Trauma Center, National Institute of Traumatology and Orthopedics, Rio de Janeiro 20940-070, Brazil.
Research Division, National Institute of Traumatology and Orthopedics, Rio de Janeiro 20940-070, Brazil.
Injury. 2021 Jul;52 Suppl 3:S3-S12. doi: 10.1016/j.injury.2021.03.063. Epub 2021 Jun 1.
The treatment of large segmental defects of long bones resulting from trauma, infection, or bone tumor resections is a major challenge for orthopedic surgeons. The reconstruction of bone defects with acellular allografts can be used as an osteoconductive approach. However, devitalized allografts are associated with high rates of clinical failure as a result of poor intrinsic osteoinduction properties and a lack of further remodeling. Nevertheless, evidence suggests that due to its anabolic properties, teriparatide (PTH) could be effective as an adjuvant therapy for massive allograft healing. Therefore, our goal was to investigate in a murine critical-sized defect model whether the intermittent administration of PTH improves the incorporation and revitalization of acellular structural bone allografts. Thus, a 2.5-mm critical-sized defect was established in the right femur of C57BL/6 mice, followed by the reconstruction with a devitalized cortical structural allograft. A titanium micro locking plate was applied to the anterior femoral surface and secured in place with self-tapping locking screws. Subsequently, daily doses of PTH (30, and 40 µg/kg) or saline were administered to the mice for 14 days after surgery. The mice were maintained without PTH therapy for an additional 7 days before being euthanized at 3 weeks post-surgery. Bone graft consolidation was assessed on radiographic images and by histomorphometric analysis. Additionally, to determine the frequency of osteoprogenitor cells in the bone marrow and their in vitro osteogenic capacity, stromal cells were isolated from the bone marrow of animals treated with 30 or 40 µg/kg/day of PTH following the same protocol used for the experimental animals. Our results suggest that intermittent PTH treatment at 30 µg/kg/day after femoral allograft reconstruction surgery accelerated the healing process as evidenced by new bone formation induced on endosteal and periosteal surfaces, enhanced revitalization of allogeneic graft, and increased frequency and osteogenic capacity of bone marrow stromal cells (BMSC). These findings should encourage further studies aimed at investigating the potential therapeutic use of intermittent PTH, specifically with regards to the optimal dosing regimen in clinically challenging orthopedic scenarios.
创伤、感染或骨肿瘤切除导致的大段骨缺损的治疗是骨科医生面临的主要挑战。使用脱细胞同种异体移植物进行骨缺损重建可用作骨诱导方法。然而，由于缺乏内在的成骨诱导特性和缺乏进一步的重塑，失活的同种异体移植物的临床失败率很高。尽管如此，有证据表明，由于其合成代谢特性，特立帕肽（PTH）可能作为同种异体移植物大量愈合的辅助治疗有效。因此，我们的目标是在鼠临界尺寸缺陷模型中研究 PTH 的间歇性给药是否改善脱细胞结构性骨同种异体移植物的结合和复活。因此，在 C57BL/6 小鼠的右侧股骨中建立了 2.5 毫米的临界尺寸缺陷，随后用失活的皮质结构性同种异体移植物进行重建。钛微锁定板应用于股骨前表面，并使用自攻锁定螺钉固定到位。随后，在手术后每天向小鼠给予 PTH（30 和 40μg/kg）或盐水，持续 14 天。在手术后 3 周处死小鼠之前，将小鼠维持无 PTH 治疗另外 7 天。通过放射图像和组织形态计量分析评估移植物的骨整合。此外，为了确定骨髓中的成骨前体细胞的频率及其体外成骨能力，按照与实验动物相同的方案，从接受每天 30 或 40μg/kg PTH 治疗的动物的骨髓中分离基质细胞。我们的结果表明，在股骨同种异体移植物重建手术后每天以 30μg/kg 的剂量间歇性给予 PTH 可加速愈合过程，这表现为在内侧和骨膜表面诱导新骨形成，增强同种异体移植物的复活，并增加骨髓基质细胞（BMSC）的频率和成骨能力。这些发现应该鼓励进一步研究，旨在研究间歇性 PTH 的潜在治疗用途，特别是在临床挑战性的骨科情况下的最佳剂量方案。
