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在比格犬后路腰椎模型中比较激活素 A/BMP-2 嵌合体(AB204)和 rhBMP-2 的成骨和融合率。

Comparison of the osteogenesis and fusion rates between activin A/BMP-2 chimera (AB204) and rhBMP-2 in a beagle's posterolateral lumbar spine model.

机构信息

Department of Orthopedic Surgery, Seoul National University, College of Medicine, SMG-SNU Boramae Medical Center, Boramae-ro 5-gil 20, Dongjak-gu, Seoul 07061, Republic of Korea; Department of Orthopaedic Surgery, Yanbian University Hospital, 1327 Juzi St, Yanji 133000, Jilin Province, China.

Department of Basic Science, Hongik University, 94 Wausan-ro, Mapo-Gu, Seoul 04066, Republic of Korea.

出版信息

Spine J. 2017 Oct;17(10):1529-1536. doi: 10.1016/j.spinee.2017.05.014. Epub 2017 May 15.

Abstract

BACKGROUND CONTEXT

Activin A/BMP-2 chimera (AB204) could promote bone healing more effectively than recombinant bone morphogenetic protein 2 (rhBMP-2) with much lower dose in a rodent model, but there is no report about the effectiveness of AB204 in a large animal model.

PURPOSE

The purpose of this study was to compare the osteogenesis and fusion rate between AB204 and rhBMP-2 using biphasic calcium phosphate (BCP) as a carrier in a beagle's posterolateral lumbar fusion model.

STUDY DESIGN

This is a randomized control animal study.

METHODS

Seventeen male beagle dogs were included. Bilateral posterolateral fusion was performed at the L1-L2 and L4-L5 levels. Biphasic calcium phosphate (2 cc), rhBMP-2 (50 µg)+BCP (2 cc), or AB204 (50 µg)+BCP (2 cc) were implanted into the intertransverse space randomly. X-ray was performed at 4 and 8 weeks. After 8 weeks, the animals were sacrificed, and new bone formation and fusion rate were evaluated by manual palpation, computed tomography (CT), and undecalcified histology.

RESULTS

The AB204 group showed significantly higher fusion rate (90%) than the rhBMP-2 group (15%) or the Osteon group (6.3%) by manual palpation. On x-ray and CT assessment, fusion rate and the volume of newly formed bone were also significantly higher in AB204 group than other groups. In contrast, more osteolysis was found in rhBMP-2 group (40%) than in AB204 group (10%) on CT study. In histologic results, new bone formation was sufficient between transverse processes in AB204 group, and obvious trabeculation and bone remodeling were observed. But in rhBMP-2 group, new bone formation was less than AB204 group and osteolysis was observed between the intertransverse spaces.

CONCLUSIONS

A low dose of AB204 with BCP as a carrier significantly promotes the fusion rate in a large animal model when compared with the rhBMP-2. These findings demonstrate that AB204 could be an alternative to rhBMP-2 to improve fusion rate.

摘要

背景

在啮齿动物模型中,激活素 A/BMP-2 嵌合体(AB204)比重组骨形态发生蛋白 2(rhBMP-2)以更低的剂量更有效地促进骨愈合,但在大动物模型中尚无关于 AB204 有效性的报道。

目的

本研究旨在比较 AB204 和 rhBMP-2 与双相磷酸钙(BCP)作为载体在比格犬后路腰椎融合模型中的成骨和融合率。

研究设计

这是一项随机对照动物研究。

方法

纳入 17 只雄性比格犬。双侧后路在 L1-L2 和 L4-L5 水平进行融合。将双相磷酸钙(2cc)、rhBMP-2(50μg)+BCP(2cc)或 AB204(50μg)+BCP(2cc)随机植入横突间。在 4 周和 8 周时进行 X 线检查。8 周后,通过触诊、计算机断层扫描(CT)和未脱钙组织学评估新骨形成和融合率。

结果

AB204 组的融合率(90%)明显高于 rhBMP-2 组(15%)或 Osteon 组(6.3%)。通过 X 线和 CT 评估,AB204 组的融合率和新骨形成体积也明显高于其他组。相比之下,rhBMP-2 组的 CT 研究中发现更多的骨溶解(40%),而 AB204 组的骨溶解(10%)较少。在组织学结果中,AB204 组的横突间有足够的新骨形成,并且观察到明显的小梁和骨重塑。但是在 rhBMP-2 组中,新骨形成少于 AB204 组,并且在横突间观察到骨溶解。

结论

低剂量的 AB204 与 BCP 作为载体在大型动物模型中与 rhBMP-2 相比显著提高了融合率。这些发现表明 AB204 可以替代 rhBMP-2 来提高融合率。

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