Background

Fracture healing complications are associated with significant healthcare and economic burden. In this study, we aimed to investigate how the combined administration of local simvastatin and ezetimibe into the femoral defect of the animal model affects the bone-healing process in comparison with their monotherapy.

Methods

A total of 32 four-month-old adult male Wistar rats were randomized into the four study groups: simvastatin + ezetimibe-loaded nanofibers (group 1), simvastatin-loaded nanofibers (group 2), ezetimibe-loaded nanofibers (group 3), and non-loaded nanofibers (group 4). After the generation of femoral defects, the predesigned nanofibers were locally administered into the defect site. The healing measures were serum and bone osteoprotegerin (OPG) expression, pathologic evaluation of union (Allen's fracture healing scores), and radiographic evaluation of bone density (Hounsfield scale) at weeks 2 and 4.

Results

The improvement of all evaluated healing measures was remarkably superior in rats that were treated with loaded nanofibers in comparison with the control group. Also, the improvement of all evaluated healing measures was considerably more in the simvastatin-ezetimibe combination therapy group compared to their monotherapy. All the evaluated measures were superior in the ezetimibe monotherapy group compared to the simvastatin monotherapy group.

Conclusion

The cumulative effect of simvastatin and ezetimibe on the induction of bone healing is more significant than the individual effect of these drugs. Therefore, local administration of nanofibers loaded with simvastatin and ezetimibe could be regarded as a promising osteoinductive compound for the acceleration of bone repair.

中文翻译：

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辛伐他汀和/或依泽替米贝纳米纤维对股骨缺损愈合的重要作用：一项实验研究

背景

骨折愈合并发症与重大的医疗保健和经济负担有关。在这项研究中，我们旨在研究与单一疗法相比，将局部辛伐他汀和依折麦布联合给药至动物模型股骨缺损如何影响骨愈合过程。

方法

总共将32只4个月大的成年雄性Wistar大鼠随机分为四个研究组：辛伐他汀+含依折麦布的纳米纤维（第1组），辛伐他汀-载纳米纤维（第2组），依泽替米贝-载纳米纤维（组3）和未加载的纳米纤维（第4组）。在产生股骨缺损后，将预先设计的纳米纤维局部施用于缺损部位。愈合措施包括在第2周和第4周时血清和骨保护素（OPG）的表达，联合的病理评估（艾伦骨折愈合评分）以及骨密度的放射照相评估（霍恩斯菲尔德量表）。

结果

与对照组相比，在用负载纳米纤维治疗的大鼠中，所有评估的治愈措施的改善均明显优于对照组。此外，与单一疗法相比，辛伐他汀-依泽替米贝联合疗法组所有评估的治愈措施的改善幅度更大。依泽替米贝单药治疗组的所有评估指标均优于辛伐他汀单药治疗组。

结论

辛伐他汀和依泽替米贝在诱导骨愈合中的累积作用比这些药物的单独作用更为显着。因此，局部施用载有辛伐他汀和依泽替米贝的纳米纤维可被视为促进骨修复的有希望的骨诱导化合物。