Effective Doses of Recombinant Human Bone Morphogenetic Protein‐2 in Experimental Spinal Fusion
Effective Doses of Recombinant Human Bone Morphogenetic Protein‐2 in Experimental Spinal Fusion
复制标题
重组人骨形态发生蛋白-2在实验性脊柱融合中的有效剂量
作者：
H. Sandhu;L. Kanim;J. Kabo;J. Toth;Erik N. Zeegen;David Liu;R. Delamarter;E. Dawson
研究设计19只狗接受了L4-L5横突间融合，其中58μg、115μg、230μg、460μg或920μg重组人骨形态发生蛋白-2由聚乳酸聚合物携带。先前的一项研究(12只狗)在该模型中比较了2300μg重组人骨形态发生蛋白-2、自体髂骨和单独载体。随后对所有的融合进行了比较。目的研究重组人骨形成蛋白-2在脊柱融合模型中的量效关系。背景资料概述重组骨诱导因子，如重组人骨形态发生蛋白-2，在脊椎骨骨干缺损和脊柱融合模型中是有效的。假设在阈值剂量以上，重组人骨形态发生蛋白-2所产生的脊柱融合的质量不会随着诱导蛋白的增加而改变。方法后牙去皮质后，沿双侧横突间隙植入指定种植体。3个月后通过计算机断层扫描、高分辨率X线片、手动测试、机械测试和组织学分析对融合部位进行评估。结果与使用2300μg重组人骨形成蛋白-2的研究一样，植入58-920μg的重组人骨形成蛋白-2成功地使犬3个月的横突间融合。这并不只发生在含有自体移植物或携带者的动物身上。L4-L5椎间融合块横截面积和机械刚度不呈剂量依赖性。组织学结果各不相同，但与rhBMP-2的剂量无关。对复合种植体的炎症反应与融合块的体积成反比。结论重组人骨形态发生蛋白-2剂量变化40倍，在横突间融合的质量上没有机械、放射学或组织学上的差异。
Study Design Nineteen dogs underwent L4‐L5 intertransverse process fusions with either 58 μg, 115 μg, 230 μg, 460 μg, or 920 μg of recombinant human bone morphogenetic protein‐2 carried by a polylactic acid polymer. A previous study (12 dogs) compared 2300 μg of recombinant human bone morphogenetic protein‐2, autogenous iliac bone, and carrier alone in this model. All fusions subsequently were compared. Objectives To characterize the dose‐response relationship of recombinant human bone morphogenetic protein‐2 in a spinal fusion model. Summary of Background Data Recombinant osteoinductive morphogens, such as recombinant human bone morphogenetic protein‐2, are effective in vertebrate diaphyseal defect and spinal fusion models. It is hypothesized that the quality of spinal fusion produced with recombinant human bone morphogenetic protein‐2, above a threshold dose, does not change with increasing amounts of inductive protein. Methods After decortication of the posterior elements, the designated implants were placed along the intertransverse process space bilaterally. The fusion sites were evaluated after 3 months by computed tomography imaging, high‐resolution radiography, manual testing, mechanical testing, and histologic analysis. Results As in the study using 2300 μg of recombinant human bone morphogenetic protein‐2, implantation of 58–920 μg of recombinant human bone morphogenetic protein‐2 successfully resulted in intertransverse process fusion in the dog by 3 months. This had not occurred in animals containing autograft or carrier alone. The cross‐sectional area of the fusion mass and mechanical stiffness of the L4‐L5 intersegment were not dose‐dependent. Histologic findings varied but were not related to rhBMP‐2 dose. Inflammatory reaction to the composite implant was proportional inversely to the volume of the fusion mass. Conclusions No mechanical, radiographic, or histologic differences in the quality of intertransverse process fusion resulted from a 40‐fold variation in dose of recombinant human bone morphogenetic protein‐2.