自然铜合方在股骨干骨折术后骨不连脾肾两虚夹瘀证治疗中的应用

Application of pyritum integrated decoction in treatment of spleen-kidney-deficiency-blood-stasis-type postoperative nonunion of femoral shaft fractures

目的:探讨自然铜合方在股骨干骨折术后骨不连脾肾两虚夹瘀证治疗中的应用价值。方法:回顾性分析2010年1月至2017年6月40例股骨干骨折交锁髓内钉内固定术后骨不连脾肾两虚夹瘀证患者的病例资料,自然铜合方组和碳酸钙D3组各20例。2组患者采用原内固定方式重新固定骨折并在骨折端植骨后,均予以碳酸钙D3片口服,每次2片,每日1次;自然铜合方组患者在此基础上予以自然铜合方水煎服,每日1剂,早晚各1次。治疗9个月后,检测2组患者骨密度,并参照《骨科学》中骨折临床愈合评价标准评价疗效。分别于治疗前和治疗3个月后、6个月后、9个月后,检测血清骨钙素(bone glaprotein,BGP)、骨保护素(osteoprotegerin,OPG)、Ⅰ型胶原N末端肽(collagen typeⅠN-telepeptide,NTX)、抗酒石酸酸性磷酸酶5b(tartrate resistant acid phosphatase-5b,TRACP-5b)水平观察骨代谢情况,检测血清谷草转氨酶(aspartate aminotransferase,AST)、谷丙转氨酶(alanine aminotransferase,ALT)、肌酐(creatinine,Cr)水平评价肝肾功能。结果:①骨密度和临床疗效。治疗前2组患者骨密度比较,差异无统计学意义[(0.91±0.06)g·cm^-2,(0.93±0.05)g·cm^-2,t=4.109,P=0.197];治疗9个月后,2组患者骨密度均比治疗前提高[(0.91±0.06)g·cm^-2,(1.38±0.04)g·cm^-2,t=25.900,P=0.000;(0.93±0.05)g·cm^-2,(1.07±0.03)g·cm^-2,t=8.994,P=0.000],且自然铜合方组骨密度高于碳酸钙D3组(t=26.684,P=0.000)。自然铜合方组骨折临床愈合13例、好转6例、无效1例,碳酸钙D3组骨折临床愈合6例、好转8例、无效6例,自然铜合方组临床疗效优于碳酸钙D3组(Z=-2.472,P=0.013)。②血清BGP水平。时间因素和分组因素存在交互效应(F=3.343,P=0.022);2组患者血清BGP水平总体比较,差异有统计学意义,即存在分组效应(F=8.398,P=0.006);治疗前后不同时间点之间患者血清BGP水平的差异有统计学意义,即存在时间效应(F=64.142,P=0.000);2组患者血清BGP水平随时间变化总体上均呈上升趋势,但2组的上升趋势不完全一致;治疗前和治疗3个月后,2组患者血清BGP水平比较,差异均无统计学意义[(4.47±0.18)μg·L^-1,(4.55±0.28)μg·L^-1,t=-1.063,P=0.295;(4.96±0.28)μg·L^-1,(4.80±0.31)μg·L^-1,t=1.605,P=0.117];治疗6个月后和治疗9个月后,自然铜合方组血清BGP水平均高于碳酸钙D3组[(5.19±0.24)μg·L^-1,(4.98±0.29)μg·L^-1,t=2.437,P=0.020;(5.42±0.24)μg·L^-1,(5.15±0.31)μg·L^-1,t=3.054,P=0.004]。③血清OPG水平。时间因素和分组因素存在交互效应(F=26.320,P=0.000);2组患者血清OPG水平总体比较,差异有统计学意义,即存在分组效应(F=118.438,P=0.000);治疗前后不同时间点之间患者血清OPG水平的差异有统计学意义,即存在时间效应(F=136.254,P=0.000);2组患者血清OPG水平随时间变化总体上均呈上升趋势,但2组的上升趋势不完全一致;治疗前和治疗3个月后,2组患者血清OPG水平比较,差异均无统计学意义[(5.98±0.26)μg·L^-1,(5.85±0.22)μg·L^-1,t=1.677,P=0.102;(6.47±0.27)μg·L^-1,(6.37±0.22)μg·L^-1,t=1.314,P=0.197];治疗6个月后和治疗9个月后,自然铜合方组血清OPG水平均高于碳酸钙D3组[(7.14±0.23)μg·L^-1,(6.41±0.24)μg·L^-1,t=10.053,P=0.000;(7.34±0.29)μg·L^-1,(6.50±0.25)μg·L^-1,t=9.861,P=0.000]。④血清NTX水平。时间因素和分组因素存在交互效应(F=3.549,P=0.017);2组患者血清NTX水平总体比较,差异有统计学意义,即存在分组效应(F=10.885,P=0.002);治疗前后不同时间点之间患者血清NTX水平的差异有统计学意义,即存在时间效应(F=163.624,P=0.000);2组患者血清NTX水平随时间变化总体上均呈降低趋势,但2组的降低趋势不完全一致;治疗前和治疗3个月后,2组患者血清NTX水平比较,差异均无统计学意义[(4.49±0.23)μg·L^-1,(4.35±0.35)μg·L^-1,t=1.422,P=0.163;(4.25±0.29)μg·L^-1,(4.29±0.31)μg·L^-1,t=-0.421,P=0.676];治疗6个月后和治疗9个月后,自然铜合方组血清NTX水平均高于碳酸钙D3组[(3.46±0.44)μg·L^-1,(3.10±0.29)μg·L^-1,t=3.051,P=0.004;(3.47±0.33)μg·L^-1,(3.18±0.24)μg·L^-1,t=3.250,P=0.002]。⑤血清TRACP-5b水平。时间因素和分组因素存在交互效应(F=9.164,P=0.000);2组患者血清TRACP-5b水平总体比较,差异有统计学意义,即存在分组效应(F=32.210,P=0.000);治疗前后不同时间点之间患者血清TRACP-5b水平的差异有统计学意义,即存在时间效应(F=353.626,P=0.000);2组患者血清TRACP-5b水平随时间变化总体上均呈降低趋势,但2组的降低趋势不完全一致;治疗前,2组患者血清TRACP-5b水平比较,差异无统计学意义[(8.40±0.35)μg·L^-1,(8.33±0.32)μg·L^-1,t=0.747,P=0.459];治疗3个月后、6个月后和9个月后,自然铜合方组血清TRACP-5b水平均低于碳酸钙D3组[(6.39±0.32)μg·L^-1,(6.69±0.46)μg·L^-1,t=-2.392,P=0.022;(6.13±0.32)μg·L^-1,(6.78±0.30)μg·L^-1,t=-6.605,P=0.000;(6.08±0.25)μg·L^-1,(6.56±0.36)μg·L^-1,t=-4.907,P=0.000]。(6)血清AST、ALT、Cr水平。时间因素和分组因素均不存在交互效应(F=2.629,P=0.054;F=0.203,P=0.894;F=0.272,P=0.845);治疗前,自然铜合方组血清AST水平低于碳酸钙D3组[(18.46±6.83)μmol·L^-1,(23.29±6.99)μmol·L^-1,t=-2.210,P=0.033],但2组患者血清AST、ALT、Cr水平总体比较,组间差异均无统计学意义,即均不存在分组效应(F=1.364,P=0.250;F=1.328,P=0.256;F=0.468,P=0.498);治疗前后不同时间点之间患者血清AST、ALT、Cr水平的差异均无统计学意义,即均不存在时间效应(F=0.786,P=0.504;F=0.582,P=0.628;F=0.986,P=0.402)。结论:对于股骨干骨折术后骨不连脾肾两虚夹瘀证患者,在二次固定并植骨的基础上,口服自然铜合方和碳酸钙D3片比单纯口服碳酸钙D3片,在调节骨代谢、增加骨密度、促进骨折愈合方面更有优势,且二者对患者肝肾功能的影响相当。

Objective:To explore the applied values of pyritum integrated decoction in treatment of spleen-kidney-deficiency-blood-sta sis-type postoperative nonunion of femoral shat fractures.Metliods:The medical records of 40 patients with spleen-kidney-deficiency-blood-stasis-type fracture nonunion ater internal fixation with interlocking intramedullary nail for treatment of femoral shat fractures from January 2010 to June 2017 were analyzed retrospectively.Twenty patients were treated with pyritum integrated decoction(pyritum integrated decoc tion group),while the others were treated with calcium carbonate D3(calcium carbonate D3 group).All patients in the 2 groups were trea ted with oral applications of calcium carbonate D3 tablets ater the fractures were refixed with initial internal fixation method and bone graft ing were conducted at the broken ends of fractured femoral shaft,once a day,2 tablets at a time.Moreover,the patients in pyritum integrated decoction group were treated with pyritum integrated decoction,one dose a day in the morning and evening respectively.After 9-month treatment,the bone mineral density(BMD)was measured in the 2 groups,and the curative effects were evaluated according to clinical frac ture healing evaluation standard which was extracted from ORTHOPAEDICS.The serum levels of bone glaprotein(BGP),osteoprotegerin(OPG),collagen type Ⅰ N-telepeptide(NTX)and tartrate resistant acid phosphatase-5b(TRACP-5b)were detected for evaluating bone metabolism and the serum levels of aspartate aminotransferase(AST),alanine aminotransferase(ALT)and creatinine(Cr)were detected for evaluating functions of liver and kidney before the treatment and after 3-,-and 9-month treatment respectively.Results:There was no statistical difference in the BMDbetween the 2 groups before the treatment(0.91+/-0.06 vs 0.93+/-0.05 gcm(2),=4.109,P=0.197).The BMD increased in the 2 groups ater 9-month treatment compared to pre-treatment(0.91+/-0.06 vs 1.38+/-0.04 gcm(2),=25.900,P=0.000;0.93+/-0.05 vs 1.07+/-0.03 gcm(2),=8.994,P=0.000),nd the BMD was higher in pyritum integrated de coction group compared to calcium carbonate D3 group(t=26.684,P=0.000).Thirteen patients healed,good and 1 poor in pyritum in tegrated decoction group;while 6 patients healed,good and 6 poor in calcium carbonate D3 group.The pyritum integrated decoction group surpassed calcium carbonate D3 group in clinical curative effects(Z=-2.472,P=0.013).There was interaction between time factor and group factor in serum level of BGP(F=3.343,P=0.022).There was statistical difference in serum level of BGP between the 2 groups in general,in other words,there was group effect(F=8.398,P=0.006).There was statistical difference in serum level of BGP between dif ferent timepoints before and ater the treatment,in other words,there was time effect(F=64.142,P=0.000).The serum level of BGP presented a time-dependent increasing trend in the 2 groups in general,while the 2 groups were inconsistent with each other in the varia-tiontendency.There was no statistical difference insernmlevel of BGP betweenthe 2 groups before the treatment and after 3-month treat-ment(4.47+/-0.18 v 4.55+/-0.28 μg/Ly=-1.063,P=0.295;4.96+/-0.28 v 4.80+/-0.31 μg/Ly=1.605,P=0.117).The serum levels of BGP were higher in pyritum integrated decoction group compared to calcium carbonate D3 group after 6-and 9-month treatment(5.19+/-0.24 vs 4.98+/-0.29 μg/L,t=2.437=0.020;5.42+/-0.24 vs 5.15+/-0.31μg/L,t=3.054,P=0.004).There was interaction between time factor and group factor in serum level of OPG(F=26.320,P=0.000).There was statistical difference in serum level of OPG between the 2 groups in general,in other words,there was group effect(F=118.438,P=0.000).There was statisti cal difference in serum level of OPG between different timepoints before and ater the treatment,in other words,there was time effect(F=136.254,P=0.000).The serum level of OPG presented a time-dependent increasing trend in the 2 groups in general,while the 2 groups were inconsistent with each other in the variation tendency.There was no statistical difference in serum level of OPG between the 2 groups before the treatment and after 3-month treatment(5.98+/-0.26 vs 5.85+/-0.22 μg/L,t=1.677,P=0.102;6.47+/-0.27 vs 6.37+/-0.22μg/L,t=1.314,P=0.197).The sernmlevels of OPG were higher in pyrituminte/rated decoction/roup compared to calci um carbonate D3 group ater 6-and 9-month treatment(7.14+/-0.23 vs 6.41+/-0.24=10.053,P=0.000;7.34+/-0.29 vs 6.50+/-0.25 μg/L,t=9.861,P=0.000).There was interaction between time factor and group factor in serum level of NTX(F=3.549,P=0.017).There was statistical difference in serum level of NTX between the 2 groups in/eneral,in other words,there was group effect(F=10.885,P=0.002).There was statistical difference in serum level of NTX between different timepoints before and ater the treatment,in other words,there was time effect(F=163.624,P=0.000).The serum level of NTX presented a time-dependent decreasing trend in the 2 groups in general,while the 2 groups were inconsistent with each other in the variation tendency.There was no statistical difference in serum level of NTX between the 2 groups before the treatment and after 3-month treatment(4.49+/-0.23 vs 4.35+/-0.35μg/L,t=1.422,P=0.163;4.25+/-0.29 vs 4.29+/-0.31μg/L,=t-0.421,P=0.676).The serum levels of NTX were higher in pyritum integrated decoction group compared to calcium carbonate D3 group after 6-and 9-month treatment(3.46+/-0.44 vs 3.10+/-0.29 μg/L,t=3.051,P=0.004;3.47+/-0.33 vs 3.18+/-0.24 μg/L,t=3.250,P=0.002).There was interaction between time factor and group factor in serum level of TRACP-5b(F=9.164,P=0.000).There was statistical difference in serum level of TRACP-5b between the 2 groups ingeneral,in other words,there was group effect(F=32.210,P=0.000).There was statistical difference in serum level of TRACP-5b between different timepoints before and after the treatment,in other words,there was time effect(F=353.626,P=0.000).The serum level of TRACP-5b presented a time-dependent decreasing trend in the 2 groups ingeneral,while the 2 groups were inconsistent with each other in the variation tendency.There was no statistical difference in serum level of TRACP-5b between the 2 groups before the treatment(8.40+/-0.35 vs 8.33+/-0.32μg/L,t=0.747,P=0.459).The serum levels of TRACP-5b were lower in pyritum integrated decoction group compared to calcium carbonate D3 group after 3-,6-and 9-month treatment(6.39+/-0.32 v 6.69+/-0.46 μg/L,t=-2.392,P=0.022;6.13+/-0.32 v 6.78+/-0.30μg/L,t=-6.605,P=0.000;6.08+/-0.25 vs 6.56+/-0.36 μg/L,t=-4.907,P=0.000).There was no interaction between time factor and group factor in serum levels of AST,ALT and Cr(F=2.629,P=0.054;F=0.203,P=0.894;F=0.272,P=0.845).The serum level of AST was lower in pyri tum inte/rated decoction group compared to calcium carbonate D3 group before the treatment(18.46+/-6.83 vs 23.29+/-6.99 μmol/L,t=-2.210,P=0.033),while there was no statistical difference in serum levels of AST,ALT and Cr between the 2 groups ingeneral,in other words,there was no group effect(F=1.364,P=0.250;F=1.328,P=0.256;F=0.468,P=0.498).There was no statistical differ ence in serum levels of AST,ALT and Cr between different timepoints before and ater the treatment,in other words,there was no time effect(F=0.786,P=0.504;F=0.582,P=0.628;F=0.986,P=0.402).Conclusion:For patients with spleen-kidney-deficiency-blood-sta sis-type postoperative nonunion of femoral shat fractures,oral applications of pyritum integrated decoction and calcium carbonate D3 tablets is better than oral application of calcium carbonate D3 tablets in regulating bone metabolism,increasing bone density and promoting fracture healing,and they have similar effects on liver and kidney function.