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Osteogenic effects in a rat osteoporosis model and femur defect model by simvastatin microcrystals
Annals of the New York Academy of Sciences ( IF 5.2 ) Pub Date : 2020-10-23 , DOI: 10.1111/nyas.14513
Junxiong Zhu 1 , Chenggui Zhang 1 , Jialin Jia 1 , Hong Wang 1, 2 , Huijie Leng 1, 2 , Yingsheng Xu 3 , Cuishuan Wu 4 , Qiang Zhang 5 , Chunli Song 1, 2
Affiliation  

Simvastatin is a translational drug that may be used to induce local bone formation. In this study, simvastatin microcrystals were made by a wet media milling method, and then we verified the osteogenic effect of the microcrystals in rat ovariectomy (OVX)-induced osteoporosis and femur defect models. For the osteoporosis model, we delivered simvastatin microcrystals to the tibia with poloxamer hydrogels via an intraosseous injection. Bone mineral density and the ultimate force of the treated tibia were significantly improved after injection of simvastatin microcrystals at 0.5 and 1 mg compared with the OVX or 0-mg control groups. For the femur defect model, simvastatin microcrystals were incorporated in clinically used calcium phosphate cements (CPCs) as an implant. Quantitative analysis of bone regeneration by microcomputed tomography (μCT) showed improved bone morphology with simvastatin microcrystals at 50 and 100 μg, compared with the CPC vehicle. A semiquantitative scale for histology assessment further demonstrated a higher bone regeneration score in the drug-loaded groups. Our study shows that simvastatin microcrystals can promote bone formation by local delivery using a poloxamer hydrogel or CPC, which may be translationally useful.

中文翻译:

辛伐他汀微晶对大鼠骨质疏松模型和股骨缺损模型的成骨作用

辛伐他汀是一种转化药物,可用于诱导局部骨形成。在这项研究中,辛伐他汀微晶是通过湿介质研磨法制备的,然后我们验证了微晶在大鼠卵巢切除术 (OVX) 诱导的骨质疏松症和股骨缺损模型中的成骨作用。对于骨质疏松症模型,我们通过骨内注射将辛伐他汀微晶和泊洛沙姆水凝胶输送到胫骨。与 OVX 或 0-mg 对照组相比,注射 0.5 和 1 毫克辛伐他汀微晶后,骨矿物质密度和治疗胫骨的极限力显着提高。对于股骨缺损模型,将辛伐他汀微晶掺入临床使用的磷酸钙骨水泥 (CPC) 作为植入物。通过显微计算机断层扫描 (μCT) 对骨再生的定量分析表明,与 CPC 载体相比,50 和 100 μg 的辛伐他汀微晶可改善骨形态。用于组织学评估的半定量量表进一步证明,载药组具有更高的骨再生评分。我们的研究表明,辛伐他汀微晶可以通过使用泊洛沙姆水凝胶或 CPC 的局部递送来促进骨形成,这可能具有转化作用。
更新日期:2020-10-23
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