Department of Neurosurgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Department of Neurosurgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
World Neurosurg. 2018 Jul;115:e366-e374. doi: 10.1016/j.wneu.2018.04.058. Epub 2018 Apr 17.
Parathyroid hormone (PTH) (1-34) treatment reduces fracture risk in osteoporotic patients. Previously, we demonstrated in a rabbit model that low-dose PTH treatment resulted in increased fusion mass volume. As effects of PTH on bone are dose-dependent, we aimed to evaluate whether increasing dosage of PTH increases both volume and biomechanical stiffness of the resulting fusion masses and/or exhibits synergistic effects with low-dose bone morphogenetic protein 2 (BMP-2).
Posterolateral lumbar spinal fusion surgery was performed on 60 New Zealand White rabbits divided into 6 experimental groups: iliac crest autograft alone, autograft plus 20 μg/kg/day PTH, autograft plus 40 μg/kg/day PTH, BMP-2 alone, BMP-2 plus 20 μg/kg/day PTH, and BMP-2 plus 40 μg/kg PTH. Fusion was assessed at postoperative week 6 via manual palpation, volumetric computed tomography analysis, and 4-point bending biomechanical testing.
All groups treated with BMP-2 fused. Increasing doses of PTH resulted in increased fusion mass volume compared with autograft alone. Autograft plus 40 μg/kg/day PTH yielded fusion mass volumes comparable to BMP-2. When the autograft groups were considered alone, increased mechanical stiffness was observed only in the 20 μg/kg/day group. No significant stiffness differences were observed between BMP-2 groups.
Treatment with the highest dose of PTH resulted in fusion mass volumes similar to those obtained with BMP-2. When the autograft groups were considered alone, significant increases in mechanical stiffness were observed at a dosage of 20 μg/kg/day, suggesting there may be an optimal dose of PTH in the rabbit model. Effects of BMP-2 on fusion were dominant.
甲状旁腺激素(PTH)(1-34)治疗可降低骨质疏松患者的骨折风险。此前,我们在兔模型中证明,低剂量 PTH 治疗可增加融合质量体积。由于 PTH 对骨骼的作用呈剂量依赖性,我们旨在评估增加 PTH 剂量是否会增加融合质量的体积和生物力学刚度,和/或与低剂量骨形态发生蛋白 2(BMP-2)表现出协同作用。
对 60 只新西兰白兔进行后路腰椎融合手术,分为 6 个实验组:髂嵴自体移植物单独,自体移植物加 20 μg/kg/天 PTH,自体移植物加 40 μg/kg/天 PTH,BMP-2 单独,BMP-2 加 20 μg/kg/天 PTH 和 BMP-2 加 40 μg/kg PTH。术后第 6 周通过手动触诊、体积计算机断层扫描分析和 4 点弯曲生物力学测试评估融合。
所有接受 BMP-2 治疗的组均融合。与单独自体移植物相比,增加 PTH 剂量可增加融合质量体积。自体移植物加 40 μg/kg/天 PTH 产生的融合质量体积与 BMP-2 相当。当仅考虑自体移植物组时,仅在 20 μg/kg/天组观察到机械刚度增加。BMP-2 组之间未观察到明显的刚度差异。
用最高剂量的 PTH 治疗可获得与 BMP-2 相似的融合质量体积。当仅考虑自体移植物组时,在 20 μg/kg/天的剂量下观察到机械刚度显著增加,表明在兔模型中可能存在 PTH 的最佳剂量。BMP-2 对融合的影响占主导地位。