Blocking Osteoclastogenesis With Zoledronate or Interferon-γ Enhances Bone Graft Efficacy

Objectives: Severe osteolysis and inflammatory responses always result in the failure of bone graft implantation in periodontics and implantology, and there are still no effective therapies to interfere with this disease process. The objective of this study was to find the mechanism underlying osteolysis and whether Zoledronate or IFN-γ can enhance the efficacy of bone graft for bone regeneration.
Methods: A total of 64 male Sprague-Dawley rats were used for the transplantation. Criticize bone defect was created at the center of the skull. Six experimental groups were established: alpha-tricalcium phosphate/collagen sponge (ɑ-TCP/CS), autogenous bone, α-TCP/CS with IFN-γ injection, α-TCP/CS with Zoledronate injection, autogenous bone with IFN-γ injection, and α-TCP/CS with IFN-γ injection. The rat skull samples were analyzed using RT-PCR, micro-CT, immunostaining, and histomorphometry.
Results: 1. Bone volume of the IFN-γ injection group increased to 80.8 ± 6.99% (for autogenous bone filling) and 64.6 ± 10.32% (for the ɑ-TCP/CS group); bone volume of the Zoledronate injection group increased to 78.25 ± 5.73 and 74.75 ± 9.70, compared to 19.975 ± 6.59% and 47.2% ± 8.16%, respectively (p < 0.05) for the control group 2. Immunostaining showed that the area of TNF-α and RANKL-positive fibrotic tissue in 8 weeks were significantly reduced in both IFN-γ and Zoledronate group, compared with no treatment group (p < 0.05). 3. TRAP staining showed that after Zoledronate and IFN-γ injections, osteoclasts dropped to 12.7% and 27.6%, respectively, (p < 0.05) in the autogenous bone group and 31.8% and 13.3%, respectively, in the α-TCP/CS group (p < 0.05).
Conclusions: (1) Severe osteoclastogenesis induced by overexpression of TNF-ɑ and RANKL causes serious bone degradation (2) Blocking osteoclastogenesis using IFN-γor Zoledronate can diminish bone resorption and enhance the efficacy of the bone graft.