Are We at the End of the Bone Morphogenetic Protein Era? Commentary on an article by Diyar Delawi, MD, PhD, et al.: "OP-1 Compared with Iliac Crest Autograft in Instrumented Posterolateral Fusion. A Randomized, Multicenter Non-Inferiority Trial".
Are We at the End of the Bone Morphogenetic Protein Era? Commentary on an article by Diyar Delawi, MD, PhD, et al.: "OP-1 Compared with Iliac Crest Autograft in Instrumented Posterolateral Fusion. A Randomized, Multicenter Non-Inferiority Trial".
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我们正处于骨形态发生蛋白时代的末期吗？
DOI：
10.2106/jbjs.o.01198
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
J. Coe
中科院分区：
文献类型：
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作者：
J. Coe
一个多世纪以来，从偏远地区采集的自体骨移植物已被用于融合人类脊柱，以治疗疾病、退化或损伤1。世纪后半期，从髂嵴采集的自体骨是用于脊柱融合的“金标准”骨移植物。在接受自体髂嵴植骨（ICBG）脊柱融合术的患者中，有超过30%的患者报告了供体部位发病率，特别是持续一年以上的疼痛2。这种发病率导致许多研究人员寻找ICBG的替代品。研究开始集中在各种骨形态发生蛋白（BMP）的重组形式作为潜在的骨移植替代品。骨形态发生蛋白由马歇尔乌里斯特在20世纪60年代早期发现，是一个有点不均匀的蛋白质组的一个亚类，称为细胞因子，具有细胞信号传导作为一个共同特征。BMP被发现是骨诱导性的;也就是说，它们在骨形成中诱导成骨细胞活性。BMP，在其天然形式下，很难大量产生。开发了可以大量生产的重组形式，但生产成本高昂，需要工业界大量投资。这项投资似乎显示出成果，因为动物研究证明了BMP作为骨移植替代品的功效。这些研究随后进行了人体临床试验，其中两类BMP（重组人[rh] BMP-7和rhBMP-2）与ICBG相比，在实现脊柱骨关节炎方面表现出非劣效性。
Autologous bone graft harvested from remote locations has been used to fuse the human spine for the treatment of disease, degeneration, or injury for over a century1. For the latter half of the twentieth century, autologous bone harvested from the iliac crest was the “gold standard” bone graft used for spinal fusion. Donor-site morbidity, particularly pain lasting more than a year, has been reported in >30% of patients who have undergone spinal fusion with autologous iliac crest bone graft (ICBG)2. This morbidity led many investigators to search for alternatives to ICBG. Research began to focus on recombinant forms of a variety of bone morphogenetic proteins (BMPs) as a potential bone-graft substitute. BMPs, discovered by Marshall Urist in the early 1960s3, are a subclass of a somewhat inhomogeneous group of proteins known as cytokines that have cell signaling as a common feature. BMPs were found to be osteoinductive; that is, they induce osteoblastic activity in the formation of bone. BMPs, in their natural form, are very difficult to generate in quantity. Recombinant forms that could be produced in quantity were developed, but manufacturing them was expensive and required substantial investment by industry. This investment appeared to show fruit as animal studies demonstrated efficacy of BMPs as a bone-graft substitute. These studies were followed by human clinical trials, in which two classes of BMPs (recombinant human [rh] BMP-7 and rhBMP-2) demonstrated non-inferiority compared with ICBG for achieving spinal …