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重组人骨形态发生蛋白-7促进牵张成骨过程中再生骨的骨化

Acceleration of regenerate ossification during distraction osteogenesis with recombinant human bone morphogenetic protein-7.

作者信息

Mizumoto Yoshihiko, Moseley Timothy, Drews Michael, Cooper Virgil N, Reddi A Hari

出版信息

J Bone Joint Surg Am. 2003;85-A Suppl 3:124-30. doi: 10.2106/00004623-200300003-00019.

DOI:10.2106/00004623-200300003-00019
PMID:12925619
Abstract

BACKGROUND

Bone-lengthening can be accomplished by means of distraction osteogenesis. In the present study, we examined the effect of a single dose of recombinant human bone morphogenetic protein-7 (rhBMP-7) on the rate of new-bone formation during distraction osteogenesis in the rat.

METHODS

Fourteen Long-Evans rats were randomized into two groups of seven rats each. An external fixator was applied to the left femur, and a transverse osteotomy was performed. One group was treated with rhBMP-7 in an aqueous solvent, and the other group received the solvent alone and served as the control. rhBMP-7 was administered on the day of surgery by means of a single injection into the osteotomy gap. Distraction was started seven days after surgery at a rate of 0.25 mm every twelve hours. Distraction was continued for twenty days, resulting in a total of 10 mm of lengthening. The regenerate was monitored with use of radiographs and bone-mineral-density measurements at the conclusion of distraction and at two and four weeks after the cessation of distraction. The lengthened femora were harvested, and biomechanical studies were carried out to determine the stiffness and maximum torque to failure.

RESULTS

Radiographs showed accelerated regenerate ossification in the BMP-7 group, with a larger amount of new bone compared with the control group. The bone-mineral-density values were dramatically enhanced on Day 20 in the BMP-7 group (103.6 +/- 12.6 mg/cm (2) ) compared with the control group (26.2 +/- 15.1 mg/cm (2) ). These differences continued to be greater at two and four weeks after the cessation of distraction. Normalized values of stiffness (percent stiffness) reached 76.5% +/- 5.4% in the BMP-7 group, compared with 6.6% +/- 0.5% in the control group. The percent maximum torque at failure was 81.1% +/- 1.2% in the BMP-7 group, compared with 20.8% +/- 0.3% in the control group.

CONCLUSION

A single injection of rhBMP-7 at the time of osteotomy surgery stimulated the rate of regenerate ossification and increased bone-mineral density during distraction osteogenesis. The biomechanical properties of the newly formed bone were also increased by BMP-7 injection.

摘要

背景

骨延长可通过牵张成骨来实现。在本研究中,我们检测了单剂量重组人骨形态发生蛋白-7(rhBMP-7)对大鼠牵张成骨过程中新骨形成速率的影响。

方法

将14只Long-Evans大鼠随机分为两组,每组7只。在左股骨上应用外固定器,并进行横向截骨术。一组用rhBMP-7的水性溶剂治疗,另一组仅接受溶剂作为对照。rhBMP-7在手术当天通过单次注射到截骨间隙中给药。术后7天开始牵张,以每12小时0.25毫米的速度进行。牵张持续20天,总共延长10毫米。在牵张结束时以及牵张停止后2周和4周,通过X线片和骨密度测量对再生骨进行监测。收获延长后的股骨,并进行生物力学研究以确定刚度和最大破坏扭矩。

结果

X线片显示BMP-7组再生骨的骨化加速,与对照组相比有更多的新骨。与对照组(26.2±15.1毫克/平方厘米)相比,BMP-7组在第20天时骨密度值显著提高(103.6±12.6毫克/平方厘米)。在牵张停止后2周和4周,这些差异仍然更大。BMP-7组的刚度归一化值(刚度百分比)达到76.5%±5.4%,而对照组为6.6%±0.5%。BMP-7组的最大破坏扭矩百分比为81.1%±1.2%,对照组为20.8%±0.3%。

结论

截骨手术时单次注射rhBMP-7可刺激牵张成骨过程中再生骨的骨化速率并增加骨密度。注射BMP-7还可提高新形成骨的生物力学性能。

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