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重组人骨形态发生蛋白-2在胸腔镜辅助器械动物模型中增强前路脊柱融合。

Recombinant human bone morphogenetic protein-2 enhances anterior spinal fusion in a thoracoscopically instrumented animal model.

作者信息

Sucato Daniel J, Hedequist Daniel, Zhang Hong, Pierce William A, O'Brien Shana E, Welch Robert D

机构信息

Seay Center for Musculoskeletal Research, Texas Scottish Rite Hospital for Children, 2222 Welborn Street, Dallas, TX 75219, USA.

出版信息

J Bone Joint Surg Am. 2004 Apr;86(4):752-62. doi: 10.2106/00004623-200404000-00013.

DOI:10.2106/00004623-200404000-00013
PMID:15069140
Abstract

BACKGROUND

Thoracoscopically assisted anterior spinal arthrodesis and instrumentation is being used more widely to treat idiopathic scoliosis. However, harvesting autologous bone increases operative time and morbidity. The purpose of this study was to compare autologous iliac crest and rib graft with recombinant human bone morphogenetic protein-2 (rhBMP-2) in thoracoscopically assisted anterior spinal arthrodesis and instrumentation in an animal model.

METHODS

Twenty-two pigs underwent thoracoscopically assisted anterior spinal arthrodesis. Each animal had five contiguous thoracic discectomies followed by anterior instrumentation. The animals were randomly assigned to five treatment groups. Group I consisted of control animals that received no graft material; group II, animals treated with autologous rib graft; group III, animals treated with autologous iliac crest graft; group IV, animals treated with an rhBMP-2-composite sponge (collagen-hydroxyapatite-tricalcium phosphate carrier); and group V, animals treated with a composite sponge carrier alone. The animals were killed four months after the procedure, and the spines were harvested. The fusion mass was assessed with use of axial and sagittal computed tomography scans. The spines were tested biomechanically with incremental loads applied in the frontal and axial planes to achieve bending moments of up to 6.0 N-m. Angular motion at each segment was recorded with use of a three-dimensional motion analysis system. Histomorphometric analysis of each undecalcified disc segment was also performed.

RESULTS

The fusion grades, according to computed tomography analysis with use of a 4-point grading system in which scores of 3 and 4 indicated a solid fusion, were 0.6 point for group I, 2.1 points for group II, 2.3 points for group III, 3.8 points for group IV, and 0.4 point for group V. Group IV (the rhBMP-2-treated animals) had a higher grade than all of the other groups. Group II (rib graft) and group III (iliac crest) had similar grades, and both were greater than group I (the untreated controls) and group V (composite sponge alone) (p < 0.05). In axial rotation, lateral bending, and flexion-extension, the spines in group IV were stiffer than those in the four other groups (p < 0.05); the spines in groups II and III were similar, and the spines in both of those groups were stiffer than those in groups I and V (the control groups). Histologic analysis demonstrated that the total new-bone area, expressed as a percentage of the total disc space area, was 23.2% in group I, 37.1% in group II, 37.2% in group III, 48.5% in group IV, and 5.9% in group V. Group IV had significantly greater bone formation than all of the other groups (p < 0.001). The animals treated with rib graft (group II) and iliac crest (group III) had a similar amount of bone formation, and it was greater than that in both control groups (p < 0.001).

CONCLUSIONS

The rhBMP-2 significantly increased the prevalence and quality of the spinal fusion after thoracoscopically assisted anterior arthrodesis and instrumentation in an animal model compared with that in the other treatment groups and in the controls.

摘要

背景

胸腔镜辅助下前路脊柱融合内固定术在特发性脊柱侧凸的治疗中应用日益广泛。然而,自体骨取材会增加手术时间和并发症发生率。本研究旨在动物模型中比较自体髂嵴骨和肋骨植骨与重组人骨形态发生蛋白-2(rhBMP-2)在胸腔镜辅助下前路脊柱融合内固定术中的应用效果。

方法

22头猪接受胸腔镜辅助下前路脊柱融合术。每只动物均行连续5个胸椎椎间盘切除术,随后行前路内固定。动物被随机分为5个治疗组。I组为未接受植骨材料的对照动物;II组为接受自体肋骨植骨治疗的动物;III组为接受自体髂嵴骨植骨治疗的动物;IV组为接受rhBMP-2复合海绵(胶原-羟基磷灰石-磷酸三钙载体)治疗的动物;V组为仅接受复合海绵载体治疗的动物。术后4个月处死动物并取出脊柱。通过轴向和矢状面计算机断层扫描评估融合质量。在额状面和轴向面施加递增负荷以产生高达6.0 N·m的弯矩,对脊柱进行生物力学测试。使用三维运动分析系统记录每个节段的角度运动。还对每个未脱钙椎间盘节段进行了组织形态计量学分析。

结果

根据使用4分制的计算机断层扫描分析,3分和4分表示牢固融合,I组的融合评分为0.6分,II组为2.1分,III组为2.3分,IV组为3.8分,V组为0.4分。IV组(接受rhBMP-2治疗的动物)的评分高于所有其他组。II组(肋骨植骨)和III组(髂嵴骨植骨)评分相似,且均高于I组(未治疗的对照组)和V组(仅复合海绵)(p < 0.05)。在轴向旋转、侧方弯曲和屈伸时,IV组的脊柱比其他四组更僵硬(p < 0.05);II组和III组的脊柱相似,且这两组的脊柱比I组和V组(对照组)更僵硬。组织学分析表明,以椎间盘总间隙面积的百分比表示的新骨总面积,I组为23.2%,II组为37.1%,III组为37.2%,IV组为48.5%,V组为5.9%。IV组的骨形成明显多于所有其他组(p < 0.001)。接受肋骨植骨(II组)和髂嵴骨植骨(III组)治疗的动物骨形成量相似,且均多于两个对照组(p < 0.001)。

结论

与其他治疗组和对照组相比,在动物模型中,rhBMP-2显著提高了胸腔镜辅助下前路融合内固定术后脊柱融合的发生率和质量。

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