补肾接骨汤联合碳酸钙D3片口服治疗老年骨质疏松性股骨转子间骨折肾虚血瘀证
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摘要
目的:观察补肾接骨汤联合碳酸钙D3片口服治疗老年骨质疏松性股骨转子间骨折肾虚血瘀证的临床疗效,并探讨其作用机制。方法:将107例老年骨质疏松性股骨转子间骨折股骨近端防旋髓内钉(proximal femoral nail antirotation,PFNA)内固定术后肾虚血瘀证患者随机分为2组。55例采用补肾接骨汤联合碳酸钙D3片口服治疗(联合组),52例采用碳酸钙D3片口服治疗(碳酸钙D3片组)。补肾接骨汤水煎服,每日1剂,连续服用12周;碳酸钙D3片口服,每日1片,连续服用12周。记录并比较2组患者的骨折愈合时间、髋部疼痛视觉模拟量表(visual analogue scale,VAS)评分,并分别于治疗前、治疗结束后比较2组患者骨保护素(osteoprotegerin,OPG)、核因子-κB受体活化因子配体(receptor activator of nuclear factor-κB ligand,RANKL)、转化生长因子(transforming growth factor,TGF)-β1、骨碱性磷酸酶(bone alkaline phosphatase,BALP)及抗酒石酸酸性磷酸酶5b(tartrate resistant acid phosphatase 5b,TRACP5b)血清含量。结果:①骨折愈合时间。联合组患者骨折愈合时间短于碳酸钙D3片组[(7. 85±1. 28)周,(8. 73±1. 18)周,t=3. 692,P=0. 000)]。②髋部疼痛VAS评分。时间因素和分组因素存在交互效应(F=37. 953,P=0. 000); 2组患者髋部疼痛VAS评分总体比较,组间差异有统计学意义,即存在分组效应(F=4. 269,P=0. 000);治疗前后不同时间点髋部疼痛VAS评分的差异有统计学意义,即存在时间效应(F=13. 274,P=0. 000); 2组患者髋部疼痛VAS评分随时间均呈下降趋势,且2组的下降趋势不完全一致[联合组:(7. 31±1. 25)分,(4. 13±0. 83)分,(2. 15±0. 58)分,F=5. 271,P=0. 000;碳酸钙D3片组:(7. 46±1. 02)分,(5. 08±0. 96)分,(2. 76±0. 42)分,F=3. 985,P=0. 000];治疗开始后1周2组患者髋部疼痛VAS评分比较,差异无统计学意义(t=0. 678,P=0. 499);治疗开始后3周、5周联合组髋部疼痛VAS评分均低于碳酸钙D3片组(t=5. 485,P=0. 000; t=6. 201,P=0. 000)。③骨愈合相关指标。治疗前2组患者OPG、RANKL、TGF-β1血清含量比较,组间差异均无统计学意义(t=0. 253,P=0. 800; t=0. 352,P=0. 726; t=1. 345,P=0. 181);治疗结束后2组患者OPG、RANKL、TGF-β1血清含量均高于治疗前[OPG:(4. 12±0. 84) pmol·L~(-1),(8. 57±1. 33) pmol·L~(-1),t=20. 980,P=0. 000;(4. 08±0. 79) pmol·L~(-1),(7. 16±1. 25) pmol·L~(-1),t=15. 020,P=0. 000。RANKL:(14. 63±3. 37) nmol·L~(-1),(32. 59±10. 95) nmol·L~(-1),t=11. 626,P=0. 000;(14. 85±3. 10) nmol·L~(-1),(41. 93±12. 15) nmol·L~(-1),t=16. 016,P=0. 000。TGF-β1:(227. 53±41. 28)μg·L~(-1),(380. 58±35. 66)μg·L~(-1),t=20. 807,P=0. 000;(237. 93±38. 52)μg·L~(-1),(312. 74±37. 51)μg·L~(-1),t=10. 034,P=0. 000],联合组患者OPG、TGF-β1血清含量均高于碳酸钙D3片组(t=5. 643,P=0. 000; t=9. 591,P=0. 000),RANKL血清含量低于碳酸钙D3片组(t=4. 169,P=0. 000)。④骨代谢相关指标。治疗前2组患者BALP、TRACP5b血清含量比较,组间差异无统计学意义(t=1. 170,P=0. 245; t=1. 750,P=0. 083);治疗结束后2组患者BALP血清含量均高于治疗前[联合组:(57. 48±4. 19)单位·L~(-1),(78. 43±3. 52)单位·L~(-1),t=28. 392,P=0. 000;碳酸钙D3片组:(56. 43±5. 07)单位·L~(-1),(65. 39±4. 85)单位·L~(-1),t=9. 289,P=0. 000],TRACP5b血清含量均低于治疗前[联合组:(7. 02±0. 47)单位·L~(-1),(4. 28±0. 30)单位·L~(-1),t=35. 715,P=0. 000;碳酸钙D3片组:(6. 84±0. 59)单位·L~(-1),(5. 11±0. 43)单位·L~(-1),t=17. 088,P=0. 000],联合组患者BALP血清含量高于碳酸钙D3片组(t=15. 980,P=0. 000),TRACP5b血清含量低于碳酸钙D3片组(t=11. 632,P=0. 000)。结论:补肾接骨汤联合碳酸钙D3片口服可有效缩短老年骨质疏松性股骨转子间骨折肾虚血瘀证患者的骨折愈合时间,减轻患者术后疼痛,其作用机制可能与其改善骨代谢、促进成骨细胞活化以及抑制破骨细胞过度活化有关。
Objective: To observe the clinical curative effects of oral application of Bushen Jiegu Tang (补肾接骨汤,BSJGT) and calcium carbonate and Vitamin D3 tablets for treatment of kidney-deficiency-blood-stasis-type osteoporotic femoral intertrochanteric fractures in aged patients and to explore its mechanism of action. Methods: One hundred and seven aged patients who suffered from kidney-deficiency-blood-stasis syndrome after proximal femoral nail antirotation (PFNA) internal fixation for treatment of osteoporotic femoral intertrochanteric fracture were randomly divided into 2 groups. Fifty-five patients were treated with oral application of BSJGT and calcium carbonate and Vitamin D3 tablets (combination therapy group),while the others were treated with oral application of calcium carbonate and Vitamin D3 tablets (monotherapy group). The BSJGT decoctions were taken one dose a day for consecutive 12 weeks. The calcium carbonate and Vitamin D3 tablets were taken one tablet a day for consecutive 12 weeks. The fracture healing time and hip pain visual analogue scale (VAS) scores were recorded and compared between the 2 groups. The serum contents of osteoprotegerin (OPG),receptor activator of nuclear factor-κB ligand (RANKL),transforming growth factor-β1 (TGF-β1),bone alkaline phosphatase (BALP) and tartrate resistant acid phosphatase 5 b (TRACP5 b) were detected and compared between the 2 groups before the treatment and after the end of the treatment respectively. Results: The fracture healing time was shorter in combination therapy group compared to monotherapy group (7. 85 +/-1. 28 vs8. 73 +/-1. 18 weeks,t = 3. 692,P = 0. 000). There was interaction between time factor and group factor in hip pain VAS scores (F =37. 953,P = 0. 000). There was statistical difference in hip pain VAS scores between the 2 groups in general,in other words,there was group effect (F = 4. 269,P = 0. 000). There was statistical difference in hip pain VAS scores between different timepoints before and after the treatment,in other words,there was time effect (F = 13. 274,P = 0. 000). The hip pain VAS scores presented a time-dependent decreasing trend in both of the 2 groups,while the 2 groups were inconsistent with each other in the decreasing trend of hip pain VAS scores (combination therapy group: 7. 31 +/-1. 25,4. 13 +/-0. 83,2. 15 +/-0. 58 points,F = 5. 271,P = 0. 000; monotherapy group: 7. 46 +/-1. 02,5. 08 +/-0. 96,2. 76 +/-0. 42 points,F = 3. 985,P = 0. 000). There was no statistical difference in hip pain VAS scores between the2 groups at 1 week after the beginning of the treatment (t = 0. 678,P = 0. 499). The hip pain VAS scores were lower in combination therapy group compared to monotherapy group at 3 and 5 weeks after the beginning of the treatment (t = 5. 485,P = 0. 000; t = 6. 201,P = 0. 000).There was no statistical difference in serum contents of OPG,RANKL and TGF-β1 between the 2 groups before the treatment (t = 0. 253,P = 0. 800; t = 0. 352,P = 0. 726; t = 1. 345,P = 0. 181). The serum contents of OPG,RANKL and TGF-β1 were higher after the end of the treatment compared to pre-treatment in the 2 groups (OPG: 4. 12 +/-0. 84 vs 8. 57 +/-1. 33 pmol/L,t = 20. 980,P = 0. 000;4. 08 +/-0. 79 vs 7. 16 +/-1. 25 pmol/L,t = 15. 020,P = 0. 000. RANKL: 14. 63 +/-3. 37 vs 32. 59 +/-10. 95 nmol/L,t = 11. 626,P =0. 000; 14. 85 +/-3. 10 vs 41. 93 +/-12. 15 nmol/L,t = 16. 016,P = 0. 000. TGF-β1: 227. 53 +/-41. 28 vs 380. 58 +/-35. 66 μg/L,t = 20. 807,P = 0. 000; 237. 93 +/-38. 52 vs 312. 74 +/-37. 51 μg/L,t = 10. 034,P = 0. 000). The serum contents of OPG and TGF-β1 were higher and the serum content of RANKL was lower in combination therapy group compared to monotherapy group (t = 5. 643,P =0. 000; t = 9. 591,P = 0. 000; t = 4. 169,P = 0. 000). There was no statistical difference in serum contents of BALP and TRACP5 b between the 2 groups before the treatment (t = 1. 170,P = 0. 245; t = 1. 750,P = 0. 083). The serum content of BALP was higher and the serum content of TRACP5 b was lower after the end of the treatment compared to pre-treatment in the 2 groups (combination therapy group:57. 48 +/-4. 19 vs 78. 43 +/-3. 52 unit/L,t = 28. 392,P = 0. 000; 7. 02 +/-0. 47 vs 4. 28 +/-0. 30 unit/L,t = 35. 715,P = 0. 000; monotherapy group: 56. 43 +/-5. 07 vs 65. 39 +/-4. 85 unit/L,t = 9. 289,P = 0. 000; 6. 84 +/-0. 59 vs 5. 11 +/-0. 43 unit/L,t = 17. 088,P =0. 000). The serum content of BALP was higher and the serum content of TRACP5 b was lower in combination therapy group compared to monotherapy group (t = 15. 980,P = 0. 000; t = 11. 632,P = 0. 000). Conclusion: Oral application of BSJGT and calcium carbonate and Vitamin D3 tablet can effectively shorten fracture healing time and relieve postoperative pain in aged patients with kidney-deficiency-blood-stasis-type osteoporotic femoral intertrochanteric fractures,and its mechanisms of action may be that it can improve bone metabolism,promote osteoblast activation and inhibit osteoclast overactivation.
Objective: To observe the clinical curative effects of oral application of Bushen Jiegu Tang (补肾接骨汤,BSJGT) and calcium carbonate and Vitamin D3 tablets for treatment of kidney-deficiency-blood-stasis-type osteoporotic femoral intertrochanteric fractures in aged patients and to explore its mechanism of action. Methods: One hundred and seven aged patients who suffered from kidney-deficiency-blood-stasis syndrome after proximal femoral nail antirotation (PFNA) internal fixation for treatment of osteoporotic femoral intertrochanteric fracture were randomly divided into 2 groups. Fifty-five patients were treated with oral application of BSJGT and calcium carbonate and Vitamin D3 tablets (combination therapy group),while the others were treated with oral application of calcium carbonate and Vitamin D3 tablets (monotherapy group). The BSJGT decoctions were taken one dose a day for consecutive 12 weeks. The calcium carbonate and Vitamin D3 tablets were taken one tablet a day for consecutive 12 weeks. The fracture healing time and hip pain visual analogue scale (VAS) scores were recorded and compared between the 2 groups. The serum contents of osteoprotegerin (OPG),receptor activator of nuclear factor-κB ligand (RANKL),transforming growth factor-β1 (TGF-β1),bone alkaline phosphatase (BALP) and tartrate resistant acid phosphatase 5 b (TRACP5 b) were detected and compared between the 2 groups before the treatment and after the end of the treatment respectively. Results: The fracture healing time was shorter in combination therapy group compared to monotherapy group (7. 85 +/-1. 28 vs8. 73 +/-1. 18 weeks,t = 3. 692,P = 0. 000). There was interaction between time factor and group factor in hip pain VAS scores (F =37. 953,P = 0. 000). There was statistical difference in hip pain VAS scores between the 2 groups in general,in other words,there was group effect (F = 4. 269,P = 0. 000). There was statistical difference in hip pain VAS scores between different timepoints before and after the treatment,in other words,there was time effect (F = 13. 274,P = 0. 000). The hip pain VAS scores presented a time-dependent decreasing trend in both of the 2 groups,while the 2 groups were inconsistent with each other in the decreasing trend of hip pain VAS scores (combination therapy group: 7. 31 +/-1. 25,4. 13 +/-0. 83,2. 15 +/-0. 58 points,F = 5. 271,P = 0. 000; monotherapy group: 7. 46 +/-1. 02,5. 08 +/-0. 96,2. 76 +/-0. 42 points,F = 3. 985,P = 0. 000). There was no statistical difference in hip pain VAS scores between the2 groups at 1 week after the beginning of the treatment (t = 0. 678,P = 0. 499). The hip pain VAS scores were lower in combination therapy group compared to monotherapy group at 3 and 5 weeks after the beginning of the treatment (t = 5. 485,P = 0. 000; t = 6. 201,P = 0. 000).There was no statistical difference in serum contents of OPG,RANKL and TGF-β1 between the 2 groups before the treatment (t = 0. 253,P = 0. 800; t = 0. 352,P = 0. 726; t = 1. 345,P = 0. 181). The serum contents of OPG,RANKL and TGF-β1 were higher after the end of the treatment compared to pre-treatment in the 2 groups (OPG: 4. 12 +/-0. 84 vs 8. 57 +/-1. 33 pmol/L,t = 20. 980,P = 0. 000;4. 08 +/-0. 79 vs 7. 16 +/-1. 25 pmol/L,t = 15. 020,P = 0. 000. RANKL: 14. 63 +/-3. 37 vs 32. 59 +/-10. 95 nmol/L,t = 11. 626,P =0. 000; 14. 85 +/-3. 10 vs 41. 93 +/-12. 15 nmol/L,t = 16. 016,P = 0. 000. TGF-β1: 227. 53 +/-41. 28 vs 380. 58 +/-35. 66 μg/L,t = 20. 807,P = 0. 000; 237. 93 +/-38. 52 vs 312. 74 +/-37. 51 μg/L,t = 10. 034,P = 0. 000). The serum contents of OPG and TGF-β1 were higher and the serum content of RANKL was lower in combination therapy group compared to monotherapy group (t = 5. 643,P =0. 000; t = 9. 591,P = 0. 000; t = 4. 169,P = 0. 000). There was no statistical difference in serum contents of BALP and TRACP5 b between the 2 groups before the treatment (t = 1. 170,P = 0. 245; t = 1. 750,P = 0. 083). The serum content of BALP was higher and the serum content of TRACP5 b was lower after the end of the treatment compared to pre-treatment in the 2 groups (combination therapy group:57. 48 +/-4. 19 vs 78. 43 +/-3. 52 unit/L,t = 28. 392,P = 0. 000; 7. 02 +/-0. 47 vs 4. 28 +/-0. 30 unit/L,t = 35. 715,P = 0. 000; monotherapy group: 56. 43 +/-5. 07 vs 65. 39 +/-4. 85 unit/L,t = 9. 289,P = 0. 000; 6. 84 +/-0. 59 vs 5. 11 +/-0. 43 unit/L,t = 17. 088,P =0. 000). The serum content of BALP was higher and the serum content of TRACP5 b was lower in combination therapy group compared to monotherapy group (t = 15. 980,P = 0. 000; t = 11. 632,P = 0. 000). Conclusion: Oral application of BSJGT and calcium carbonate and Vitamin D3 tablet can effectively shorten fracture healing time and relieve postoperative pain in aged patients with kidney-deficiency-blood-stasis-type osteoporotic femoral intertrochanteric fractures,and its mechanisms of action may be that it can improve bone metabolism,promote osteoblast activation and inhibit osteoclast overactivation.
引文
[1]柯新,孙亭方.两种内固定治疗老年骨质疏松性股骨粗隆骨折后对TGF-β2表达的影响及疗效比较[J].生物骨科材料与临床研究,2017,14(2):52-54.
[2]邹泽良.甲状旁腺激素联合葛根素对老年骨质疏松性股骨粗隆骨折术后影响的临床观察[J].中国骨质疏松杂志,2017,23(8):1081-1085.
[3]张牧龙.通脉汤对老年股骨粗隆间骨折内固定治疗髋关节功能及骨密度影响[J].实用中医药杂志,2017,33(5):466-467.
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[6]张智海,刘忠厚,李娜,等.中国人骨质疏松症诊断标准专家共识[J].中国骨质疏松杂志,2014,20(9):1007-1010.
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[2]邹泽良.甲状旁腺激素联合葛根素对老年骨质疏松性股骨粗隆骨折术后影响的临床观察[J].中国骨质疏松杂志,2017,23(8):1081-1085.
[3]张牧龙.通脉汤对老年股骨粗隆间骨折内固定治疗髋关节功能及骨密度影响[J].实用中医药杂志,2017,33(5):466-467.
[4]胥少汀,葛宝丰,徐印坎.实用骨科学[M].3版.北京:人民军医出版社,2005:1737-1745.
[5]中华中医药学会.中医骨伤科常见病诊疗指南[M].北京:中国中医药出版社,2012:154-157.
[6]张智海,刘忠厚,李娜,等.中国人骨质疏松症诊断标准专家共识[J].中国骨质疏松杂志,2014,20(9):1007-1010.
[7]郑筱萸.中药新药临床研究指导原则(试行)[M].北京:中国医药科技出版社,2002:85-86.
[8]王志,汤健,华兴一.Inter Tan髓内钉与股骨近端防旋髓内钉治疗老年性股骨粗隆间骨折的Meta分析[J].安徽医学,2018,39(2):136-140.
[9]张建洛,张飞.股骨近端防旋髓内钉联合中药治疗高龄股骨粗隆骨折临床研究[J].河南中医,2016,36(8):1399-1401.
[10]何星宏.中医正骨手法复位外固定与西医手术内固定治疗老年股骨粗隆间骨折的疗效比较[J].现代中西医结合杂志,2014,23(22):2431-2433.
[11]邓智刚.PFNA、DHS在治疗高龄患者股骨粗隆骨折中的应用[J].临床医学工程,2013,20(1):55-56.
[12]钟敏,杨斌,曾明,等.探究关节置换法治疗老年骨质疏松性股骨粗隆骨折患者临床疗效[J].中国伤残医学,2017,25(13):34-36.
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