Department of Orthopedic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, Japan.
Department of Orthopedic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, Japan.
Spine J. 2020 May;20(5):821-829. doi: 10.1016/j.spinee.2019.12.014. Epub 2019 Dec 31.
The effects of using off-label recombinant human bone morphogenetic protein (rhBMP)-2 for interbody fusion are controversial. Although animal models of posterolateral fusion are well-established, establishing animal models to validate the safety and efficacy of interbody fusion is difficult, which may contribute to the inconsistent clinical results.
To develop a novel animal model of interbody fusion in rat coccygeal vertebrae without destroying bony endplates.
An experimental animal study.
Forty-five male Sprague-Dawley rats underwent coccygeal interbody fusion without violating vertebral endplates. The animals were divided into three different groups based on the materials that were implanted into the interbody space (1) allogeneic iliac bone (IB) alone (IB group), (2) IB and 3 µg of rhBMP-2 (BMP low-dose group), or (3) IB and 10 µg of rhBMP-2 (BMP high-dose group). Fusion rates were investigated using microcomputed tomography 6 weeks after the operation. The incidence of adverse events, including soft-tissue swelling, delayed wound healing, osteolysis, and ectopic bone formation were evaluated. The total number of adverse events (using the adverse event score) in each group and the swelling ratio (calculated using the surgical site tissue volume [TV; TV on postoperative day 1/preoperative TV]) were also evaluated.
The fusion rates in the BMP low- and high-dose groups (33.3% and 46.7%) were not significantly different, but both were significantly higher than that in the IB group (0%) (p=.042 and .006, respectively). Significant differences in the incidence of osteolysis, adverse event scores, and swelling ratios were observed only between the BMP high-dose and IB groups (p=.043, .006 and .014, respectively).
We developed a novel rat model of interbody fusion in which the vertebral endplates were not violated, reflecting the normal clinical setting. rhBMP-2 use increased the fusion rate, but a higher dose of rhBMP-2 did not lead to a higher fusion rate than that for low-dose rhBMP-2; conversely, it led to an increase in the occurrence of adverse events.
This novel rat model of coccygeal interbody fusion that preserved bony endplates has clinical significance for validating the effectiveness of biologics or bone graft substitutes before clinical trial.
使用非适应证重组人骨形态发生蛋白（rhBMP）-2 进行椎间融合的效果存在争议。尽管已经建立了用于后外侧融合的动物模型，但建立验证椎间融合安全性和有效性的动物模型较为困难，这可能导致临床结果不一致。
开发一种新型的大鼠尾骨椎间融合动物模型，无需破坏骨性终板。
实验动物研究。
45 只雄性 Sprague-Dawley 大鼠在不破坏椎骨终板的情况下进行尾骨椎间融合。根据植入椎间空间的材料，将动物分为三组：（1）单纯同种异体髂骨（IB）（IB 组），（2）IB 和 3 µg rhBMP-2（低剂量 BMP 组），或（3）IB 和 10 µg rhBMP-2（高剂量 BMP 组）。术后 6 周，使用微计算机断层扫描评估融合率。评估不良事件的发生率，包括软组织肿胀、伤口愈合延迟、骨溶解和异位骨形成。还评估了每组的总不良事件数（使用不良事件评分）和肿胀比（术后第 1 天/术前 TV[手术部位组织体积 TV]计算）。
低剂量 BMP 和高剂量 BMP 组的融合率（33.3%和 46.7%）无显著差异，但均显著高于 IB 组（0%）（分别为 p=.042 和.006）。仅在高剂量 BMP 和 IB 组之间观察到骨溶解、不良事件评分和肿胀比的发生率存在显著差异（p=.043、.006 和.014）。
我们开发了一种新型的大鼠椎间融合模型，其中不破坏椎骨终板，反映了正常的临床情况。rhBMP-2 的使用增加了融合率，但高剂量 rhBMP-2 并未导致融合率高于低剂量 rhBMP-2，反而导致不良事件发生率增加。
这种新型的保留骨性终板的大鼠尾骨椎间融合模型对验证生物制剂或骨移植物替代品在临床试验前的有效性具有临床意义。
