Teriparatide mitigates peri-implant tibial bone deterioration in a post-irradiation tibial implantation model by restoring anabolic signaling

Background Radiation-associated impairment of bone quality is a major challenge in implant-bearing bone and may contribute to later aseptic failure. Whether teriparatide can mitigate peri-implant skeletal deterioration in a post-irradiation implantation setting remains incompletely defined. Methods A post-irradiation tibial implantation model was established, in which local irradiation was delivered before tibial implant placement. Animals were assigned to three groups: Implant, Implant + RT, and Implant + RT + TPTD, and teriparatide was administered subcutaneously after surgery. Peri-implant tibial bone changes were evaluated by micro-computed tomography. To assess osteoclastogenesis, RAW264.7 macrophages were cultured with RANKL in the presence or absence of 10 nM teriparatide. Subsequent evaluations were conducted utilizing tartrate-resistant acid phosphatase (TRAP) assays, immunoblotting, and qRT-PCR. In vivo bone tissues were further analyzed for bone remodeling-, osteogenesis-, Wnt-related, and damage-associated markers by western blotting and quantitative real-time PCR. Results In the post-irradiation tibial implantation model, irradiation markedly degraded peri-implant trabecular bone structure, as indicated by lower BMD, BV/TV, and Tb.N, together with higher Tb.Sp. Teriparatide partially reversed these structural changes. In the in vitro setting, teriparatide hindered osteoclast formation and downregulated the levels of NFATc1, CTSK, c-Fos, and TRAP. In vivo, teriparatide restored bone remodeling balance, as indicated by an increased OPG/RANKL ratio, and upregulated osteogenic markers including RUNX2 and OCN. Mechanistically, teriparatide restored β-catenin signaling, reduced SOST expression, and attenuated γH2AX and cleaved caspase-3 levels in irradiated bone. Conclusion Teriparatide mitigates peri-implant tibial bone deterioration in a post-irradiation implantation model and is accompanied by suppression of osteoclastogenic programming, restoration of bone remodeling balance, reactivation of anabolic signaling, and reduction of radiation-related damage. These findings support teriparatide as a potential early intervention strategy for alleviating radiation-associated skeletal vulnerability during early osseointegration in previously irradiated implant-bearing bone, rather than as a treatment for established long-term implant loosening.