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盐酸安非他酮对大鼠腰椎融合模型的影响。

The effects of varenicline on lumbar spinal fusion in a rat model.

机构信息

Department of Orthopaedic Surgery, Stanford University Hospital and Clinics, Redwood City, CA, USA.

Orthopedic Stem Cell Research Laboratory, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Department of Orthopedics, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.

出版信息

Spine J. 2020 Feb;20(2):300-306. doi: 10.1016/j.spinee.2019.07.015. Epub 2019 Aug 1.

DOI:10.1016/j.spinee.2019.07.015
PMID:31377475
Abstract

BACKGROUND CONTEXT

Smoking is detrimental to obtaining a solid spinal fusion mass with previous studies demonstrating its association with pseudoarthrosis in patients undergoing spinal fusion. Varenicline is a pharmacologic adjunct used in smoking cessation which acts as a partial agonist of the same nicotinic receptors activated during tobacco use. However, no clinical or basic science studies to date have characterized if varenicline has negative effects on spinal fusion and bone healing by itself.

PURPOSE

Our study's aim was to elucidate whether varenicline affects the frequency or quality of posterolateral spinal fusion in a rodent model at an endpoint of 12 weeks.

STUDY DESIGN

Randomized control trial.

PATIENT SAMPLE

Fourteen male Lewis rats randomly separated into two experimental groups.

OUTCOME MEASURES

Manual palpation of fusion segment, radiography, μCT imaging, and four-point bend.

METHODS

Fourteen male Lewis rats were randomly separated into two experimental groups undergoing L4-L5 posterior spinal fusion procedure followed by daily subcutaneous injections of human dose varenicline or saline (control) for 12 weeks postsurgery. Spine samples were explanted, and fusion was determined via manual palpation of segments by two independent observers. High-resolution radiographs were obtained to evaluate bridging fusion mass. μCT imaging was performed to characterize fusion mass and consolidation. Lumbar spinal fusion units were tested in four-point bending to evaluate stiffness and peak load. Study funding sources include $5000 OREF Grant. There were no applicable financial relationships or conflicts of interest.

RESULTS

At 3 months postsurgery, 12 out of 14 rats demonstrated lumbar spine fusion (86% fused) with no difference in fusion frequency between the varenicline and control groups as detected by manual palpation. High-resolution radiography revealed six out of seven rats (86%) having complete fusion in both groups. μCT showed no significant difference in bone mineral density or bone fraction volume between groups in the region of interest. Biomechanical testing demonstrated no significant different in the average stiffness or peak loads at the fusion site of the varenicline and control groups.

CONCLUSION

Based on the results of our rat study, there is no indication that varenicline itself has a detrimental effect on the frequency and quality of spinal fusion.

摘要

背景

先前的研究表明,吸烟会影响获得坚实的脊柱融合块,与接受脊柱融合的患者的假关节形成有关。伐伦克林是一种用于戒烟的药物辅助手段,它作为一种尼古丁受体的部分激动剂,与烟草使用过程中激活的受体相同。然而,迄今为止,没有临床或基础科学研究来描述伐伦克林本身是否会对脊柱融合和骨愈合产生负面影响。

目的

我们的研究目的是阐明伐伦克林是否会在 12 周的时间内影响啮齿动物模型的后路脊柱融合的频率或质量。

研究设计

随机对照试验。

患者样本

14 只雄性 Lewis 大鼠随机分为两组实验组。

结局测量

融合节段的手动触诊、影像学、μCT 成像和四点弯曲。

方法

14 只雄性 Lewis 大鼠随机分为两组,进行 L4-L5 后路脊柱融合手术,术后每天皮下注射人体剂量的伐伦克林或生理盐水(对照)12 周。取出脊柱标本,由两名独立观察者通过手动触诊节段确定融合情况。获得高分辨率射线照相以评估桥接融合块。μCT 成像用于融合质量和巩固的特征。在四点弯曲中测试腰椎融合单元,以评估刚度和峰值载荷。研究资金来源包括 5000 美元 OREF 赠款。无适用的财务关系或利益冲突。

结果

术后 3 个月,14 只大鼠中有 12 只(86%融合)出现腰椎融合,伐伦克林组和对照组的融合频率无差异,通过手动触诊检测。高分辨率射线照相显示两组中有 6 只(86%)的大鼠完全融合。μCT 显示两组在感兴趣区域的骨矿物质密度或骨体积分数无显著差异。生物力学测试表明,伐伦克林组和对照组融合部位的平均刚度和峰值载荷无显著差异。

结论

根据我们的大鼠研究结果,没有迹象表明伐伦克林本身会对脊柱融合的频率和质量产生不利影响。

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