Department of Orthopaedic Surgery, Keck School of Medicine, Elaine Stevely Hoffman Medical Research Center, University of Southern California, HMR 710, 2011 Zonal Ave., Los Angeles, CA, 90033, USA.
Vericel Corporation, Cambridge, MA, USA.
Eur Spine J. 2017 Nov;26(11):2763-2772. doi: 10.1007/s00586-017-5149-9. Epub 2017 May 25.
The aim of our study was to determine the effect of Oxy133 and rhBMP2 on fusion rates and new bone formation in a rat posterolateral fusion (PLF) model. Furthermore, we examined whether Oxy133 could inhibit the adipogenesis that is often present in rhBMP2-induced fusions.
Sixty-four male Lewis rats underwent two levels PLF (L3-L5). All animals were randomly divided into eight groups based on the test compound that they received: control (DMSO), low-dose rhBMP2 (0.5 µg), high-dose rhBMP2 (5 µg), low-dose Oxy133 (5 mg), high-dose Oxy133 (20 mg), low rhBMP2 + high Oxy133, high rhBMP2 + high Oxy133, and low rhBMP2 + low Oxy133. Fusion rates were assessed 8 weeks after surgery with manual palpation and plain radiographs. Bone parameters were measured using microCT. Histology was used to evaluate adipogenesis.
No fusion was observed in the control group. Based on the manual palpation, 100% fusion was observed in all other groups except in the low-dose rhBMP2 group (69%). At 8 weeks based on X-rays, 100% fusion was observed in the following groups: high-dose rhBMP2, low-dose Oxy133, and low rhBMP2 + low Oxy133. In the other groups, the fusion rates were between 95 and 97%, except for the low rhBMP2 group (72%). We observed similar values in BV/TV ratio at L3-4 when Oxy133 groups were compared to rhBMP2 groups alone (44.62% in high-dose Oxy133 vs. 41.47% in high-dose rhBMP2 and 47.18% in low-dose Oxy133 vs. 54.98% in low-dose rhBMP2). Trabecular thickness was slightly lower in Oxy133 groups compared to rhBMP2 when comparing low- and high-dose groups from each group (118.44 µm for high-dose Oxy133 vs. 122.39 µm for high-dose rhBMP2 and 123.51 µm for low-dose Oxy133 vs. 135.74 µm for low-dose rhBMP2). At the same time, trabecular separation was lower in Oxy133 groups compared to rhBMP2 groups. Similar trends in bone parameters were observed at the L4-5 levels. Fusion masses with low- and high-dose Oxy133 had significantly less adipocytes than rhBMP2 groups that showed robust adipocyte formation.
In our study, both low-dose and high-dose Oxy133 produced solid fusions with bone densities similar or higher than in the BMP2 groups. High-dose Oxy133 group had significantly less adipocytes than high- or low-dose rhBMP2 groups. Furthermore, high-dose Oxy133 was able to significantly inhibit high-dose BMP2-induced adipogenesis when combined together. Consistent with the previous reports, our preliminary findings suggest that Oxy133 has a significant potential as an alternative to rhBMP2 in spine fusion.
我们的研究旨在确定 Oxy133 和 rhBMP2 对大鼠后路融合（PLF）模型中的融合率和新骨形成的影响。此外，我们还研究了 Oxy133 是否可以抑制 rhBMP2 诱导融合中常见的脂肪生成。
64 只雄性 Lewis 大鼠接受了两个水平的 PLF（L3-L5）。所有动物根据接受的测试化合物随机分为 8 组：对照组（DMSO）、低剂量 rhBMP2（0.5μg）、高剂量 rhBMP2（5μg）、低剂量 Oxy133（5mg）、高剂量 Oxy133（20mg）、低 rhBMP2+高 Oxy133、高 rhBMP2+高 Oxy133 和低 rhBMP2+低 Oxy133。术后 8 周通过手动触诊和普通 X 线评估融合率。使用 microCT 测量骨参数。组织学用于评估脂肪生成。
对照组未观察到融合。基于手动触诊，除低剂量 rhBMP2 组（69%）外，其他所有组均观察到 100%的融合。基于 X 射线，在以下组中观察到 100%的融合：高剂量 rhBMP2、低剂量 Oxy133 和低 rhBMP2+低 Oxy133。在其他组中，融合率在 95%至 97%之间，除了低剂量 rhBMP2 组（72%）。当将 Oxy133 组与 rhBMP2 组单独比较时，我们在 L3-4 处观察到相似的 BV/TV 比值：高剂量 Oxy133 为 44.62%，高剂量 rhBMP2 为 41.47%，低剂量 Oxy133 为 47.18%，低剂量 rhBMP2 为 54.98%。与 rhBMP2 相比，Oxy133 组的小梁厚度略低，当比较每组的低剂量和高剂量组时（高剂量 Oxy133 为 118.44μm，高剂量 rhBMP2 为 122.39μm，低剂量 Oxy133 为 123.51μm，低剂量 rhBMP2 为 135.74μm）。同时，Oxy133 组的小梁分离度低于 rhBMP2 组。在 L4-5 水平也观察到了类似的骨参数趋势。低剂量和高剂量 Oxy133 的融合质量的脂肪细胞明显少于 rhBMP2 组，rhBMP2 组显示出明显的脂肪细胞形成。
在我们的研究中，低剂量和高剂量 Oxy133 均产生了具有相似或高于 BMP2 组骨密度的坚固融合。高剂量 Oxy133 组的脂肪细胞明显少于高剂量或低剂量 rhBMP2 组。此外，当高剂量 Oxy133 与高剂量 BMP2 联合使用时，它能够显著抑制高剂量 BMP2 诱导的脂肪生成。与之前的报告一致，我们的初步发现表明，Oxy133 作为 rhBMP2 在脊柱融合中的替代物具有显著的潜力。
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