Department of Orthopedic Surgery, Rush University, Chicago, IL 60612, USA.
Spine (Phila Pa 1976). 2011 Feb 1;36(3):192-6. doi: 10.1097/BRS.0b013e3181cdd396.
Prospective randomized controlled animal model.
The purpose of this study is to determine whether the readministration of human recombinant bone morphogenetic protein-2 (rhBMP-2) induces an immune response and inhibits successful fusion in repeat posterolateral spinal surgery.
Little research has been performed on the effectiveness or immunoreactivity of rhBMP-2 (Infuse, Medtronic, Memphis, TN) in the context of its reuse in posterolateral fusion spinal surgery at adjacent levels.
A total of 34 New Zealand White rabbits underwent posterior intertransverse process fusion with the use of rhBMP-2 delivered on an absorbable collagen sponge (rhBMP-2/ACS). Two rabbits were killed early leaving 32 total rabbits. Serologic studies (Type I bovine collagen and rhBMP-2 antibodies) were obtained at 2-week intervals throughout the experiment. At 10 weeks, posteroanterior radiographs confirmed solid fusion masses in all rabbits. The 32 rabbits were randomly separated into 2 groups of 16, and each group underwent an adjacent level, bilateral intertransverse process fusion with either rhBMP-2/ACS or iliac crest.
There was no statistical difference in fusion rates with repeat use of rhBMP-2 (n = 15/16, 94%) or iliac crest (n = 11/16, 69%) (P = 0.17) at the adjacent level. Four rabbits (n = 4/32, 13%) developed rhBMP-2 antibodies. Of these 4 rabbits, 1 developed anti-rhBMP antibodies after the first exposure and 3 developed antibodies after the second surgery. Eight rabbits (n = 8/32, 25%) developed collagen antibodies with 7 rabbits developing antibodies after the first exposure and 1 rabbit developing antibodies after the second exposure. The development of antibodies did not effect fusion rates. No rabbit demonstrated evidence of a systemic or anaphylactic reaction to repeat exposure to rhBMP-2.
rhBMP-2 appears to be successful in promoting intertransverse fusions when used in both primary and repeat fusion environments. The infrequent development of antibodies to rhBMP-2 after re-exposure occurs without a predictable time course suggesting that host immunologic variation may play a role. This animal study would tend to support early clinical data emerging on the reuse of BMP-2 for lumbar fusion, suggesting an acceptable fusion rate without a high incidence of complications.
前瞻性随机对照动物模型。
本研究旨在确定在重复后路脊柱手术中重新给予人重组骨形态发生蛋白-2（rhBMP-2）是否会引起免疫反应并抑制成功融合。
在后路融合脊柱手术中将 rhBMP-2（Infuse，Medtronic，Memphis，TN）重复使用的有效性或免疫反应性方面，研究甚少。
34 只新西兰白兔接受后路横突间融合术，使用 rhBMP-2 与可吸收胶原海绵（rhBMP-2/ACS）联合使用。2 只兔子在早期死亡，共有 32 只兔子存活。整个实验过程中，每隔 2 周进行一次血清学研究（I 型牛胶原蛋白和 rhBMP-2 抗体）。10 周后，前后位 X 线片证实所有兔子均有坚固的融合肿块。32 只兔子随机分为 2 组，每组 16 只，每组均在相邻水平进行双侧横突间融合，使用 rhBMP-2/ACS 或髂嵴。
重复使用 rhBMP-2（n = 15/16，94%）或髂嵴（n = 11/16，69%）的融合率无统计学差异（P = 0.17）。4 只兔子（n = 4/32，13%）产生 rhBMP-2 抗体。其中 1 只兔子在首次暴露后产生抗 rhBMP 抗体，3 只兔子在第二次手术后产生抗体。8 只兔子（n = 8/32，25%）产生胶原蛋白抗体，7 只兔子在首次暴露后产生抗体，1 只兔子在第二次暴露后产生抗体。抗体的产生并不影响融合率。没有兔子对重复接触 rhBMP-2 表现出全身或过敏反应的证据。
rhBMP-2 在初次融合和重复融合环境中均能成功促进横突间融合。在再次暴露后，rhBMP-2 抗体的偶发发展发生而没有可预测的时间过程，这表明宿主免疫变异可能起作用。这项动物研究倾向于支持早期临床数据对 BMP-2 用于腰椎融合的再利用，表明接受率高而无并发症发生率高。
