脑外伤与四肢骨折患者血清BMP-2与异位骨化的临床对照试验

Comparative study of serum levels of BMP-2 and heterotopic ossification in traumatic brain injury and fractures patients

目的:探讨脑外伤和四肢骨折患者血清骨成型蛋白-2(bone morphogenetic proteins2,BMP2)在异位骨化发生中的作用,为异位骨化的临床预防提供一定的理论依据。方法:选择2007年12月至2009年1月入院的外伤患者145例,包括原发性闭合性脑损伤96例,原发性开放性脑损伤1例,尺桡骨骨折29处,肱骨骨折11处,胫腓骨骨折32处,股骨骨折27处。按骨折类型分为A、B、C3组:A组(单纯脑外伤组)57例,男37例,女20例;年龄29～61岁,平均(43.91±11.09)岁;病程13～67d,平均(18.96±10.46)d。B组(单纯四肢骨折组)48例,男25例,女23例;年龄31～54岁,平均(41.73±8.41)岁;病程6～48d,平均(16.02±8.71)d。C组(脑外伤合并四肢骨折组)40例,男23例,女17例;年龄30～60岁,平均(45.87±14.15)岁;病程18～76d,平均(21.28±13.02)d。对移位不明显的31处四肢骨折采用牵引、石膏固定或夹板固定;对骨折移位明显或开放性的68处四肢骨折采用髓内钉内固定或钢板螺钉内固定。对63例颅脑损伤患者立即行开颅手术,其余34例行止血、降脑压、改善脑血循环等综合治疗。按14～16个月后髋、肩、肘、膝关节部位X线平扫是否存在异位骨化分为D、E2组:D组(可见异位骨化组)17例,男11例,女6例;年龄29～55岁,平均(46.88±7.13)岁;病程6～30d,平均(20.18±9.78)d。E组(未见异位骨化组)128例,男74例,女54例;年龄33～61岁,平均(43.31±12.94)岁;病程15～76d,平均(18.42±11.58)d。另设F组(体检人群)49例作为对照,男29例,女20例;年龄31～60岁,平均(43.50±14.40)岁。145例在骨折发生后0.5、3、15、30d抽取外周静脉血,用酶联免疫吸附法检测其血清中BMP2的含量,并用SPSS13.0统计学软件进行统计处理。结果:单纯脑外伤患者(21.05%,12/57)和单纯四肢骨折患者(4.17%,2/48)的异位骨化发生率差异有统计学意义(χ2=5.05,P<0.05)。0.5、3、15d时A、B组血清BMP2水平差异均有统计学意义。0.5、3、15、30d时D、E组血清BMP2水平差异均有统计学意义。A、B、C、D、E组各时间点血清BMP2水平均高于对照组血清BMP2水平(51.30±23.41)ng/L(P<0.01)。结论:单纯脑外伤患者血清高水平BMP2是发生异位骨化的因素之一,其15d的浓度可能是预防异位骨化的观察指标。

Objective：To investigate the relationship between serum level of bone morphogenetic proteins-2 （BMP-2） and heterotopic ossification （HO） in traumatic brain injury （TBI） and fractures patients,providing the theoretical evidence for the clinical prevention of HO. Methods：From December 2007 to January 2009,145 with trama patients were selected. There were 96 closed primary traumatic brain injury patients, 1 penetrating primary traumatic brain injury,29 fractures of the radius and ulna, 11 fractures of the humerus,32 fractures of the tibia and fibula,27 fractures of the femur. All patients were divided into three groups （i.e., group A, group B and group C ） by the type of fracture. Fifty-seven patients in group A （TBI only ）, including 37 males and 20 females,ranged in the age from 29 to 61 years,with an average age of （43.91 ±11.09） years. The disease course was from 13 to 67 d ,with an average duration of （18.96±10.46） d. Forty-eight patients in group B （fractures only） ,25 males and 23 females,ranged in age from 31 to 54 years,with an average age of （41.73±8.41） years. The disease course was from 6 to 48 d,with an average duration of （16.02±8.71） d. Forty patients in group C （TBI combined with extremities fractures）, including 23 males and 17 females, ranged in age from 30 to 60 years,with an average age of （45.87± 14.15 ） years. The disease course was from 18 to 76 d,with an average of （21.28±13.02） d. Thirty-one extremities fractures with no significant separations or displacements of fragments were treated with traction reductions,east immobilization or splint fixations. Sixtyeight fractures with significant separations and displacements of fragments were treated with intramedullary nail fixations or screw internal fixations. Sixty-three TBI patients were treated with open-skull surgeries immediately while 34 TBI patients were treated with stanching bleeding, reducing intracranial pressure and improving cerebral blood circulation. All patients were also divided into two groups （group D and group E ） according to the 14-to 16-month follow-up X-ray film results. Seventeen patients in group D （HO had been found） ,including 11 males and 6 females,ranged in age from 29 to 55 years old,with an average age of （46.88±7.13 ） years. The disease course was from 6 to 30 d,with an average of （20.18±9.78） d. All 128 patients in group E （HO had been not found） ,including 74 males and 54 females,ranged in age from 33 to 61 years,with an average age of （43.31± 12.94） years. The disease course was from 15 to 76 d, with an average of （18.42± 11.58 ） d. The 49 subjects in group F （normal controls）, 29 males and 20 females, ranged in age from 31 to 60 years, average （43.50± 14.40） years. Peripheral blood samples were taken for the determination of BMP-2 in blood serum on 0.5,3,15 d and 30 d after fractures by enzyme-linked immunosorbent assay （ELISA）. Analysis of variance and least significant difference test were done with the help of SPSS 13.0 statistic software. Results：The incidence rates of HO between the TBI only patients （21.05%, 12/57） and the fractures only patients （4.17%, 2/48 ） were significant different （x2=5.05, P〈0.05 ）. Serum levels of BMP-2 at 0.5,3 d and 15 d between group A and group B were significant different. Serum levels of BMP-2 at 0.5,3,15 d and 30 d between group D and group E were significant different. Serum levels of BMP-2 at each time in each group were higher than the control group （51.30±23.41 ng/L） （P〈0.01）. Conclusion： High serum levels of BMP-2 in TBI only group is one of factors in causing HO. Serum level of BMP-2 at 15 d since fractures may be the obvervational index of HO prevention.