[1]姜苗苗,谭勇海,金鑫,等.富血小板血浆联合体外冲击波治疗骨不连的临床研究[J].中医正骨,2020,32(02):30-35.
　JIANG Miaomiao,TAN Yonghai,JIN Xin,et al.A clinical study of injection of platelet-rich plasma combined with extracorporeal shock wave therapy for treatment of nonunion of fractures[J].The Journal of Traditional Chinese Orthopedics and Traumatology,2020,32(02):30-35.
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富血小板血浆联合体外冲击波治疗骨不连的临床研究()
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《中医正骨》[ISSN:1001-6015/CN:41-1162/R]

卷:
第32卷
期数:
2020年02期
页码:
30-35
栏目:
临床研究
出版日期:
2020-02-20

文章信息/Info

Title:
A clinical study of injection of platelet-rich plasma combined with extracorporeal shock wave therapy for treatment of nonunion of fractures
作者:
姜苗苗; 谭勇海; 金鑫; 鞠昌军; 姜红江
(山东省文登整骨医院,山东 威海 264400)
Author(s):
JIANG Miaomiao; TAN Yonghai; JIN Xin; JU Changjun; JIANG Hongjiang
The Wendeng Osteopath Hospital,Weihai 264400,Shandong,China
关键词:
骨折; 不愈合;  富血小板血浆;  高能量冲击波;  临床试验
Keywords:
fractures; ununited;  platelet-rich plasma;  high-energy shock waves;  clinical trial
摘要:
目的:探讨富血小板血浆联合体外冲击波治疗骨不连的临床疗效和安全性。方法:骨不连患者58例,男42例、女16例; 年龄20～45岁,中位数34.5岁。胫腓骨骨折24例,股骨干骨折15例,股骨颈骨折8例,尺桡骨骨折7例,其他部位骨折4例。均符合美国食品药品监督管理局制定的骨不连诊断标准,且骨折端间隙<5 mm,骨痂间无骨小梁形成,无骨折端短缩、成角及移位。随机分为联合治疗组和体外冲击波组,每组29例。联合治疗组制备患者自体富血小板血浆,并检测血浆中血管内皮生长因子(vascular endothelial growth factor,VEGF)和转化生长因子-β(transforming growth factor-β,TGF-β)的含量; 在C形臂X线机透视下定位骨折端,注入富血小板血浆,注射完毕后进行冲击波治疗。体外冲击波组单纯进行体外冲击波治疗。治疗均由同一组医师完成,每隔4 d治疗1次,共治疗3次。分别于治疗前和治疗结束后2个月、3个月、4个月、6个月、8个月,采用骨痂和骨折线影像学评分标准在X线片上评价骨折愈合情况。观察并发症发生情况。结果:①细胞生长因子检测结果。制备的患者自体富血小板血浆中,细胞生长因子VEGF和TGF-β的含量分别为(583.87±23.51)pg·mL-1、(195.73±26.08)pg·mL-1。②疗效和安全性评价结果。2组患者均获随访,随访时间2～8个月,中位数4个月。治疗前后不同时间点,患者骨痂影像学评分的差异有统计学意义,即存在时间效应(F=35.696,P=0.000); 2组患者骨痂影像学评分组间总体比较,差异无统计学意义,即不存在分组效应(F=9.872,P=0.518); 时间因素和分组因素存在交互效应(F=56.877,P=0.000)。治疗前,2组患者骨痂影像学评分比较,差异无统计学意义[(1.77±0.63)分,(1.79±0.65)分; t=0.187,P=0.245]; 治疗结束后2个月、3个月、4个月、6个月及8个月,联合治疗组骨痂影像学评分均高于体外冲击波组[(2.45±0.67)分,(1.95±0.45)分,t=0.847,P=0.000;(3.27±0.55)分,(2.14±0.15)分,t=2.578,P=0.000;(7.83±0.88)分,(3.87±0.54)分,t=6.087,P=0.000;(5.87±0.38)分,(3.75±0.65)分,t=3.856,P=0.000;(4.67±0.85)分,(3.25±0.88)分,t=1.879,P=0.000]。治疗前后不同时间点,患者骨折线影像学评分比较,差异有统计学意义,即存在时间效应(F=42.876,P=0.000); 2组患者骨折线影像学评分组间总体比较,差异无统计学意义,即不存在分组效应(F=12.631,P=0.678); 时间因素和分组因素存在交互效应(F=67.541,P=0.000)。治疗前,2组患者骨折线影像学评分的组间差异无统计学意义[(1.26±0.67)分,(1.28±0.68)分; t=1.587,P=0.342]; 治疗结束后2个月、3个月、4个月、6个月及8个月,联合治疗组骨折线影像学评分均高于体外冲击波组[(2.45±0.87)分,(1.98±0.78)分,t=2.876,P=0.000;(3.42±0.35)分,(2.12±0.57)分,t=5.687,P=0.000;(6.12±0.87)分,(3.45±0.64)分,t=9.864,P=0.000;(5.62±0.42)分,(3.12±0.85)分,t=6.874,P=0.000;(4.21±0.75)分,(2.85±0.64)分,t=3.587,P=0.000]。2组患者均无血管、神经损伤等并发症发生。结论:采用富血小板血浆联合体外冲击波治疗骨不连,可促进骨折愈合,并发症少,疗效优于单纯体外冲击波治疗。
Abstract:
Objective:To explore the clinical curative effects and safety of injection of platelet-rich plasma(PRP)combined with extracorporeal shock wave(ESW)therapy for treatment of nonunion of fractures.Methods:Fifty-eight patients with nonunion of fractures were enrolled in the study and they consisted of 42 males and 16 females and ranged in age from 20 to 45 years(Median=34.5 yrs).The fractures belonged to tibiofibular fractures(24),femoral shaft fractures(15),femoral neck fractures(8),ulna and radius fractures(7)and otherfractures(4).All patients met the diagnostic criteria of nonunion of fractures established by U.S. Food and Drug Administration.The interspace between broken ends of fractured bone was<5 mm and no bone trabeculas were found between bony calluses.Meanwhile,no shortening,angulation and displacement of broken ends of fractured bone were found.The patients were randomly divided into combination therapy group and ESW therapy group,29 cases in each group.The venous blood was drawn from patients in combination therapy group and was made into autologous PRP,and the contents of vascular endothelial growth factor(VEGF)and transforming growth factor-β(TGF-β)in autologous PRP were detected.The autologous PRP were injected into the broken ends of fractured bone which were fixed the position using C-arm X-ray machine and then ESW therapy was performed on patients in combination therapy group.The patients in ESW therapy group were merely treated with ESW therapy.The treatment were performed on patients in the 2 groups by the same group of surgeons for consecutive 3 times with a 4-day rest-insertion between times.The fracture healing was evaluated using X-ray films according to bony callus and fracture line imageological scoring standard before the treatment and at 2,3,4,6 and 8 months after the end of the treatment respectively,and the complication incidences were observed.Results:The contents of VEGF and TGF-β in pre-prepared autologous PRP were 583.87+/-23.51 and 195.73+/-26.08 pg/mL respectively.All patients in the 2 groups were followed up for 2-8 months with a median of 4 months.There was statistical difference in bony callus imageological scores between different timepoints before and after the treatment,in other words,there was time effect(F=35.696,P=0.000).There was no statistical difference in bony callus imageological scores between the 2 groups in general,in other words,there was no group effect(F=9.872,P=0.518).There was interaction between time factor and group factor(F=56.877,P=0.000).There was no statistical difference in bony callus imageological scores between the 2 groups before the treatment(1.77+/-0.63 vs 1.79+/-0.65 points,t=0.187,P=0.245).The bony callus imageological scores were higher in combination therapy group compared to ESW therapy group at 2,3,4,6 and 8 months after the end of the treatment respectively(2.45+/-0.67 vs 1.95+/-0.45 points,t=0.847,P=0.000; 3.27+/-0.55 vs 2.14+/-0.15 points,t=2.578,P=0.000; 7.83+/-0.88 vs 3.87+/-0.54 points,t=6.087,P=0.000; 5.87+/-0.38 vs 3.75+/-0.65 points,t=3.856,P=0.000; 4.67+/-0.85 vs 3.25+/-0.88 points,t=1.879,P=0.000).There was statistical difference in fracture line imageological scores between different timepoints before and after the treatment,in other words,there was time effect(F=42.876,P=0.000).There was no statistical difference in fracture line imageological scores between the 2 groups in general,in other words,there was no group effect(F=12.631,P=0.678).There was interaction between time factor and group factor(F=67.541,P=0.000).There was no statistical difference in fracture line imageological scores between the 2 groups before the treatment(1.26+/-0.67 vs 1.28+/-0.68 points,t=1.587,P=0.342).The fracture line imageological scores were higher in combination therapy group compared to ESW therapy group at 2,3,4,6 and 8 months after the end of the treatment respectively(2.45+/-0.87 vs 1.98+/-0.78 points,t=2.876,P=0.000; 3.42+/-0.35 vs 2.12+/-0.57 points,t=5.687,P=0.000; 6.12+/-0.87 vs 3.45+/-0.64 points,t=9.864,P=0.000; 5.62+/-0.42 vs 3.12+/-0.85 points,t=6.874,P=0.000; 4.21+/-0.75 vs 2.85+/-0.64 points,t=3.587,P=0.000).No complications such as blood vessel injuries and nerve injuries were found in both of the 2 groups.Conclusion:PRP combined with ESW therapy can promote fracture healing in treatment of nonunion of fractures,and it has less complications,moreover,it surpasses the monotherapy of ESW therapy in clinical curative effects.

参考文献/References:

[1] 陈剑,袁文,宋滇文.富血小板血浆在骨愈合治疗中的作用[J].中国组织工程研究与临床康复,2011,15(41):7755-7758.
[2] 谭勇海,姜苗苗,李佳林,等.不同方法制备的富含血小板血浆裂解液对成人骨髓间充质干细胞增殖、成骨的影响[J].中国中医骨伤科杂志,2013,21(2):5-7.
[3] RODRIGUEZ-MERCHAN E C,FORRIOL F.Nonunion:general principles and experimental data[J].Clin Orthop Relat Res,2004(419):4-12.
[4] 孟俊飞.医学影像学[M].北京:高等教育出版社,2004:245.
[5] 洪帆,谢加兵,丁国正.内固定植入物与外固定支架修复胫骨骨折骨不连的策略及辅助治疗[J].中国组织工程研究,2016,20(26):3946-3952.
[6] 罗华,薛锋,苏永蔚,等.两种方法治疗股骨干髓内钉固定后骨不连的荟萃分析[J].中国矫形外科杂志,2019,27(6):525-529.
[7] 李智斌,杨利学,朱伟,等.附加钢板联合骨复生治疗股骨干骨折术后骨不连31例[J].中国中医骨伤科杂志,2019,27(8):40-43.
[8] 帕尔哈提·瓦哈甫,赵博,艾科热木·吾普尔,等.优化穿针组合式外固定架治疗股骨远端骨不连的临床疗效[J].中华骨与关节外科杂志,2019,12(3):186-190.
[9] 沈哲源,田书委,赵玉静,等.间充质干细胞移植治疗骨不连研究现状[J].中国矫形外科杂志,2018,26(5):432-435. 中医正骨2020年2月第32卷第2期 J Trad Chin Orthop Trauma,2020,Vol.32,No.2(总115) (总116)中医正骨2020年2月第32卷第2期 J Trad Chin Orthop Trauma,2020,Vol.32,No.2
[10] 王小鹤,刘彬,程继强,等.股骨干骨折术后无菌性骨不连的内固定手术方案研究进展[J].中医正骨,2018,30(8):46-49.
[11] 曹曦,崔伟,路通.胫骨骨折骨不连的原因分析及治疗进展[J].中医正骨,2017,29(8):50-52.
[12] ANITUA E.Plasma rich in growth factors:preliminary results of use in the preparation of future sites for implants[J].Int J Oral Maxillofac Implants,1999,14(4):529-535.
[13] SONNLEITNER D,HUEMER P,SULLIVAN D Y.A simplified technique for producing platelet-rich plasma and platelet concentrate for intraoral bone grafting techniques:a technical note[J].Int J Oral Maxillofac Implants,2000,15(6):879-882.
[14] AGHALOO T L,MOY P K,FREYMILLER E G.Investigation of platelet-rich plasma in rabbit cranial defects:a pilot study[J].J Oral Maxillofac Surg,2002,60(10):1176-1181.
[15] SHU D Y,HUTCHEON A E K,ZIESKE J D,et al.Epidermal growth factor stimulates transforming growth factor-beta receptor type Ⅱ expression in corneal epithelial cells[J].Sci Rep,2019,9(1):8079.
[16] GUPTA V,SHUKLA S,HUSAIN N,et al.A comparative study of cell block versus biopsy for detection of epidermal growth factor receptor mutations and anaplastic lymphoma kinase rearrangement in adenocarcinoma lung[J].J Cytol,2019,36(1):13-17.
[17] KHANDELWAL A R,KENT B,HILLARY S,et al.Fibroblast growth factor receptor promotes progression of cutaneous squamous cell carcinoma[J].Mol Carcinog,2019,58(10):1715-1725.
[18] 沈保磊,刘国浚,王耀生,等.体外冲击波治疗骨不连与骨折延迟愈合的应用进展[J].中国现代药物应用,2015,9(22):273-274.
[19] 陈波杰,曾广轩,钱锐,等.体外冲击波结合富血小板血浆治疗四肢骨折骨不连的临床观察[J].广东医学,2019,40(10):1480-1482.
[20] 李卫,高原,张守相,等.体外冲击波疗法治疗骨不连现状和思考[J].医学与哲学(B),2018,39(9):15-17.
[21] 王华,周才胜,谭虎成.研究不同时间体外冲击波疗法治疗骨不连的临床疗效[J].中外医疗,2018,37(26):23-25.
[22] 戴传强,张耀,张友树.体外冲击波(ESW)治疗骨不连的临床效果观察[J].临床医药文献电子杂志,2018,5(72):32-33.
[23] 全迪,任玉琦,王晓添.评价体外冲击波联合增强型纤维蛋白胶负载骨生长因子治疗骨不连的临床疗效[J].中国实用医药,2018,13(18):197-198.
[24] 黄晶焕,李晓林.体外冲击波疗法治疗骨不连研究进展[J].国际骨科学杂志,2018,39(1):17-20.
[25] 赵子星,李宏宇,席立成,等.体外冲击波疗法联合仙桃草口服用于兔桡骨骨不连临床效果观察[J].山东医药,2016,56(36):31-33.
[26] CHEN H S,CHEN L M,HUANG T W.Treatment of painful heel syndrome with shock waves[J].Clin Orthop Relat Res,2001,(387):41-46.
[27] MCCLURE S R,VAN SICKLE D,WHITE M R.Effects of extracorporeal shock wave therapy on bone[J].Vet Surg,2004,33(1):40-48.
[28] FRAIRIA R,BERTA L.Biological effects of extracorporeal shock waves on fibroblasts.A review[J].Muscles Ligaments Tendons J,2012,1(4):138-147.
[29] WANG C J,HUANG K E,SUN Y C,et al.VEGF modulates angiogenesis and osteogenesis in shockwave-promoted fracture healing in rabbits[J].J Surg Res,2011,171(1):114-119.
[30] VULPIANI M C,VETRANO M,CONFORTI F,et al.Effects of extracorporeal shock wave therapy on fracture nonunions[J].Am J Orthop(Belle Mead NJ),2012,41(9):E122-E127.

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备注/Memo

备注/Memo:
(收稿日期:2019-07-08 本文编辑:杨雅)基金项目:国家中医药管理局全国名老中医药专家传承工作室建设项目(国中医药人教函[2018]134号); 山东省科技发展计划项目(2014GSF118042); 威海市科技发展计划项目(2014GNS044、2017GNS013) 通讯作者:姜红江 E-mail:boneman@163.com
更新日期/Last Update: 2020-02-15