Enhancement of the effects of intermittent parathyroid hormone (1-34) by bone morphogenetic protein in a rat femoral open fracture model
Enhancement of the effects of intermittent parathyroid hormone (1-34) by bone morphogenetic protein in a rat femoral open fracture model
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DOI：
10.1186/s13018-019-1470-9
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发表时间：
2019-11-29
影响因子：
2.6
通讯作者：
Tsumura, Hiroshi
中科院分区：
文献类型：
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作者：
Kanezaki, Shozo;Miyazaki, Masashi;Tsumura, Hiroshi
背景开放性骨折中骨不连是很常见的。骨形态发生蛋白2(BMP-2)和甲状旁腺激素(PTH)已被用于促进骨愈合。我们研究了骨形态发生蛋白-2和甲状旁腺素的联合应用，并考察了它们在大鼠开放性股骨骨折模型上的作用。方法I组(n=11)植入对照载体。II组(n=12)植入含有1mg重组人骨形成蛋白-2(rhBMP-2)的载体。第III组(n=12)，单纯植入载体后注射PTH1-34。IV组(n=11)植入含有1mgrhBMP-2的载体，然后注射PTH1-34。V组(n=11)植入含有10mgrhBMP-2的载体。第VI组(n=11)植入含有10mgrhBMP-2的载体，然后注射PTH1-34。8周后处死大鼠，取出骨折股骨，进行手法触诊、X线片、微电脑断层扫描和组织学分析。结果人工触诊试验显示，III组(66.7%)、IV组(63.6%)、V组(81.8%)和VI组(81.8%)的融合率明显高于I组，V组和VI组的X线评分高于I组。Micro-CT分析显示V组(61.88+/-3.16%)和VI组(71.14+/-3.89%)较I组(58.26+/-1.86%)骨髓密度增加。组织学分析显示，VI组有明显的重塑。结论丰富的重组人骨形态发生蛋白-2和甲状旁腺素联合应用可促进大鼠股骨开放性骨折模型的骨愈合和新骨改建。
Background Nonunion in cases of open fracture is common. Both bone morphogenetic protein 2 (BMP-2) and parathyroid hormone (PTH) have been used to enhance bone healing. We investigated the combination of BMP-2 and PTH and examined the effects on a rat model of open femoral fractures. Methods Group I (n = 11) was implanted with control carrier. Group II (n = 12) was implanted with carrier containing 1 mu g of recombinant human BMP-2 (rhBMP-2). Group III (n = 12) was implanted with carrier alone, followed by injections of PTH 1-34. Group IV (n = 11) was implanted with carrier containing 1 mu g of rhBMP-2, followed by injections of PTH 1-34. Group V (n = 11) was implanted with carrier containing 10 mu g of rhBMP-2. Group VI (n = 11) was implanted with carrier containing 10 mu g of rhBMP-2, followed by injections of PTH 1-34. Rats were euthanized after 8 weeks, and their fractured femurs were explanted and assessed by manual palpation, radiographs, micro-computerized tomography, and histological analysis. Results Manual palpation tests showed that the fusion rates of groups III (66.7%), IV (63.6%), V (81.8%), and VI (81.8%) were considerably higher than those of group I. Groups V and VI had higher radiographic scores compared to group I. Micro-CT analysis revealed enhanced bone marrow density expressed as bone volume/tissue volume in groups V (61.88 +/- 3.16%) and VI (71.14 +/- 3.89%) versus group I (58.26 +/- 1.86%). A histological analysis indicated that group VI had enhanced remodeling. Conclusion The combination of abundant rhBMP-2 and PTH enhanced bone healing and remodeling of newly formed bone in a rat femoral open fracture model.