Simvastatin locally applied from a biodegradable coating of osteosynthetic implants improves fracture healing comparable to BMP-2 application
Simvastatin locally applied from a biodegradable coating of osteosynthetic implants improves fracture healing comparable to BMP-2 application
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DOI：
10.1016/j.bone.2009.05.010
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发表时间：
2009-09-01
期刊：
影响因子：
4.1
通讯作者：
Wildemann, B.
中科院分区：
文献类型：
--
作者：
Pauly, S.;Luttosch, F.;Wildemann, B.
许多临床和实验研究表明他汀类药物对骨形成和骨折愈合的影响。辛伐他汀被证明可以增加骨形态发生蛋白(BMP-2)的表达，BMP-2是最有效的靶向成骨的生长因子之一。在这项研究中，研究了从植入物的生物活性聚合物涂层局部应用辛伐他汀对骨折愈合的影响。对5月龄SD大鼠右侧胫骨进行闭合性骨折。髓内稳定是通过未涂层与仅有聚合物涂层与聚合物加药物涂层的钛克氏针实现的。将受试物质(辛伐他汀低剂量或高剂量或骨形态发生蛋白-2)加入到聚(D，L-丙交酯)的可生物降解层中。分别于28d和42d取材，进行生物力学测试(扭转刚度和最大载荷)和组织形态计量学分析。放射学结果显示，在两个时间点，骨形态发生蛋白-2和辛伐他汀组与未包被组相比，骨痂固结进展。与对照组相比，辛伐他汀高剂量组的扭转刚度增加，最大载荷(D28)显著增加，在d42，这两个参数均显著增加。BMP-2组动物早期最大载荷和最大刚度显著增加，42天后扭转刚度显著增加。组织形态计量学分析显示，BMP-2组在28天软骨面积显著减少。即使在42天时，辛伐他汀高剂量组和BMP-2组骨膜骨痂之间的矿化面积增加，但在两个时间点都没有检测到与未涂层组相比有显著差异。然而，高辛伐他汀治疗的动物在42天时显示骨膜骨痂内的软骨面积显著减少。本研究揭示了局部应用辛伐他汀的剂量依赖效应和促进骨折愈合的作用。在这项研究中，生物力学、放射学和组织形态计量学特性显示出与BMP-2处理的动物相似的结果。(C)2009 Elsevier Inc.保留所有权利。
Many clinical and experimental investigations address the influence of statins on bone formation and fracture healing. Simvastatin was shown to increase the expression of Bone morphogenetic protein (BMP-2), which is one of the most potent growth factors targeting bone formation. In this study, the effect of simvastatin locally applied from a bioactive polymer coating of implants on fracture healing was investigated. A closed fracture of the right tibia of 5-month-old Sprague-Dawley rats was performed. Intramedullary stabilization was achieved with uncoated vs. polymer-only coated vs. polymer plus drug coated titanium Kirschner wires. Test substances (either simvastatin low- or high dosed or BMP-2) were incorporated into a biodegradable layer Of poly(D,L-lactide). Tibiae were harvested after 28 or 42 days, respectively and underwent biomechanical testing (torsional stiffness and maximum load) and histomorphometric analysis. Radiographic results demonstrated progressed callus consolidation in the BMP-2- and simvastatin-treated groups compared to the uncoated group at both timepoints. The simvastatin-high-dosed group revealed an increased torsional stiffness and significantly elevated maximum load (d 28) compared to control group as well as a significant increase in both parameters at d 42. BMP-2-treated animals showed significantly elevated maximum load and stiffness at the early timepoint and elevated torsional stiffness after d 42.The histomorphometric analysis revealed a significantly decreased cartilage area for BMP-2 treated animals at d 28. Even though an increase of mineralized areas among periosteal callus was found at d 42 for simvastatin-high as well as BMP-2 treated animals, no significant difference could be detected at both timepoints compared to the uncoated group. However, simvastatin-high treated animals revealed significantly reduced cartilage areas within the periosteal callus at d 42. The present study revealed a dose-dependent effect and improved fracture healing under local application of simvastatin. Biomechanical, radiographic and histomorphometric properties showed comparable results to BMP-2- treated animals in this study. (C) 2009 Elsevier Inc. All rights reserved.