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骨硬化蛋白抗体增加骨量并增强大鼠模型中的种植体固定。

Sclerostin antibody increases bone volume and enhances implant fixation in a rat model.

机构信息

Department of Anatomy and Cell Biology, Rush Medical College, Rush University Medical Center, 600 South Paulina Street, Room 507, AcFac, Chicago, IL 60612, USA.

出版信息

J Bone Joint Surg Am. 2012 Sep 19;94(18):1670-80. doi: 10.2106/JBJS.K.00344.

Abstract

BACKGROUND

Previous studies have demonstrated that sclerostin blockade is anabolic for bone. This study examined whether systemic administration of sclerostin antibody would increase implant fixation and peri-implant bone volume in a rat model.

METHODS

Titanium cylinders were placed in the femoral medullary canal of ninety male Sprague-Dawley rats. One-half of the rats (n=45) received murine sclerostin antibody (Scl-Ab, 25 mg/kg, twice weekly) and the other one-half (n=45) received saline solution. Equal numbers of rats from both groups were sacrificed at two, four, or eight weeks after the implant surgery and the femora were examined by microcomputed tomography, mechanical pull-out testing, and histology.

RESULTS

Fixation strength in the two groups was similar at two weeks but was 1.9-fold greater at four weeks (p=0.024) and 2.2-fold greater at eight weeks (p<0.001) in the rats treated with sclerostin antibody. At two weeks, antibody treatment led to increased cortical area, with later increases in cortical thickness and total cross-sectional area. Significant differences in peri-implant trabecular bone were not evident until eight weeks but included increased bone volume per total volume, bone structure that was more plate-like, and increased trabecular thickness and number. Changes in bone architecture in the intact contralateral femur tended to precede the peri-implant changes. The peri-implant bone properties accounted for 61% of the variance in implant fixation strength, 32% of the variance in stiffness, and 63% of the variance in energy to failure. The implant fixation strength at four weeks was approximately equivalent to the strength in the control group at eight weeks.

CONCLUSIONS

Sclerostin antibody treatment accelerated and enhanced mechanical fixation of medullary implants in a rat model by increasing both cortical and trabecular bone volume.

摘要

背景

先前的研究表明,阻断硬骨素可促进骨形成。本研究旨在探究在大鼠模型中,全身性给予硬骨素抗体是否能增加种植体固定和种植体周围骨量。

方法

将钛圆柱体植入 90 只雄性 Sprague-Dawley 大鼠的股骨髓腔中。其中一半大鼠(n=45)接受鼠源硬骨素抗体(Scl-Ab,25mg/kg,每周两次)治疗,另一半(n=45)接受生理盐水溶液治疗。在种植手术后 2、4 或 8 周时,每组处死等量大鼠,通过微计算机断层扫描、机械拔出试验和组织学检查评估股骨。

结果

两组大鼠在 2 周时的固定强度相似,但在 Scl-Ab 治疗组的 4 周(p=0.024)和 8 周(p<0.001)时固定强度分别增加了 1.9 倍和 2.2 倍。在 2 周时,抗体治疗导致皮质面积增加,随后皮质厚度和总横截面积增加。直到 8 周时,种植体周围小梁骨的差异才明显,但包括增加了总体积的骨量、更板状的骨结构、增加的小梁厚度和数量。完整对侧股骨的骨结构变化倾向于先于种植体周围的变化。种植体周围骨特性解释了种植体固定强度的 61%、刚度的 32%和破坏能的 63%的变异性。4 周时的种植体固定强度大约相当于 8 周时对照组的强度。

结论

硬骨素抗体治疗通过增加皮质和小梁骨量,加速并增强了大鼠模型中髓内植入物的机械固定。

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