骨转化标志物评价富血小板血浆辅助治疗胫骨骨折手术后的不愈合

Adjuvant treatment of nonunion of tibial fractures with platelet-rich plasma evaluated by bone turnover markers

背景:富血小板血浆凭借其超强的促进愈合作用在临床上逐渐得到应用,但目前缺少高质量临床对比研究来明确其对骨折不愈合的作用及作用机制。目的:比较富血小板血浆联合手术治疗与单纯手术治疗胫骨干骨折术后不愈合的效果,分析相应骨折修复实验室指标。方法:收集2017年1月至2020年1月青岛大学附属威海市中心医院连续收入的胫骨干骨折术后不愈合患者30例,根据二次手术方式分为富血小板血浆联合手术组16例(术后每隔1周注射自体富血小板血浆1次,共注射3次)和单纯手术组14例。手术当日(术前)及术后2,4,8,12周时抽取两组患者血液标本,检测骨钙素、骨性碱性磷酸酶及β-Ⅰ型胶原羧基末端肽水平;观察两组患者手术切口愈合情况;术后3,6,9个月时对两组患者进行骨痂和骨折线影像学评分及目测类比评分,记录两组患者骨折临床愈合及骨性愈合时间。研究方案经青岛大学附属威海市中心医院伦理委员会批准(2016-伦审-07)。结果与结论:①两组患者术后血清骨钙素、骨性碱性磷酸酶及β-Ⅰ型胶原羧基末端肽水平均呈升高趋势,富血小板血浆联合手术组患者术后2,4周的骨钙素水平高于单纯手术组(P<0.05),术后2,4,8周的骨性碱性磷酸酶高于单纯手术组(P<0.05),术后的β-Ⅰ型胶原羧基末端肽始终高于单纯手术组(P<0.05);②富血小板血浆联合手术组、单纯手术组患者的切口甲级愈合率分别为88%,64%;富血小板血浆联合手术组患者的骨折临床愈合时间及骨性愈合时间均短于单纯手术组(P<0.05);③富血小板血浆联合手术组患者术后3,6,9个月的骨痂和骨折线影像学评分均高于单纯手术组(P<0.05),目测类比评分均低于单纯手术组(P<0.05);④结果表明,富血小板血浆联合手术治疗胫骨干骨折术后不愈合效果要优于单纯手术治疗,可提高患者血清骨钙素、骨性碱性磷酸酶及β-Ⅰ型胶原羧基末端肽水平,有助于富血小板血浆治疗骨折不愈合的机制研究及临床预后判断。

BACKGROUND:Due to the super-healing effect,platelet-rich plasma is gradually used in the clinic.Nevertheless,high-quality clinical comparative studies are currently absent to identify its effect on fracture nonunion and its action mechanism.OBJECTIVE:To compare the effects between platelet-rich plasma combined with surgery and surgery alone in the treatment of nonunion after tibial shaft fractures,and to analyze the corresponding laboratory indicators of fracture repair.METHODS:Thirty patients with nonunion of tibial shaft fractures treated in Weihai Central Hospital Affiliated to Qingdao University from January 2017 to January 2020 were enrolled in this study.According to the second operation method,these patients were divided into platelet-rich plasma combined surgery group(n=16;autologous platelet-rich plasma injection once every other week for three injections)and operation group(n=14).Blood samples were taken from patients of the two groups to detect the levels of osteocalcin,bone alkaline phosphatase andβ-I collagen carboxyl terminal peptide on the day of surgery(before surgery)and at 2,4,8,and 12 weeks after surgery.The surgical incision healing of the patients was observed between the two groups.At 3,6,and 9 months after surgery,the callus and fracture line imaging scores and visual analogue scale scores were analyzed in the two groups,and the clinical healing and bone healing time were recorded in the two groups.The protocol was approved by the Ethics Committee of Weihai Central Hospital Affiliated to Qingdao University(approval No.2016-Lunshen-07).RESULTS AND CONCLUSION:(1)The levels of serum osteocalcin,bone alkaline phosphatase andβ-I collagen carboxyl terminal peptide increased in the two groups after surgery.The osteocalcin level in the platelet-rich plasma combined surgery group was higher than that in the operation group at 2 and 4 weeks after surgery(P<0.05).Bone alkaline phosphatase was higher in the platelet-rich plasma combined surgery group than that in the operation group at 2,4,and 8 weeks after surgery(P<0.05).Theβ-I collagen carboxyl terminal peptide level was higher in the platelet-rich plasma combined surgery group than that in the operation group after surgery(P<0.05).(2)The grade A healing rates of incisions were 88%and 64%in the platelet-rich plasma combined surgery group and the operation group,respectively.The clinical fracture healing time and bone healing time were shorter in the platelet-rich plasma combined surgery group than those in the operation group(P<0.05).(3)The imaging scores of callus and fracture line were higher in the platelet-rich plasma combined surgery group than those of the operation group at 3,6,and 9 months after surgery(P<0.05).Visual analogue scale scores were lower in the platelet-rich plasma combined surgery group than those of the operation group(P<0.05).(4)These findings indicate that the effect of platelet-rich plasma combined with surgery for nonunion of tibial shaft fractures is better than that of surgery alone.Their combination can increase the serum levels of osteocalcin,bone alkaline phosphatase,andβ-I collagen carboxyl terminal peptide,and is helpful to investigate the mechanism of platelet-rich plasma for fracture nonunion and to judge the clinical prognosis.