The use of an osteoinductive growth factor for lumbar spinal fusion .2. Study of dose, carrier, and species
The use of an osteoinductive growth factor for lumbar spinal fusion .2. Study of dose, carrier, and species
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DOI：
10.1097/00007632-199512150-00004
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发表时间：
1995-12-15
期刊：
影响因子：
3
通讯作者：
Hutton, WC
中科院分区：
文献类型：
--
作者：
Boden, SD;Schimandle, JH;Hutton, WC
研究设计。研究了牛源性骨诱导生长因子在兔模型和非人灵长类动物腰椎后外侧融合术中的有效性。目的：确定生长因子的最小有效剂量以及不同载体材料对腰椎横突间融合术结果的影响。骨形态发生蛋白和相关生长因子正变得越来越多地以纯化提取物或基因工程形式提供，并能够在体内诱导新骨形成。骨诱导生长因子促进腰椎融合尚未在后外侧横突间融合模型中得到很好的研究。由于与系统发育较低的动物相比，灵长类动物(包括人类)的骨再生潜力较小，因此不能直接根据对系统发育较低的动物进行的实验结果来推断剂量和疗效。在非人类灵长类动物身上进行实验是尝试在人类身上使用这些生长因子之前的关键一步。115只成年新西兰白兔和10只成年恒河猴进行单节段后外侧横突间关节融合术，以评价不同剂量和载体材料的牛源性骨诱导性骨蛋白提取物，关节融合术后5周对兔融合块进行人工触诊、放射学、生物力学测试和光学显微镜观察。术后12周行X线片和光镜检查，观察融合肿块的形态。在兔模型中，使用骨诱导生长因子和三种不同的载体(自体髂骨、脱钙同种异体骨基质和天然珊瑚)成功地实现了后外侧横突间脊柱融合。在兔模型中，对骨诱导生长因子有剂量依赖性的反应，这表明在诱导骨形成之前必须克服一个阈值。在兔模型中建立的生物增强脊柱融合的方法学被成功地移植到恒河猴身上，在12周内使用骨诱导生长因子和脱钙骨基质载体进行脊柱融合。这些实验为理解脊柱融合的生物学和使用骨诱导生长因子加强后外侧横突间脊柱融合提供了必要的基础。使用骨诱导生长因子实现恒河猴脊柱后外侧融合是人类脊柱融合生物强化的重要一步。
Study Design. 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.Objectives. To determine the minimum effective dose of growth factor and the Influence of different carrier material on the outcome of intertransverse process lumbar fusion.Summary of Background Data. 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 fusion 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 nonhuman primates are a critical step before attempting to use these growth factors in 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 fora 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.Results. Successful posterolateral intertransverse process spinal fusions were achieved in the rabbit model 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 was 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.Conclusions. 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.