血清骨形成蛋白-4水平与异位骨化的关系研究

Study on the relationship between serum bone morphogenetic protein-4 levels and heterotopic ossification

目的:探讨血清骨形成蛋白-4水平与异位骨化发生的关系,为异位骨化的临床预防提供相应的理论依据。方法:选择2007年12月至2009年1月入院的外伤患者145例,按创伤类型分为3组:单纯脑外伤患者57例,纳入A组;单纯四肢骨折患者48例,纳入B组;脑外伤合并四肢骨折患者40例,纳入C组。入院后根据患者创伤类型予以治疗,并于伤后0.5 d、3 d、15 d、30 d经肘静脉采血测定患者血清骨形成蛋白-4含量。治疗后14～16个月随访时对患者肩、肘、髋、膝关节进行X线检查,然后按患者是否出现异位骨化分为2组:发生异位骨化者纳入Ⅰ组,未发生异位骨化者纳入Ⅱ组。比较A、B、C组患者的异位骨化发生情况,并对各测量时间点的血清骨形成蛋白-4含量进行分析。结果:①异位骨化发生情况。145例患者中发生异位骨化者17例(Ⅰ组),未发生异位骨化者128例(Ⅱ组);A、B、C组患者异位骨化发生率比较,差异有统计学意义(χ2=8.131,P=0.017),进一步两两比较(调整检验水准:a'=0.017):A组异位骨化率大于B组(χ2=6.430,P=0.011),其余各组间比较,差异无统计学意义(A组与C组比较:χ2=3.303,P=0.069;B组与C组比较:χ2=0.044,P=0.834)。②A、B、C组患者血清骨形成蛋白-4含量。不同时间点血清骨形成蛋白-4含量不同(F=41.753,P=0.000):A组0.5 d时含量与3 d时含量比较,差异无统计学意义(t=-0.479,P=0.633),15 d时含量高于3 d和30 d时含量(t=7.134,P=0.000;t=7.338,P=0.000);B组各时间点血清骨形成蛋白-4含量比较,差异无统计学意义(F=0.510,P=0.678);C组0.5 d时含量与3 d时含量比较,差异无统计学意义(t=-0.767,P=0.446),15 d时含量大于3 d和30 d时含量(t=5.725,P=0.000;t=4.326,P=0.000)。3组间血清骨形成蛋白-4含量总体有差别(F=122.299,P=0.000),进一步比较显示:0.5 d时A组含量大于B组和C组(t=5.391,P=0.000;t=5.567,P=0.000);3 d时A组含量大于B组和C组(t=4.678,P=0.000;t=3.848,P=0.000);15 d时A组含量大于B组和C组(t=12.007,P=0.000;t=6.561,P=0.000),B组含量小于C组(t=-7.591,P=0.000);30 d时A组含量大于B组和C组(t=7.094,P=0.000;t=3.581,P=0.000;),B组含量小于C组(t=-3.753,P=0.000)。时间和分组因素存在交互作用(F=18.404,P=0.000)。③Ⅰ、Ⅱ组患者血清骨形成蛋白-4含量。不同时间点血清骨形成蛋白-4含量不同(F=40.910,P=0.000)。Ⅰ组0.5 d时含量与3 d时含量比较,差异无统计学意义(t=-0.335,P=0.740),15 d时含量大于3 d和30 d时含量(t=4.586,P=0.000;t=3.796,P=0.000);Ⅱ组0.5 d时含量小于3 d时含量(t=-0.898,P=0.000),15 d时含量大于3 d和30 d时含量(t=7.106,P=0.000;t=7.750,P=0.000)。2组间血清骨形成蛋白-4含量总体有差别(F=69.398,P=0.000),Ⅰ组各时间点含量均高于Ⅱ组(t=5.027,P=0.000;t=3.124,P=0.006;t=5.080,P=0.000;t=6.100,P=0.000)。时间和分组因素存在交互作用(F=8.735,P=0.000)。结论:血清骨形成蛋白-4含量升高可能是脑外伤患者发生异位骨化的原因之一,适度控制脑外伤患者伤后血清骨形成蛋白-4含量可能会降低其异位骨化的发生率。

ABSTRACT Objective：To explore the relationship between serum bone morphogenetic protein-4 （BMP-4）levels and the appearance of heterotopic ossification, and to provide the corresponding theoretical basis for clinical prevention of beterotopic ossification. Methods：One hundred and forty-five traumatic patients selected from the patients treated in our hospital from December 2007 to January 2009 were divid- ed into 3 groups according to traumatic types. Fifty-seven patients with traumatic brain injury were included into group A, 48 cases with limbs fractures were included into group B, while the others with traumatic brain injury combined with limbs fractures were included into group C. After being hospitalized, patients were treated according to their traumatic types. Serum BMP-4 contents of patients were measured through blood sampling in cubital vein on 0.5 d ,3 d, 15 d and 30 d postinjury. The shoulder,elbow,hip and knee joints of patients were inspected by X-ray examination when following up 14-16 months later. Then the patients were divided into 2 groups according to the appearance of heterotopic ossification：patients with heterotopic ossification were included into group Ⅰ, while the others without heterotopic ossification were included into group Ⅱ. The heterotopic ossification occurrences for patients were compared among group A, group B and group C, and the serum BMP-4 contents at all the measuring time points were analyzed. Results ： （1）Occurrences of heterotopic ossification ： among the 145 patients, 17 cases were found with heterotopic ossification（ group I ）,while the others were found without heterotopic ossification （ group Ⅱ ）. There was statistical difference in occurrences of heterotopic ossification among group A, B＆C （X2 = 8. 131 ,P = 0.017 ）. For the further multiple comparisons（ Adjustment of inspection level：a＇ = 0. 017） ：the rate of heterotopic ossification in group A was higher than that in group B （X2 = 6. 430, P = 0.011 ） , while there was no statistical difference between any other groups （ group A vs group C ：X2 = 3. 303, P = 0. 069, group B vs group C ：X2 = 0. 044, P = 0. 834）. （2）Serum BMP-4 contents in group A, B＆C ： BMP-4 contents were different at different time points（ F = 41. 753 ,P = 0. 000）. For group A, there was no statistical difference in contents between 0. 5 d and 3 d（ t = -0. 479, P = 0. 633 ） ,while the content at 15 d was higher than that at 3 d and 30 d respectively（ t = 7. 134, P = 0. 000;t = 7. 338, P = 0. 000）. For group B, there was no statistical difference in serum BMP-4 contents among different time points （ F = 0. 510,P = 0. 678 ）. For group C, there was no statistical difference in contents compared between 0.5 d and 3 d（ t = - 0. 767,P = 0. 446） ,while the content at 15 d was higher than that at 3 d and 30 d respectively（ t = 5. 725,P = 0. 000 ; t = 4. 326,P = 0. 000）. There was difference in serum BMP-4 contents among the 3 groups totally（ F = 122. 299 ,P = 0.000）. For the further comparision ： content of group A was higher than that of group B＆C at 0.5 d （ t = 5.391 ,P = 0. 000 ; t = 5. 567, P = 0. 000 ） ; so did the contents at 3 d （ t = 4. 678, P = 0. 000 ; t = 3. 848, P = 0. 000 ）. The serum BMP-4 contents of group A was higher than that of group B＆C at 15 d （ t = 12. 007,P = 0. 000 ;t = 6. 561 ,P = 0. 000）, and content of group B was lower than that of group C（ t = - 7. 591 ,P = 0. 000）. The content of group A was higher than that of group B＆C at 30 d （ t = 7. 094, P = 0. 000 ; t = 3.581, P = 0. 000） , and content of group B was lower than that of group C （ t = - 3. 753, P = 0. 000 ）. There was interaction between time and grouping factors （ F = 18. 404, P = 0. 000）. （3）Serum BMP-4 contents in group Ⅰ ＆ Ⅱ ： serum BMP-4 contents were different at different time points（ F =40. 910,P =0. 000）. For group I ,there was no statistical difference in contents between 0.5 d and 3 d（ t = 0. 335 ,P = 0. 740）, while the content at 15 d was higher than that at 3 d and 30 d respectively （t = 4. 586, P = 0. 000;t = 3. 796, P = 0. 000 ）. For group Ⅱ , the content at 0.5 d was lower than that at 3 d （ t = - 0. 898, P = 0. 000） , and content at 15 d was higher than that at 3 d and 30 d respectively（t =7. 106,P =0. 000;t =7. 750,P =0. 000）. There was difference in serum BMP-4 contents between the 2 groups totally （ F = 69. 398, P = 0.000）, and the contents of group I at all the time points were all higher than those of group Ⅱ（ t = 5. 027, P = 0. 000 ; t = 3.124, P = 0. 006 ; t = 5. 080, P = 0. 000 ; t = 6. 100, P = 0. 000）. There was interaction between time and grouping factors（ F = 8. 735,P = 0. 000）. Conclusion：Increasing of serum BMP-4 contents may be one of the reasons of occurring heterotopic ossification for patients with traumatic brain injury, therefore,the incidence rate of heterotopic ossification may decrease by controlling of serum BMP-4 contents postinjury properly.