摘要
目的:探讨中医学对绝经后骨质疏松症的认识,采用滋补肝肾壮骨方治疗绝经后骨质疏松症,客观评价滋补肝肾壮骨方对绝经后骨质疏松症肝肾阴虚证患者的治疗效果,尤其是对临床症状、骨密度测定(BMD)、血清钙、磷、雌二醇(E2)、血清睾酮(T),白介素-6(IL-6)等方面所产生的影响,并评价其安全性,为临床应用提供客观依据。
方法:采用随机、对照的研究方法,将符合绝经后骨质疏松症的患者,随机分为对照组和治疗组。在基础治疗和西药常规治疗的基础上,对照组给予口服阿法D3胶丸(阿法骨化醇),0.25ug,每日2次;钙尔奇D,600mg,每日1次;治疗组给予滋补肝肾壮骨方中药水煎剂,每日1剂,分早晚两次服用。以4周为1个疗程,观察3个疗程。治疗前后两组分别评价其临床症状、体征的变化,治疗前后观测骨密度、血清钙、磷、雌二醇、睾酮、白介素-6等指标。全部数据以SPSS16.0统计软件进行统计学分析。
结果:绝经后骨质疏松症患者50例随机分为2组,治疗组25例,对照组25例,治疗前两组的年龄、病程、中医症状等基线数据经统计学处理无显着性差异,有可比性。其结果如下:①对症状体征的改善作用:治疗组患者治疗后症状有明显改善,治疗组中医症状改善情况明显优于对照组(P<0.05)。②提高骨密度:治疗后治疗组患者BMD均明显升高,有显著性差异(P<0.01);对照组较治疗前无明显差异(P>0.05)。治疗组BMD的变化与对照组相比,差异有统计学意义(P<0.05)。③对血钙、磷的影响:治疗后两组患者血钙均升高,但差异无统计学意义(P>0.05);治疗后两组患者血磷均有所降低,但差异无统计学意义(P>0.05);治疗组血钙、血磷的变化较对照组无显著性差异(P>0.05)。④调节性激素水平:患者性激素比较,治疗组E2较治疗前明显升高(P<0.01);T较治疗前明显降低(P<0.01)。组间比较,E2的升高幅度明显大于对照组(P<0.01),T的降低幅度大于对照组,差异有统计学意义(P<0.05)。⑤对IL-6影响:治疗组IL-6较治疗前也有显著性改善(P<0.01),与对照组比较均有差异(P<0.01)。⑥安全性指标:治疗组患者血、尿、粪常规及肝肾功能检查均在正常范围。两组均未见不良反应。
结论:从初步临床研究来看,滋补肝肾壮骨方治疗绝经后骨质疏松症肝肾阴虚证,可明显改善患者的临床症状;在西医学指标方面,可以改善骨密度,调节性激素水平,且无肝肾功能损害,治疗本病安全、有效,有广泛的应用前景。但由于本人为境外学生,能力和条件限制,本研究病例数相对较少,今后需进一步深入研究。
Purpose:To discuss the understanding of traditional Chinese medicine about postmenopausal osteoporosis, using the therapy of renal-vital-reinforce and Bone-vital-strong Prescription to treat postmenopausal osteoporosis.To observe the therapeutic efficacy of this prescription in treating postmenopausal osteoporosis with deficiency of liver-yin and kidney-yin symptoms by the indexes such as clinical symptom, bone mineral density(BMD), serum calcium and phosphorus, estradiol, testoterone, interleukin-6(IL-6).Then evaluating its safety, so as to guide its clinical application.
Methods:A randomized, controlled trial was conducted.The patients of postmenopausal osteoporosis were randomly classified into two groups.On the basic of normal treatment and western medicine, the patients of treated group were treated by Chinese medicine while the patients of controlled group were treated by Alfacalcidol Capsule and Caltrate Vitamin D3Tabletas.,which was observed for3month and four weeks were a course of treatment..The observed indexes included curative effect indexes, such as clinic symptoms, bone mineral density, serum calcium and phosphorus, estradiol, testoterone, interleukin-6and so on. The complete data carries on statistics analysis by the SPSS16.0statistics software.
Results:The diagnosis and included postmenopausal osteoporosis patients with50cases.25cases of treated group,while25cases of controlled group.Prior treatment,age,course of disease of the two groups patients had no differeces.1.Symptoms and signs improvement:the treated group after treatment had a significant improvement. The symptoms improvement of the treated group was better than the controlled group (P<0.05).2. Bone mineral density:After treatment, the BMD of the treated group were significantly higher than controlled group(P<0.01) while the controlled group had no statistical significance(P>0.05).The BMD of the treated group had a difference than controlled group(P<0.05).3. Serum calcium and phosphate:Serum calcium of the two groups were higher, but had no statistical significance(P>0.05).Serum phosphate of the two groups were lower, but had no statistical significance.Serum calcium and phosphate of the controlled group had no statistical significance(P>0.05).4.Hormone:after treatment, the E2of the treated group was visibly higher(P<0.01) while the T was visibly lower(P<0.01).The improvement of E2of the treated group was better than the controlled group(P<0.01) and the improvement of T of the treated group was better than the controlled group, and had a statistical significance(P<0.05).5.IL-6:After treatment, the IL-6of the treated group were also significantly improved(P<0.01), and had a significantly difference than controlled group(P<0.01).6.Safety index:The routine blood/urine/feces test, and the liver and kidney function tests of treated group were within the normal range. Two groups had no unhealthy response.
Conclusion:Through the preliminary clinical study,chinese medicine of method has sure curative effected in treating postmenopausal osteoporosis with deficiency of liver-yin and kidney-yin.From the angle of western medicine,it is safe and can improve BMD,adjust hormone,and has no side-effect of liver and kidney. It is worth studying deeply and developing further.
引文
[1]金珉廷,郑洪新.中医肾藏精生髓主骨理论与骨质疏松症[J].辽宁中医药大学学报,2009,11(3):35-36
[2]郭世拔.骨质疏松基础与临床[M].天津:天津科学出版社,2001.
[3]李恩,薛延,王洪复,等.骨质疏松鉴别诊断与治疗[M].北京:人民卫生出版社,2005.
[4]中华医学会骨质疏松和骨矿盐疾病分会.原发性骨质疏松症诊治指南(2011年),中华骨质疏松和骨矿盐疾病杂志,2011,4(11):2-17.
[5]廖—元.更新知识、规范诊疗一应对骨质疏松症的高患病率[J].药品评价,2012,9(7):7.
[6]刘忠厚.骨矿与临床[M].中国科学技术出版社,2006,47.
[7]Semeets-Goevaers CG, Lesusink GL, et al.The prevalence of low bone mineral density in Duteh Perimenopausal women:the Eindhoven perimenopausal osteoporosis study[J]. Osteopros Int,1998,8(5): 404-409.
[8]粱裕,钱不凡,冯建民,等.骨折与骨质疏松症流行病学调查.上海第二医科大学学报,1997,17(4):308-310.
[9]马俊岭,郭海英,阳晓东.骨质疏松症的流行病学概况[J].中国全科医学,2009,12(18):1744-1746.
[10]胡军,张华,牟青.骨质疏松症的流行病学趋势与防治进展[J].临床荟萃.2011,26(8):730.
[11]徐苓.骨质疏松症[M].上海:上海科学技术出版社,2011,11:63.
[12]刘庆思.中西医结合诊治骨质疏松症[M].中国中医药出版社,2001:10(1):5.
[13]王久和,常虹.植物雌激素防治绝经后骨质疏松症的研究进展[J].内蒙古医学院学报,2010,32(4):92.
[14]李万根,张彤.绝经后妇女骨密度与胰岛素、胰岛素样生长因子Ⅰ及瘦素的关系[J].中国临床康复,2004,8(24):36-37.
[15]章秋.原发性骨质疏松症的病因和发病机制[J].安徽医学,2003,23(2):2.
[16]王新祥,张允岭,黄启福.对骨质疏松症中医主要病机和现代病因学的认识与探讨[J].中西医结合学报,2010,8(12):1119.
[17]Mare J,Prezelj J,Komel R,et al.VDR genotype and response to etidronate therapy in late postmenopausal women[J]. Osteoporos Int,1999,10(4):303-306.
[18]刘文辉,辛先贵,荆雪宁等,原发性骨质疏松症的病机及防治理论探讨[J].辽宁中医杂志,2009,36(7):1107-1109.
[19]吴科锐.骨质疏松症的病因学研究进展[J].中外医疗,2011,30(17):191.
[20]莫风媚.女性原发性骨质疏松症的病因和检查方法[J].广西医学,2005,27(8):1199.
[21]Baile D.A, H.A. MeKay, R.L.Mirwald, P.R.E.Croeker, and R.A.Faulkner.A six-year longitudinal study of therelationship of physical activity to bone mineral accrual in growing children:the University of Saskatehewan Bone Mineral Accrual Study [J]. J.Bone Miner. Res.1999,14:1672-1679.
[22]中华医学会.临床诊疗指南:骨质疏松症和骨矿盐疾病分册[M].北京:人民卫生出版社,2006.12:3.
[23]张摇楠,章摇秋,骨代谢.骨生化指标在骨质疏松症中的应用[J],安徽医药,2011,15(4):401.
[24]Prevention and Management of Ost eoporosis. WHO technical report series, No921,2003,53-63.
[25]辛晓燕,蔡国青,绝经后骨质疏松症的诊断学进展[J],实用妇产科杂志2006年7月第22卷第7期,395-397.
[26]林华,韩祖斌,孙燕芳.DEXA和QUS在退行性骨关节病诊治中的应用[J].南京大学学报,2002,38:644-647.
[27]Wells G, Tugwel 1 P, Shea B, et al. MetaD analysis of the eff icacy of hormone replacement therapy in t reat ing and preventing ost eoporosis in postmenopausal women. The osteoporosis methodology group and the osteoporosis research advisory group[J]. Endocrine Rev,2001,23 (4):529-539.
[28]徐苓.适量补充钙和维生素D是防治骨质疏松症的基础措施——评新英格兰医学杂志Jackson等“补充钙和维生素D与骨折危险”一文.国际内分泌代谢杂志,2006,26(4):217-220.
[29]方岩,范辉,干燕慧.钙剂,维生素D与骨质疏松症[J].中国骨质疏松杂2011,17(8):723.
[30]胡琼,陆启滨.骨质疏松症治疗研究进展[J].长春中医药大学学报,2012,28(4):735-737.
[31]孙阳,杨茵.绝经后骨质疏松症药物防治的循证评价[J].实用妇产科杂志,2006,22(7):440-442.
[32]陈杰,贾晓燕,舒云均.骨质疏松症的防治研究进展[J].西南国防医药,2008,18(3):457-459.
[33]李青.雌孕激素治疗女性骨质疏松临床观察[J].中国误诊学杂志,2011,11(21):5088.
[34]包丽华,林华,李永军,等.伊班膦酸钠和阿仑膦酸钠对绝经后骨质疏松的干预研究[J].中国骨质疏松杂志,2011,17(3):232.
[35]连建强.降钙素治疗骨质疏松疝的研究进展[J].医学综述,2011,17(12):1860.
[36]许惠英.治疗骨质疏松症药物的应用进展[J].广东药学,2004,14(5):35-39.
[37]Dempst er DW, Cosman F, Kurland ES, et al. Effects of daily treatment with parathyroid hormone on bone microarchitecture and turnover in patient s with osteoporosis:a paired biopsy study[J]. J Bone Miner Res,2001,16:1846-1853.
[38]林华,徐天舒,范璐,等.5mg唑来膦酸治疗绝经后骨质疏松及其骨折[J].中华创伤骨科杂志,2012,14(1):31-35.
[39]孟萍.原发性骨质疏松症的非雌激素治疗[J].实用妇产科杂志,2006,22(7):389-391.
[40]王力群.老年性骨质疏松症的中医辨证论治[J].吉林中医药,2002,22(1):25.
[41]冯世纶.骨质疏松症的中医病名当议[J].中国骨质疏松杂志,2001,7(1):91.
[42]徐桂琴,谢雁鸣,张志斌.原发性骨质疏松症中医病名探讨[J],中国中医基础医学杂志,2009,15(9):651.
[43]朱辉,郑洪新.读《千金药方》谈骨质疏松症中医病名[J].吉林中医药,2009,29(10):910-911.
[44]肖荣华,李仁康,刘建国,等.女性肾虚证与女性健康人骨矿含量的分析[J].中国中西医结合杂志,1996,16(3):190.
[45]尚德阳.瘀血与骨质疏松症关系研究[J].辽宁中医药大学学报,2008,10(9):40-41
[46]眭承志,刘志坤,陈少玫,等.绝经后骨质疏松症与血瘀[J].中国中西医结合杂志,2005,25(5):457.
[47]金珉廷,郑洪新.骨质疏松症的中医体质学特征[J].中华中医药学刊,2009,27(4):824-826.
[48]孙益,童培建,肖鲁伟.绝经后骨质疏松症与中医体质的相关性[J].中医杂志,2009,50(8):696-698.
[49]张萌萌,李正树,杨传东,等99Tc-MDP治疗绝经后骨质疏松66例随访分析[J].中国妇幼保健,2006,21(3):372-373.
[50]谢雁鸣,朱芸茵,葛继荣,等.基于临床流行病学调查的原发性骨质疏松症中医基本证候研究[J].世界科学技术-中医药现代化,2007,9(2):38-44[51]张华,苏培基教授论治骨质疏松症经验总结[J].中医正骨,2008,20(2):63.
[52]徐祖健等.绝经后妇女原发性骨质疏松症中医辨证分型与骨密度的相关性研究[J].泸州医学院学报,2008,31(4):390.
[53]方朝晖,耿家金,张有志等.1000例老年性骨质疏松症证候分布与组合规律研究[J].中国中医药信息杂志,2007,14(5):15-16.
[54]袁瑛,袁兵.原发性骨质疏松症的中医治疗[J].中国骨质疏松杂志,2006,12(4):204-205.
[55]李中万,庄洪,李钊等ET—NO与绝经后骨质疏松症中医证型关系的临床初探[J].中国中医骨伤科杂志,2005,13(1):5-8.
[56]王长海,田立民等.中药骨松康治疗老年性骨质疏松症的临床对照研究[J].第四军医大学学报,2003,24(11):1029-1030.
[57]江湧,杨海韵.骨质疏松症从痿痹瘀痉辨治[J].新中医,2007,39(7):3.
[58]罗国良,吴陵.绝经后骨折与骨质疏松102例中医治疗[J].中国骨伤.1996,9(2):33.
[59]娄志杰,韩向莉,孙勤,等.骨质疏松症中医证型实质的研究思路[J].时珍国医国药,2007,18(12):3093-3094.
[60]翟远坤,葛宝丰,马慧萍,等.淫羊藿苷促进体外培养大鼠骨髓间充质干细胞的成骨性分化[J].中国中药杂志,2010,35(23):3219-3222.
[61]丁怀利,吴银生,林煜,等.大鼠成骨细胞RANKL-OPGmRNA表达的增龄性变化及淫羊藿甙的干预作用[J].中医正骨,2010,22(4):7-10.
[62]刘桦,白焱晶,陈亚云,等.中药补骨脂化学成分的研究[J].中国中药杂志,2008,33(12):1410-1412.
[63]宋芹,董小萍,郁小兵.补骨脂提取物对体外培养小鼠成骨细胞株MC3T3-E1细胞分化的影响[J].中国中药杂志,2009,34(10):1264-1267.
[64]舒晓春,胡向阳,张丽娟.骨碎补总黄酮对经诱导的兔骨髓间充质干细胞增殖和钙沉积的影响[J].中国中药杂志,2010,35(20):2760-2763.
[65]陈海啸,梁军波,伍海昭.骨碎补总黄酮对去卵巢大鼠腰椎松质骨形态计量学参数的影响[J].中医正骨,2011,23(4):18-20.
[66]周胜虎,刘兴炎,王湘辉,等.葛根素对卵巢切除大鼠血清E2、腰椎BMD及骨髓细胞IL-6mRNA表达的影响[J].中国骨质疏松杂志,2010,16(12):946-948.
[67]李俊发,潘子毅.葛根素对绝经后骨质疏松症患者血清IL-4、IL-6、IL-10和雌激素水平的影响[J].中国中医骨伤科杂志,2007,15(5):28-29.
[68]王和鸣,葛继荣,田金洲等.强骨胶囊治疗原发性骨质疏松症临床试验[J].中药新药与临床药理,2004,15(4):284.
[69]刘静仪,林如平.虎潜丸加减治疗骨质疏松症30例疗效观察[J].成都医药,2004,30(3):134.
[70]陈国权.中医药治疗骨质疏松症的探讨[J].中国临床医药研究杂志,2004,11(9):56.
[71]康国发.中药治疗痛性骨质疏松症[J].辽宁中医杂志,2004,31(7):581.
[72]张志峰.壮骨片治疗肾虚型原发性骨质疏松症45例疗效分析[J].中国临床康复,2004,18(7)3477.
[73]于波,崔宪春,谢进,等.复元活血汤含药血清对大鼠成骨细胞功能的影响[J].中医正骨,2011,23(1):17-21.
[74]潘小燕,王鸿度.针灸治疗原发性骨质疏松症的取穴规律[J].四川中医,2011,29(3):55.
[75]张红石,高颖,杨晓慧,等.补虚化瘀针法对骨质疏松大鼠形态计量学影响的研究[J].中国中医骨伤科杂志,2009,17(1):26-27.
[76]俞索静,李春雯,潘礼庆,等.脉冲电磁场对大鼠成骨细胞增殖影响的活细胞成像观察研究[J].中国骨质疏松杂志,2010,16(6):391-396.
[77]白孟海,葛宝丰,韦哲,等.脉冲电磁场对去势大鼠骨髓源细胞体外培养破骨细胞变化的影响[J].中国骨伤,2009,22(10):727-729.
[78]李瀚.“肝肾同源”的理论探讨[J].中国中医基础医学杂志,2000,6(7):5.
[79]刘忠厚.中国人骨质疏松症的建议诊断标准(第二稿)[J].中国骨质疏松杂志,2000,6(1):2.
[80]何才勇,叶有萍.原发性骨质疏松症的中医辨治[J].长春中医学院学报,2001,17(12):26-28.
[81]袁瑛,袁兵.原发性骨质疏松症的中医治疗仁[J].中国骨质疏松杂志,2006,12(4):204-205.
[82]黄宏兴,柴生颋,黄红等.骨质疏松症中医证型的聚类分析[J].广州中医药大学学报,2007,24(3):180.
[83]谢杰.应用模糊数学方法对绝经后骨质疏松症的证型研究[J].广州中医药大学,2007.
[84]杨大男,陈会琴,吴文设,等.肝肾亏虚证与骨矿物含量的相关性研究[J].临床荟萃,1996,11(4):176.
[85]杨洪彬,徐祖健,汪新象,等.绝经后女性骨质疏松症中医证型及证候分布规律的研究[J].四川中医杂志,2009,27(4):23-25.
[86]王和群.中医辨证治疗骨质疏松症疗效观察[J].内蒙古中医药,2007,26(3):223.
[87]费震宇,王文健.骨质疏松症的中医药治疗[J].现代康复,2001,5(4):26227.
[88]水正,水森.益肾祛疲法治疗老年骨质疏松症[J].上海预防医学杂志,1995,7(5):2302231.
[89]张荣华.益骨胶囊对去卵巢骨质疏松大鼠骨组织型胶原mRNA表达的影响[J].时珍国医国药,2005,16(10):941.
[90]杨帆,邓兆智,韩云,等.中药治疗骨质疏松症的用药规律探析[J].广东药学院学报,2003,19(1):70.
[91]胡冰,张胜,邱幸凡等.骨质疏松症中医病因病机探讨[J].湖北中医杂志,2002;10(12):8-9.
[92]李小康.人之衰老,肝为先导一论肝的理论特点及其在衰老中的地位[J].天津中医学院学报,1999,18(3):3.
[93]于青琳,王文斌,韩婷.骨质疏松与老龄骨折发病率[J].中国临床康复,2003,7(21):2981.
[94]颜正华主编.中药学[M].知音出版社,823.
[95]张丰强.李岩.李晓锐.毛效军编着.现代中医临床手册[M].志远书局,2002,419.
[96]黄霞,刘杰,刘惠霞.熟地多糖对血虚模型小鼠的影响[J].中国中药杂志,2004,29(12):1168-1170.
[97]颜正华主编.中药学[M].知音出版社,899-900.
[98]颜正华主编.中药学[M].知音出版社,755.
[99]巢志茂.国外医学.中医中药分册.,1992,4(1):61.
[100]刘世昌,等.四大怀药对小鼠血液中谷胱甘肽过氧化物酶活性和过氧化脂质含量的影响[J].中药材1991,14(4):39.
[101]王旭,朱垚,陆明.周仲瑛“瘀热致消”学术思想探究[J].中医杂志,2009年3月50卷第3期.206-207.
[102]陈涛.山茱萸水提液对骨质疏松模型小鼠骨形态学影响.天津药学,2003,8(15):5.
[103]马克昌,高子范,张灵菊,等.骨碎补对大白鼠骨质疏松模型的影响[J].中医正骨,1992,4(4):3-4.
[104]喻永新,冯新送,刘庆思,等.骨质疏松的防治研究近况[J].中国中医骨伤科杂志,2001,9(2):62-65.
[105]高昌琨.怀牛膝对维甲酸所致大鼠骨质疏松防治作用的实验研究[J].基层中药杂志,2001,15(2),9-10.
[106]赵成国.鬼箭羽提取物抗心肌缺血的实验研究[D].黑龙江中医药大学,2007.
[107]Yoshikawa H. C A,1969,70:18809a.
[108]姚建峰,许鹏,郭雄,等.谷康泰灵对骨质疏松模型大鼠骨形成和骨吸收功能的影响[J].中国骨质疏松杂志,2002,8(3):255-257.
[109]马涛,崔燎,吴铁,等.老年大鼠含淫羊霍血清对成骨细胞的增殖与分化的影响[J].中国骨质疏松杂志,2002,8(1):55-57,60.
[110]肖建德,阎德文,刘景芳,等.中药龟丝补骨片对绝经后早期妇女性激素和钙调节激素的影响[J].中国骨质疏松杂志,2002,8(3):258-262.
[111]支会英,李恩.补肾方药对去卵巢大鼠骨质疏松的骨组织ER表达的影响[J].中国中医基础医学杂志,2001,7(4):41-44.
[112]鞠大宏,张春英,王安民,等.温补肾阳方对去卵巢所致骨质疏松大鼠工L1和工L6活性的影响[J].中国中医基础医学杂志,2000,6(10):59.