骨形态发生蛋白2，7治疗骨不连的效果评价

doi:10.3969/j.issn.2095-4344.2687

中国组织工程研究 ›› 2020, Vol. 24 ›› Issue (26): 4243-4250.doi: 10.3969/j.issn.2095-4344.2687

• 组织构建综述 tissue construction review • 上一篇下一篇

骨形态发生蛋白2，7治疗骨不连的效果评价

从凯¹，李善龙¹，王飞¹，程辉¹，李百通²，尚剑¹

¹哈尔滨医科大学附属第一医院骨一科，黑龙江省哈尔滨市 150000；²甘肃省中医院急诊骨科，甘肃省兰州市 730050

收稿日期:2019-10-12 修回日期:2019-10-19 接受日期:2019-12-06 出版日期:2020-09-18 发布日期:2020-09-03
通讯作者: 尚剑，博士，主任医师，哈尔滨医科大学附属第一医院骨一科，黑龙江省哈尔滨市 150000
作者简介:从凯，男，1991年生，河南省平舆县人，汉族，2020年于哈尔滨医科大学毕业，在读硕士。

Assessments of bone morphogenetic proteins 2 and 7 in treating nonunion

Cong Kai¹, Li Shanlong¹, Wang Fei¹, Cheng Hui¹, Li Baitong², Shang Jian¹

¹Department of Orthopaedics, the First Affiliated Hospital of Harbin Medical University, Harbin 150000, Heilongjiang Province, China; ²Department of Emergency Orthopedics, Gansu Hospital of Traditional Chinese Medicine, Lanzhou 730050, Gansu Province, China

Received:2019-10-12 Revised:2019-10-19 Accepted:2019-12-06 Online:2020-09-18 Published:2020-09-03
Contact: Shang Jian, MD, Chief physician, Department of Orthopaedics, the First Affiliated Hospital of Harbin Medical University, Harbin 150000, Heilongjiang Province, China
About author:Cong Kai, Master candidate, Department of Orthopaedics, the First Affiliated Hospital of Harbin Medical University, Harbin 150000, Heilongjiang Province, China

摘要/Abstract

摘要：

文题释义：

骨形态发生蛋白：具有成骨活性，可通过不同的信号通路促进骨髓间充质干细胞的成骨分化。

骨不连：骨损伤和骨折后超过9个月，连续超过3个月观察未见进一步愈合的倾向。

背景：自体骨移植辅以坚强固定被认为是治疗骨不连的金标准，目前临床上使用骨形态发生蛋白2，7对骨不连进行治疗的案例较多。

目的：从基因水平描述骨形态发生蛋白的成骨通路，对临床上骨形态发生蛋白治疗骨不连的案例进行分析，同时对比骨形态发生蛋白2，7对骨不连的治疗效果，并对二者效果进行评价及分析。

方法：由第一作者用计算机检索中国期刊全文数据库、万方数据库和PubMed数据库，中文检索词为“骨形态发生蛋白、骨不连、信号通路、外固定架、内固定、植骨、感染性骨不连、骨缺损、成骨细胞、骨分化”，英文检索词为“BMP，nonunion，pathway，External fixator，ORIF，bone graft，infected nonunion，bone defect，osteoblast，osteoporosis”，最终纳入文献59篇。

结果与结论：①通过对文献的分析，认为骨形态发生蛋白的基因水平通路可以为其临床应用提供治疗思路；②在对于骨不连的治疗上，骨形态发生蛋白2，7是有效的，但目前缺乏使用骨形态发生蛋白治疗骨不连的规范及标准，例如使用量及适应证；③从总体治疗效果及对感染性骨不连的治疗效果两方面，对比骨形态发生蛋白2，7，认为骨形态发生蛋白2的效果优于骨形态发生蛋白7，尤其是在感染性骨不连的治疗中。

ORCID: 0000-0002-6610-7252(从凯)

中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程

关键词: 骨形态发生蛋白, 骨不连, 信号通路, 骨形态发生蛋白2, 骨形态发生蛋白7, 植骨, 感染性骨不连, 骨缺损, 成骨细胞, 骨分化

Abstract:

BACKGROUND: Autologous bone transplantation combined with strong fixation is considered as the gold standard for the treatment of nonunion. At present, there are many cases in which bone nonunion is treated with bone morphogenetic proteins 2 and 7.

OBJECTIVE: To describe the osteogenic pathway of bone morphogenetic proteins at the gene level,

summarize the clinical cases of nonunion treated with bone morphogenetic protein, and compare the therapeutic effects of bone morphogenetic proteins 2 and 7 on nonunion, followed by evaluation and analysis.

METHODS: The first author used a computer to search the full-text database of Chinese journals, WanFang database and PubMed database. The key words were “BMP, nonunion, pathway, external fixator, ORIF, bone graft, infected nonunion, bone defect, osteoblast, osteoporosis " and 59 articles were finally included in the result analysis.

RESULTS AND CONCLUSION: Literature review indicates that the gene-level pathway of bone morphogenetic protein can provide therapeutic ideas in clinical practice. In the treatment of bone nonunion, bone morphogenetic proteins 2 and 7 are effective, but there are yet no specifications and standards for the use of bone morphogenetic proteins, such as usage amount and indications. From the overall treatment effect and the treatment effect on infected bone nonunion, we compare the use of bone morphogenetic proteins 2 and 7. The effect of bone morphogenetic protein 2 is better than that of bone morphogenetic protein 7, especially in the treatment of infected nonunion.

Key words: bone morphogenetic protein, nonunion, signaling pathway, bone morphogenetic protein 2, bone morphogenetic protein 7, bone graft, infected nonunion, bone defect, osteoblasts, osteogenic differentiation

中图分类号:

从凯, 李善龙, 王飞, 程辉, 李百通, 尚剑. 骨形态发生蛋白2，7治疗骨不连的效果评价[J]. 中国组织工程研究, 2020, 24(26): 4243-4250.

Cong Kai, Li Shanlong, Wang Fei, Cheng Hui, Li Baitong, Shang Jian.

Assessments of bone morphogenetic proteins 2 and 7 in treating nonunion [J]. Chinese Journal of Tissue Engineering Research, 2020, 24(26): 4243-4250.

图/表（结果） 2

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引言

材料方法

讨论

通过上述骨形态发生蛋白7及骨形态发生蛋白2在临床骨不连的治疗方案的分析，他们总体的治疗效果是不容置疑的，但同时文章发现，每个治疗者在对骨形态发生蛋白的治疗剂量以及固定方式的选择上是不同的，即便是同类型骨折；对于是否采用自体骨移植、同种异体骨还是骨替代物的选择也是不同的。文献中对于儿童及老年人的治疗方案，以及骨盆骨不连的治疗，也为临床工作提供了指导。骨形态发生蛋白2及骨形态发生蛋白7的对比中发现，骨形态发生蛋白2对于感染性骨不连的治疗也是有指导意义的。但有一点不容忽视的问题，骨形态发生蛋白在骨不连方面的治疗在FDA的药物说明上属于标签外的使用方法，随着骨形态发生蛋白在骨不连治疗上的发展，文章认为标签外的使用是未尝不可的。至于是否能将骨形态发生蛋白结合骨移植作为骨不连的首选治疗方案，还需要判断该骨不连是否为顽固性骨不连，而顽固性骨不连的前期判定措施在临床上是一项空白。

文章总结骨形态发生蛋白的通路研究还发现，骨形态发生蛋白可以在体内对多种细胞产生不同的效应，并参与除了骨骼系统外的多种生物学活动，包括消化、胚胎形成、器官生成、血管生成及血管完整性及性生殖等相关过程^[52]。仅仅在骨不连的治疗上，上述所查询的文献就报道有诸如异位成骨、炎性反应、软组织肿胀、神经炎、急性间隔肿胀乃至癌症的并发症等^[52]。很多机制文章尚未能对之加以了解及阐述，加之骨形态发生蛋白的使用浓度比正常生理浓度要高100万倍^[54]，而临床上关于其剂量尚未有统一的标准，从这方面来讲，需要更多的实验及临床研究来为骨形态发生蛋白用于骨不连的治疗提供标准，从而在更少并发症的前提下获得对骨不连更好的治疗效果。

骨形态发生蛋白的临床应用任重而道远，目前，除了应用到常规的以水凝胶形式，高分子及纳米材料的发展为其应用提供了理想的载体材料，这是未来的研究方向及热点，目前已被搭载的载体有很多^[58-59]，诸如磷酸钙陶瓷，其对蛋白质具有高亲和力，可方便对骨形态发生蛋白进行载药；类似的材料还有磷酸钙骨水泥，具有生物相容性高，易于成型等优点；生物活型玻璃也被应用到载体材料中；需要指出的是纳米材料的应用，他可以为骨形态发生蛋白提供缓释特性，有些材料比如PNIPAAM同时具有温敏特性；目前关于复合材料搭载骨形态发生蛋白是一个热点，即将不同的材料按不同比例混合形成具有较好生物性能的新型材料，但需要更多的实验来验证这些材料的安全性及有效性，为临床的应用提供充分的证据。

总之，文章查阅历年文献，最后得出骨形态发生蛋白治疗骨不连，尤其是顽固性骨不连的效果是确切的，针对于萎缩性骨不连，其效果是优于单纯植骨固定的。针对儿童先天性假关节的治疗，以及老年患者萎缩性骨不连的治疗具有一定的指导意义。同时，骨形态发生蛋白2的效果是优于骨形态发生蛋白7，尤其是在针对于感染性骨不连的治疗中。但是需要注意的是，文献中的骨形态发生蛋白用于骨不连治疗的使用均是标签外的，其用法、用量以及适应证均没有统一的规范，需要更多的数据为其规范化提供支撑。

中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程

骨形态发生蛋白2，7治疗骨不连的效果评价

Assessments of bone morphogenetic proteins 2 and 7 in treating nonunion

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