosis usually occurs with necrotic bone exposure in the mandible asymptomatically for long periods but can evolve to present pain, fistula, odor, bleeding, and suppuration.

OBJECTIVE

To evaluate the influence of cyclosporine treatment and its influence on osteonecrosis in a rat model.

METHODS

The animals were randomly divided into 05 groups (n = 8/group). The negative control group (SAL), positive control group treated with zoledronic acid (ZA + SAL), and test groups were treated with cyclosporine A (CsA) at 5, 2.5, and 1.25 mg/kg and treated with ZA. The left lower second molars were extracted. The animals were euthanized 1 month after tooth extraction. Digital radiographs, histological slides, and immunoexpression of IL-2, IL-6, TNF-α, PPAR-γ, c-Fos, c-Jun, FoxP3, and INF-γ were analyzed. Western blot assays were performed to investigate the expression of RORyT. In addition, hematological analysis, body mass variation, and femur mechanical tests were performed.

RESULTS

Radiographs showed that in the groups treated with ZA, there was an increase in the radiolucent area suggestive of osteonecrosis, and treatment with cyclosporine did not reduce this parameter (p < 0.001). In the western blot analysis, animals treated with ZA showed increased expression of RORyT (1.887 ± 0.114) compared to the saline group (0.799 ± 0.107), and treatment with the highest dose of cyclosporine (0.652 ± 0.070) reduced this expression (p < 0.001).

DISCUSSION: Studies have observed bone health in animals treated with CsA. Treatment with this immunosuppressant showed a bone-protective effect of CsA, which corroborates our findings.

CONCLUSION

Treatment with CsA reduced the immunoexpression of pro-inflammatory cytokines such as IL-2 and TNF-α and decreased the expression of RORyT.