Chinese Journal of Tissue Engineering Research ›› 2021, Vol. 25 ›› Issue (3): 486-492.doi: 10.3969/j.issn.2095-4344.2944
Xie Chengxin1, Wang Wei1, Wang Chenglong2, Li Qinglong2, Yin Dong2
Received:
2020-03-09
Revised:
2020-03-13
Accepted:
2020-04-03
Online:
2021-01-28
Published:
2020-11-19
Contact:
Yin Dong, MD, Master’s supervisor, Chief physician, Department of Orthopedics, 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
Supported by:
CLC Number:
Xie Chengxin, Wang Wei, Wang Chenglong, Li Qinglong, Yin Dong. Systematic review and meta-analysis of bone morphogenetic protein for the treatment of acute tibial fracture[J]. Chinese Journal of Tissue Engineering Research, 2021, 25(3): 486-492.
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2.1 文献检索结果及质量评价 根据检索策略共检索出526篇可能符合纳入标准的文献,并导入到Endnote X9中进行重复文献的排除,剩余222篇相关文献。然后根据题目、摘要的内容,排除不相关的文献208篇,初步筛选后得到14篇。通过仔细阅读全文,严格按照纳入及排除标准,再次排除文献7篇(研究对象未符合标准2篇,干预措施不符2篇,数据不全1篇,重复发表文献2篇),最终纳入7篇文献进行Meta分析[17-23],筛选流程见图1。其中6篇为随机对照研究[17-22],1篇为队列研究[23],共计1 256例病例,包括骨形态发生蛋白组793例,对照组463例。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。"
2.2.1 术后愈合率 6篇文献报道了骨愈合率[17-20,22-23]。异质性检验提示各研究间存在较高异质性(I2=59%,P=0.02),故采用随机效应模型。Meta分析结果显示,骨形态发生蛋白组与对照组愈合率比较差异无显著性意义[RR=1.11,95%CI(0.99,1.25),P=0.07],但可观察到骨形态发生蛋白具有利于骨折愈合的趋势,见图3。敏感性分析结果显示,分别单独剔除Govender(2002b)等[20]和Lyon(2013b)等[22]的研究后,异质性均有所减小(I2=45%和I2=42%)。其中,剔除Lyon(2013b)等[22]的研究后Meta分析结果发生改变[RR=1.14,95%CI(1.02,1.28),P=0.02]。分析原因可能是:①Lyon(2013b)等[22]的研究中患者骨折类型均为闭合性,骨缺损及软组织损伤程度较开放性轻,相比之下骨形态发生蛋白的成骨优势并不明显;②该研究采用的骨形态发生蛋白载体(磷酸钙基质)和其他文献(可吸收胶原海绵)报道的不同,载体的劣势导致骨形态发生蛋白的生物利用度较低;③该研究中骨形态发生蛋白的剂量(2.0 g/L)较高,使用高剂量的骨形态发生蛋白伴随着并发症增加的风险,一定程度上会对骨折愈合产生消极影响。"
考虑骨形态发生蛋白的剂量不同对结果的影响,故纳入其中3篇剂量为1.5 g/L的研究进行合并分析[18-20]。但Meta分析结果无明显改变,2组的愈合率比较差异无显著性意义[RR=1.19,95%CI(0.95,1.49),P=0.13]。 对3篇仅包含开放性骨折的研究进行Meta分析[17-18, 20],异质性检验提示存在不明显异质性(I2=27%,P=0.25),故采用固定效应模型。结果显示骨形态发生蛋白组的愈合率显著高于对照组[RR=1.16,95%CI(1.04,1.30),P=0.009],2组愈合率分别为64.4%(316/491)和58.5%(203/347),见图4。表明应用骨形态发生蛋白能够提高急性胫骨开放性骨折的愈合率。"
2.2.7 异位骨化及软组织钙化率 4篇文献提供了异位骨化及软组织钙化的具体数据[18-19,22-23]。各研究间无统计学异质性(I2=0%,P=0.46),故采用固定效应模型。Meta分析结果显示,骨形态发生蛋白组较对照组具有更高的异位骨化及软组织钙化率[RR=2.89,95%CI(1.40,5.95),P=0.004],2组发生率分别为13.8%(58/421)和3.8%(9/235),见图10。此外,Govender等[20]的研究结果表示,在标准护理中添加骨形态发生蛋白不会增加偏远部位局部软组织钙化或异位骨化的发生率。然而,该研究没有提供具体数据,故未能纳入此次Meta分析。 2.2.8 骨折愈合时间 4篇文献对骨折愈合时间进行了相关描述[18, 20,22-23],但由于缺乏详细数据,未能进行合并分析。GOVENDER等[20]的研究报道,1.5 g/L骨形态发生蛋白组骨折愈合时间明显短于对照组(P=0.002 2),其50%患者骨折愈合时间相比对照组缩短39 d;RISTINIEMI等[23]的研究中,骨形态发生蛋白组的愈合时间明显短于对照组(P=0.002),骨折愈合的患者在16周(P=0.039)和20周(P=0.022)均明显多于对照组;ARO等[18]的结果显示术后13周骨形态发生蛋白组的骨折愈合率高于对照组(60% vs. 48%),但未达到统计学差异(P=0.054 1);LYON等[22]的研究则表明两者在骨折愈合时间方面差异无显著性意义(P=0.476)。"
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