Department of Orthopaedic Surgery, Faculty of Medicine, Oita University, Oita 879-5593, Japan.
School of Physical Therapy, Faculty of Rehabilitation, Reiwa Health Sciences University, Fukuoka 811-0213, Japan.
Int J Mol Sci. 2024 Mar 25;25(7):3655. doi: 10.3390/ijms25073655.
Both bone morphogenetic protein 2 (BMP-2) and abaloparatide are used to promote bone formation. However, there is no consensus about their optimal administration. We investigated the optimal administration theory for the pairing of BMP-2 and abaloparatide in a rat spinal fusion model. Group I was only implanted in carriers and saline. Carriers with 3 µg of recombinant human BMP-2 (rhBMP-2) were implanted in other groups. Abaloparatide injections were administered three times a week for group III (for a total amount of 120 µg/kg in a week) and six times a week for group IV (for a total amount of 120 µg/kg in a week) after surgery. They were euthanized 8 weeks after the surgery, and we explanted their spines at that time. We assessed them using manual palpation tests, radiography, high-resolution micro-computed tomography (micro-CT), and histological analysis. We also analyzed serum bone metabolism markers. The fusion rate in Groups III and IV was higher than in Group I, referring to the manual palpation tests. Groups III and IV recorded greater radiographic scores than those in Groups I and II, too. Micro-CT analysis showed that Tbs. Sp in Groups III and IV was significantly lower than in Group I. Tb. N in Group IV was significantly higher than in Group I. Serum marker analysis showed that bone formation markers were higher in Groups III and IV than in Group I. On the other hand, bone resorption markers were lower in Group IV than in Group I. A histological analysis showed enhanced trabecular bone osteogenesis in Group IV. Frequent administration of abaloparatide may be suitable for the thickening of trabecular bone structure and the enhancement of osteogenesis in a rat spinal fusion model using BMP-2 in insufficient doses.
骨形态发生蛋白 2（BMP-2）和abaloparatide 均可促进骨形成。然而，关于它们的最佳给药方式尚无共识。我们在大鼠脊柱融合模型中研究了 BMP-2 和 abaloparatide 联合应用的最佳给药理论。第 I 组仅植入载体和生理盐水。其他组植入含有 3µg 重组人 BMP-2（rhBMP-2）的载体。手术后，第 III 组每周注射 abaloparatide 3 次（一周总量为 120µg/kg），第 IV 组每周注射 6 次（一周总量为 120µg/kg）。手术后 8 周处死，取出脊柱。我们通过手动触诊测试、影像学、高分辨率微计算机断层扫描（micro-CT）和组织学分析评估它们。还分析了血清骨代谢标志物。与 I 组相比，III 组和 IV 组的融合率更高，触诊结果提示。III 组和 IV 组的影像学评分也高于 I 组和 II 组。micro-CT 分析显示，III 组和 IV 组的 Tbs.Sp 明显低于 I 组。IV 组的 Tb.N 明显高于 I 组。血清标志物分析显示，III 组和 IV 组的骨形成标志物高于 I 组。另一方面，IV 组的骨吸收标志物低于 I 组。组织学分析显示，IV 组增强了小梁骨成骨。在 BMP-2 剂量不足的大鼠脊柱融合模型中，频繁给予 abaloparatide 可能适合小梁骨结构增厚和增强成骨作用。
