AIMS To develop an early implant instability murine model and explore the use of intermittent parathyroid hormone (iPTH) treatment for initially unstable implants. METHODS 3D-printed titanium implants were inserted into an oversized drill-hole in the tibiae of C57Bl/6 mice (n = 54). After implantation, the mice were randomly divided into three treatment groups (phosphate buffered saline (PBS)-control, iPTH, and delayed iPTH). Radiological analysis, micro-CT (µCT), and biomechanical pull-out testing were performed to assess implant loosening, bone formation, and osseointegration. Peri-implant tissue formation and cellular composition were evaluated by histology. RESULTS iPTH reduced radiological signs of loosening and led to an increase in peri-implant bone formation over the course of four weeks (timepoints: one week, two weeks, and four weeks). Observational histological analysis shows that iPTH prohibits the progression of fibrosis. Delaying iPTH treatment until after onset of peri-implant fibrosis still resulted in enhanced osseointegration and implant stability. Despite initial instability, iPTH increased the mean pull-out strength of the implant from 8.41 N (SD 8.15) in the PBS-control group to 21.49 N (SD 10.45) and 23.68 N (SD 8.99) in the immediate and delayed iPTH groups, respectively. Immediate and delayed iPTH increased mean peri-implant bone volume fraction (BV/TV) to 0.46 (SD 0.07) and 0.34 (SD 0.10), respectively, compared to PBS-control mean BV/TV of 0.23 (SD 0.03) (PBS-control vs immediate iPTH, p < 0.001; PBS-control vs delayed iPTH, p = 0.048; immediate iPTH vs delayed iPTH, p = 0.111). CONCLUSION iPTH treatment mediated successful osseointegration and increased bone mechanical strength, despite initial implant instability. Clinically, this suggests that initially unstable implants may be osseointegrated with iPTH treatment. Cite this article: Bone Joint Res 2022;11(5):260-269.

中文翻译：

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间歇性甲状旁腺激素可增加稳定性并改善最初不稳定的植入物的骨整合。

目的 开发早期种植体不稳定性小鼠模型，并探索使用间歇性甲状旁腺激素 (iPTH) 治疗最初不稳定的种植体。方法 将 3D 打印的钛植入物插入 C57Bl/6 小鼠 (n = 54) 胫骨的超大钻孔中。植入后，小鼠被随机分为三个治疗组（磷酸盐缓冲盐水 (PBS)-对照、iPTH 和延迟 iPTH）。进行了放射学分析、显微 CT (µCT) 和生物力学拔出测试，以评估植入物松动、骨形成和骨整合。通过组织学评估种植体周围组织形成和细胞组成。结果 iPTH 减少了松动的放射学迹象，并导致种植体周围骨形成在 4 周内增加（时间点：1 周、2 周和 4 周）。观察组织学分析显示 iPTH 阻止纤维化的进展。将 iPTH 治疗延迟到种植体周围纤维化发生后仍然会导致骨整合和种植体稳定性增强。尽管初始不稳定，但 iPTH 将植入物的平均拔出强度从 PBS 对照组的 8.41 N (SD 8.15) 增加到立即和延迟 iPTH 组的 21.49 N (SD 10.45) 和 23.68 N (SD 8.99)，分别。与 PBS 对照平均 BV/TV 0.23 (SD 0.03) (PBS-对照与即时 iPTH，p < 0.001；PBS 对照与延迟 iPTH，p = 0.048；即时 iPTH 与延迟 iPTH，p = 0.111）。结论 iPTH 治疗介导了成功的骨整合并增加了骨机械强度，尽管初始种植体不稳定。在临床上，这表明最初不稳定的植入物可能通过 iPTH 治疗实现骨整合。引用这篇文章：Bone Joint Res 2022;11(5):260-269。