阿司匹林对兔桡骨骨切开模型骨愈合的影响。

Effect of aspirin on bone healing in a rabbit ulnar osteotomy model.

机构信息

Department of Orthopaedics and Rehabilitation, University of Iowa Hospitals and Clinics, 200 Hawkins Drive, Iowa City, IA 52242, USA.

出版信息

J Bone Joint Surg Am. 2013 Mar 20;95(6):488-96. doi: 10.2106/JBJS.L.00462.

DOI:10.2106/JBJS.L.00462

PMID:23407637

Abstract

BACKGROUND

Aspirin is frequently prescribed following orthopaedic surgery. Although there is substantial evidence that some nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with delayed bone healing, there have been few studies of the effects of aspirin on bone healing and, to our knowledge, none on the effects of physiologic dosages.

METHODS

Following ulnar osteotomy, fifty-six rabbits were administered a placebo (nine rabbits), indomethacin (nine rabbits given 12.5 mg/kg daily), or aspirin at various doses and schedules (2.7 mg/kg daily for ten rabbits, 10 mg/kg daily for nine rabbits, 50 mg/kg twice daily for ten rabbits, and 100 mg/kg three times daily for nine rabbits). The aspirin doses were chosen to span the clinical dosing range. The indomethacin group served as a positive control and as a relative comparison with the effect of aspirin. Radiographs were obtained every two weeks and the animals were killed at eight weeks. Mechanical testing was performed on all rabbits except for six selected for histological evaluation.

RESULTS

Aspirin delayed bone healing, as demonstrated radiographically and with mechanical testing, in a dose-dependent fashion at salicylate levels equivalent to those resulting from typical human dosing (low-dose aspirin). Receiver operating characteristic analysis demonstrated a plasma salicylate threshold above 20.7 μg/mL predicting delayed bone healing. This approximates a single human dose of 325 mg. Salicylate levels above this threshold were associated with delayed bone healing similar to that caused by indomethacin. Aspirin dosing frequency did not affect bone healing. Mechanical testing was highly predictive of radiographic healing. The interobserver reliability of radiographic assessment of healing at six and eight weeks (kappa = 0.83 and 0.79, respectively) compared favorably with interobserver reliability in previous studies assessing cortical bridging.

CONCLUSIONS

In a rabbit ulnar osteotomy model, aspirin delayed bone healing with a threshold equivalent to a human dose of 325 mg.

摘要

背景

骨科手术后常开具阿司匹林。虽然有大量证据表明某些非甾体抗炎药（NSAIDs）与延迟骨愈合有关，但很少有研究阿司匹林对骨愈合的影响，据我们所知，也没有研究过生理剂量的阿司匹林。

方法

在尺骨切开术后，将 56 只兔子分为四组：安慰剂组（9 只）、吲哚美辛组（9 只，每天给予 12.5mg/kg）、不同剂量和方案的阿司匹林组（每天 2.7mg/kg 的 10 只兔子、每天 10mg/kg 的 9 只兔子、每天两次 50mg/kg 的 10 只兔子和每天三次 100mg/kg 的 9 只兔子）。选择阿司匹林剂量范围涵盖临床用药范围。吲哚美辛组作为阳性对照组，并与阿司匹林的作用进行相对比较。每两周拍摄 X 光片，8 周后处死动物。除 6 只用于组织学评估的兔子外，所有兔子均进行机械测试。

结果

阿司匹林以剂量依赖性方式延迟骨愈合，影像学和机械测试结果均表明，在水杨酸盐水平相当于典型人类剂量（小剂量阿司匹林）时。受试者工作特征分析显示，血浆水杨酸盐阈值超过 20.7μg/ml 可预测骨愈合延迟。这相当于人类单次剂量 325mg。水杨酸盐水平超过此阈值与吲哚美辛引起的骨愈合延迟相似。阿司匹林的给药频率不影响骨愈合。机械测试对 X 光愈合的预测性很高。六周和八周时 X 光片愈合评估的观察者间可靠性（kappa 值分别为 0.83 和 0.79）优于以前评估皮质桥接的研究中的观察者间可靠性。