Chinese Journal of Tissue Engineering Research ›› 2020, Vol. 24 ›› Issue (5): 803-810.doi: 10.3969/j.issn.2095-4344.1888
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Xie Chengxin1, Yu Chengqiang1, Wang Wei1, Wang Chenglong2, Yin Dong2
Received:
2019-05-13
Revised:
2019-05-25
Accepted:
2019-07-05
Online:
2020-02-18
Published:
2020-01-15
Contact:
Yin Dong, MD, Master’s supervisor, Chief physician, The People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning 530021, Guangxi Zhuang Autonomous Region, China
Wang Chenglong, Doctoral candidate, The People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning 530021, Guangxi Zhuang Autonomous Region, China
About author:
Xie Chengxin, Master candidate, Graduate School of Guangxi University of Chinese Medicine, Nanning 530200, Guangxi Zhuang Autonomous Region, China
CLC Number:
Xie Chengxin, Yu Chengqiang, Wang Wei, Wang Chenglong, Yin Dong. Meta-analysis of bone morphogenetic protein versus autologous bone grafting for limb long bone nonunion[J]. Chinese Journal of Tissue Engineering Research, 2020, 24(5): 803-810.
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最终纳入8篇文献,共10个对照研究(“Hackl,2017年”包含3个随机对照研究)。其中,4篇为随机对照研究[15-17,19],4篇为非随机对照研究[18,20-22],多为30-124例的小样本量研究,共计613例骨不连患者;4篇研究中的观察组采用骨形态发生蛋白联合自体骨移植[16-17,19,22],2篇研究的观察组单用骨形态发生蛋白[15,18],1篇研究的观察组采用骨形态发生蛋白联合天然无机骨[21],1篇研究的观察组包含18例单用骨形态发生蛋白和8例骨形态发生蛋白联合自体骨移植的患者[20];纳入的8篇文献中所有对照组均为自体骨移植,且所有患者(包含观察组和对照组)均进行机械固定(髓内钉、钢板、螺钉、微创稳定系统、外固定等)。纳入文献质量评价及风险评估结果见图2,纳入研究的基本特征见表1,2。 "
对纳入的每项研究剔除1次,剩余研究做合并分析,此敏感性分析结果显示当剔除“Zimmermann,2009年”的研究后,异质性改变明显(I2=0%,P=0.79),但对结果影响较小[RR=0.97,95%CI(0.92,1.02),P=0.22]。分析产生异质性的原因:“Zimmermann,2009年”的研究中:①所有病例均有自体骨移植修复失败的既往史,骨形态发生蛋白作为全新的局部刺激物可能对这些患者具有更好的反应性。该研究结果认为在多次手术失败的病例中,骨形态发生蛋白具有更高的功效;②骨形态发生蛋白组的病例数相比对照组较少,也可能导致异质性产生。 根据观察组干预措施,仅纳入4篇骨形态发生蛋白联合自体骨移植的研究[16-17,19,22]。各组间无统计学异质性(I2=0%,P=0.89),采用固定效应模型,结果显示骨形态发生蛋白联合自体骨移植与对照组的术后愈合率比较差异无显著性意义[RR=0.96,95%CI(0.89,1.04),P=0.36],见图4;仅纳入2篇单用骨形态发生蛋白的研究[15,18],两组研究间无统计学异质性(I2=0%,P=0.48),采用固定效应模型,结果显示单用骨形态发生蛋白与对照组的术后愈合率比较差异无显著性意义[RR=0.84,95%CI(0.67,1.05),P=0.13],见图5。 "
2.2.6 手术时间和出血量 2篇文献报道了手术时间[18,22]、出血量[18],但由于两研究间骨形态发生蛋白组的干预措施有差异,未采取合并分析。“Yin,2017年”的研究中报道了手术时间的比较,包括骨形态发生蛋白联合自体骨移植组26例和对照组21例,手术时间分别为(70.96±13.34) min和(101.67±12.78) min,两组比较差异有显著性意义(P < 0.01),表明骨形态发生蛋白联合自体骨移植组比对照组的手术时间更短。“Tressler,2011年”的研究报道了手术时间和术中出血量的比较,包括单用骨形态发生蛋白组19例和对照组74例,手术时间分别为(168.9±86.5),(257.9±93) min,两组比较差异有显著性意义(P < 0.01),表明单用骨形态发生蛋白组比对照组的手术时间更短;术中出血量分别为(331.6±357.2),(554.6±447.8) mL,两组比较差异有显著性意义(P=0.02),表明单用骨形态发生蛋白组比对照组的术中出血量更少。 2.2.7 住院时间和住院费用 2篇文献分别报道了住院时间[18]、住院费用情况[22]。“Tressler,2011年”的研究报道了住院时间的比较,单用骨形态发生蛋白组住院时间为(3.2±2.6) d,对照组住院时间为(3.8±2.5) d,两组住院时间的比较差异无显著性意义(P=0.37)。“Yin,2017年”的研究报道了平均住院费用的比较,骨形态发生蛋白联合自体骨移植组和对照组的住院费用分别为(2.65±0.34),(2.14±0.35)万元,两组比较差异有显著性意义(P < 0.01),表明骨形态发生蛋白联合自体骨移植组比对照组的住院费用更高。 2.3 发表偏倚分析 使用RevMan 5.1软件对文献进行发表偏倚分析。通过漏斗图进行评价发表偏倚时,原则上纳入的研究数不应少于10篇,否则会导致漏斗图的检验能力下降。此次Meta分析共纳入8篇文献,但包含了10个对照研究,因此有必要进行发表偏倚漏斗图分析。对术后愈合率进行偏倚风险评估,结果显示漏斗图呈散点不对称分布,表明研究可能存在一定的发表偏倚,见图11。 "
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