Boden S D, Schimandle J H, Hutton W C
Department of Orthopaedics, Emory University School of Medicine, Decatur, Georgia, USA.
Spine (Phila Pa 1976). 1995 Dec 15;20(24):2633-44. doi: 10.1097/00007632-199512150-00004.
Efficacy of a bovine-derived osteoinductive growth factor was studied in a rabbit model and in a nonhuman primate model of posterolateral lumbar spinal fusion.
To determine the minimum effective dose of growth factor and the influence of different carrier material on the outcome of intertransverse process lumbar fusion.
Bone morphogenetic proteins and related growth factors are becoming increasingly available in purified extract or genetically engineered forms and are capable of inducing new bone formation in vivo. Osteoinductive growth factors to enhance lumbar spinal infusion have not been well studied in models of posterolateral intertransverse process fusion. Because of the diminished potential of bone regeneration in primates (including humans) compared with phylogenetically lower animals, extrapolations regarding dose and efficacy cannot be made directly from results obtained in experiments performed on phylogenetically lower animals. Experiments on non-human primates are a critical step before attempting to use these growth factors on humans. METHODS. One hundred fifteen adult New Zealand white rabbits and 10 adult rhesus macaques underwent single level posterolateral intertransverse process lumbar spinal arthrodesis to evaluate different doses and carrier materials for a bovine-derived osteoinductive bone protein extract. Rabbit fusion masses were evaluated 5 weeks after arthrodesis by manual palpation, radiography, biomechanical testing, and light microscopy. Monkey fusion masses were evaluated 12 weeks after arthrodesis by radiography and light microscopy.
Successful posterolateral intertransverse process spinal fusions were achieved in the rabbit models using an osteoinductive growth factor with three different carriers (autogenous iliac bone, demineralized allogeneic bone matrix, and natural coral). There was a dose-dependent response to the osteoinductive growth factor in the rabbit model, indicating that a threshold must be overcome before bone formation is induced. The methodology for biologic enhancement of spinal fusion developed in the rabbit model transferred successfully to the rhesus monkey, where the use of the osteoinductive growth factor with a demineralized bone matrix carrier resulted in spinal fusion in 12 weeks.
These experiments provide an essential building block in the understanding of the biology of spinal fusion and the use of osteoinductive growth factors to enhance a posterolateral intertransverse process spinal fusion. The achievement of posterolateral spinal fusion in the rhesus monkey using an osteoinductive growth factor is a significant step toward the biologic enhancement of spinal fusion in humans.
在兔模型和腰椎后外侧融合的非人灵长类动物模型中研究了一种牛源骨诱导生长因子的疗效。
确定生长因子的最小有效剂量以及不同载体材料对横突间腰椎融合结果的影响。
骨形态发生蛋白及相关生长因子越来越多地以纯化提取物或基因工程形式获得，并且能够在体内诱导新骨形成。在腰椎后外侧横突间融合模型中，用于增强腰椎融合的骨诱导生长因子尚未得到充分研究。由于与进化程度较低的动物相比，灵长类动物（包括人类）的骨再生潜力降低，因此不能直接从进化程度较低的动物实验结果推断剂量和疗效。在尝试将这些生长因子应用于人类之前，对非人灵长类动物进行实验是关键的一步。方法：115只成年新西兰白兔和10只成年恒河猴接受了单节段腰椎后外侧横突间脊柱融合术，以评估牛源骨诱导骨蛋白提取物的不同剂量和载体材料。兔融合块在融合术后5周通过手动触诊、X线摄影、生物力学测试和光学显微镜进行评估。猴融合块在融合术后12周通过X线摄影和光学显微镜进行评估。
在兔模型中，使用骨诱导生长因子与三种不同载体（自体髂骨、脱矿同种异体骨基质和天然珊瑚）成功实现了腰椎后外侧横突间脊柱融合。在兔模型中，对骨诱导生长因子存在剂量依赖性反应，表明在诱导骨形成之前必须克服一个阈值。在兔模型中开发的脊柱融合生物增强方法成功转移到恒河猴身上，在恒河猴中，使用脱矿骨基质载体的骨诱导生长因子在12周内实现了脊柱融合。
这些实验为理解脊柱融合生物学以及使用骨诱导生长因子增强腰椎后外侧横突间脊柱融合提供了重要的基础。使用骨诱导生长因子在恒河猴中实现腰椎后外侧脊柱融合是朝着人类脊柱融合生物增强迈出的重要一步。
