富血小板血浆联合体外冲击波治疗骨不连的临床研究

A clinical study of injection of platelet-rich plasma combined with extracorporeal shock wave therapy for treatment of nonunion of fractures

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。

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 other fractures(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-βin 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.