独活寄生汤颗粒治疗肝肾亏虚型膝骨关节炎临床疗效观察
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摘要
原发性膝骨性关节炎是中老年最常发生的慢性关节疾病,主要表现为缓慢发展的膝关节疼痛,功能障碍,劳累或受凉后加重,其病理特征是膝关节软骨发生退行性病变,并有骨赘形成,骨赘形成是修复和再生的结果。随着人口老龄化,膝骨性关节炎的发病率呈明显上升趋势,许多患者因关节功能障碍失去活动能力,严重影响中老年人的正常工作和生活,给个人、家庭和社会带来沉重的负担,随着人口老龄化程度的加深,这一问题将会愈加突出。1999年世界卫生组织把骨性关节炎与心血管疾病及癌症列为危害人类健康的三大杀手,将2000～2010年定为“骨与关节十年”。
膝关节OA的整个疾病过程不仅影响到关节软骨,还涉及关节边缘骨质及整个关节。但是其基本改变是以关节面软骨退变为中心,逐步累及整个关节,包括软骨下骨质、关节囊、韧带、滑膜以及关节周围肌肉组织等。随着年龄的增加,软骨下滋养血管数量下降,软骨生理、生化异常改变,软骨基质蛋白多糖生物合成和分解异常,软骨细胞不能合成正常的具有长链结构的透明质酸和聚氨基葡萄糖,由此产生的短链蛋白多糖聚合物从胶原网状结构中逸出,导致关节软骨局部软化、失去弹性、磨损及结构破坏,继发性反应包括超氧化物自由基、胶原酶和磷脂酶的激活,也导致软骨的损伤并引发关节相邻骨骼的OA反应。此外,软骨退变或者受到损伤后,首先是胶原纤维支架的分离,退变或者受到损伤软骨承受应力的能力下降,导致软骨下骨承受相对较多的应力而发生微骨折。修复后的骨组织失去正常的弹性,引发关节软骨的进一步损伤,伴随着软骨下骨质增生,容易发生软骨剥脱,从而使关节逐渐畸形、破坏,最终发生膝关节解剖学异常和功能障碍。
对于该病的治疗目前方法很多,但尚无根治的方法,常用的治疗方法为服用非甾体消炎药消炎止痛。非甾体消炎药长期服用往往引起药物副作用,且治疗效果不理想,中医中药对该病的诊断治疗有其自身的优势。
中医学认为,膝骨性关节炎的发生主要是由于肝肾虚损,筋脉失养,加之寒湿侵袭,阻滞经络,脉络瘀阻,关节失去濡润所致。原发性膝骨性关节炎以肝肾亏虚、筋骨俱损为本,寒湿阻滞经络为标,治疗当以散寒除湿通络、补益肝肾为主。独活寄生汤出自《备急千金要方》,原为治疗“肾气虚弱,卧冷湿之地当风而得腰背冷痛,或为偏枯冷痹缓弱疼痛,或腰痛挛脚重痹”而设。近代主要用该方治疗痹证日久正虚邪实者,如慢性关节炎、慢性腰腿痛等。
独活寄生汤取自千金要方,方中以独活为君,取其理伏风,善祛下焦与筋骨间之风寒湿邪。伍以细辛发散阴经风寒,搜剔筋骨风湿而止痛;防风祛风邪以胜湿;秦艽除风湿而舒筋;寄生、杜仲、牛膝兼补肝肾;当归、川芎、地黄、白芍养血又兼活血;人参、茯苓补气健脾;肉桂温通血脉。甘草调和诸药。综合全方,祛邪扶正,标本兼顾,可使血气足而风湿除,肝肾强而痹痛愈。诸药合用共奏补益肝肾,祛风除湿、舒筋活血通络止痛之效。现代药理研究,秦艽、独活有抗炎、镇痛作用,肉桂、防风有解热镇痛作用,当归、川芎除镇痛作用外有改善微循环的作用。
目前对独活寄生汤治疗膝骨关节炎的研究主要集中于实验研究,临床研究多为简单的临床观察,有的研究没有严格的诊断标准和纳入标准,有的研究采用的是比较简单,可信度不高的疗效判断标准,所以研究层次不高,不能充分论证独活寄生汤治疗膝骨关节炎的确切疗效。针对存在的问题和不足,本研究目的拟在严格的临床研究结果上,充分论证独活寄生汤颗粒治疗肝肾亏虚型膝骨关节炎的临床疗效,为中医中药治疗膝骨关节炎提供临床参考依据。
1、方法
本研究采用严格的入选标准,选择53例符合诊断标准、纳入标准和排除标准的膝骨关节炎患者,给予独活寄生汤颗粒剂口服治疗,治疗3个月为研究时间,采用目前国内大型临床研究采用的膝骨关节炎疗效评价标准,分别在治疗1、2、3月观察患者对关节炎的总体评价(记分法),医生对关节炎的总体评价(记分法),膝关节疼痛程度(VAS视觉模拟评价标尺法),西安大略麦马斯特大学骨性关节炎指数可视化量表(WOMAC)关节炎指数,分别比较治疗前后指标变化情况,较系统客观评价独活寄生汤颗粒治疗膝骨关节炎的临床疗效。
2、结果
2.1研究显示,治疗前患者对关节炎的总体评分较高,治疗1月后,患者对关节炎的总体评分比治疗前有所降低,但与治疗前比较评分的差别没有显著性意义;治疗2个月后,评分进一步降低,与治疗前比较,差异显著;治疗3个月后,评分明显降低,差异非常显著。患者对关节炎的总体评估较治疗前改善了41.2%。
2.2研究显示,治疗前医生对关节炎的总体评分较高,治疗1后月,医生对关节炎的总体评分比治疗前有所降低,但与治疗前比较评分的差别没有显著性意义;治疗2个月后,评分进一步降低,与治疗前比较,差异显著;治疗3个月后,评分明显降低,差异非常显著。医生对关节炎的总体评估较治疗前改善了35.3%。
2.3研究显示,治疗前患者对膝关节疼痛程度的总体评分较高,治疗1后月,患者对膝关节疼痛的总体评分比治疗前有所降低,但与治疗前比较评分的差别没有显著性意义;治疗2个月后,评分进一步降低,与治疗前比较,差异显著;治疗3个月后,评分明显降低,差异非常显著。患者对膝关节疼痛总体评估较治疗前改善了62.5%。
2.4结果显示,治疗前平均WOMAC关节指数评分高,治疗1后月,WOMAC指数的评分比治疗前有所降低,但与治疗前比较评分的差别没有显著性意义;治疗2个月后,评分进一步降低,与治疗前比较,差异显著;治疗3个月后,评分明显降低,差异非常显著。WORAC指数治疗后较治疗前改善了57.8%。
2.5结果显示,治疗1个月后,有2名患者达到病情改善标准,有50例患者病情无明显变化,有1患者病情有严重的趋势;治疗2月后,28例患者病情改善,25例无明显变化,无患者病情恶化;治疗3个月后,41例患者病情改善,12例病情不变,无患者病情恶化,治疗结束时,总改善率达到77%。
3、结论
3.1独活寄生汤颗粒明显改善患者对肝肾亏虚型膝骨关节炎的总体评价。
膝骨关节炎是由于随年龄增长,长期劳损,肝肾不足是病机之本,而肝肾不足的补益,需要很长时间,所以治疗2个月,才出现有统计学意义的疗效,随着治疗时间的延长,肝肾日渐得补,故患者的疼痛肿胀,功能受限等逐渐好转,到治疗结束时,与治疗前比较,差异非常显著。骨关节炎是一个伴随终身的疾病,骨质的破坏,关节的畸形从理论上讲是不可逆转的,治疗的目的在于缓解症状,减慢膝骨关节炎的发展过程,改善患者的功能,从而提高生活质量,所以治疗是一个长期的过程,3个月的治疗只是开始的一小部分,还需要继续治疗。
3.2独活寄生汤颗粒可以明显改善医生对肝肾亏虚型膝骨关节炎的总体评价。
医生对膝骨关节炎的评价更加客观和全面,可以较充分反应治疗的效果,在本研究中,医生对关节炎的总体评价和患者对关节炎的总体评价是一致的。治疗一个月后,部分病人疗效较明显,入组时病情比较轻的患者疗效较快,关节疼痛、功能较快恢复,行走、下蹲、坐等动作完成情况好转,大大提高了患者的信心和生存质量,但病情较重的患者改善较慢,部分患者服药一个月后也无明显变化,而治疗2个月后,由于疼痛和功能的改善出现差异,患者更加配合治疗,进步也较快,所以医生评价也出现有统计学意义的改善,治疗结束时,大部分患者疼痛缓解,功能提高,相信随着治疗的延长,肝肾不足的症状逐渐减轻,患者和医生对关节炎的总体评价还会有更多改善。
3.3独活寄生汤颗粒可以有效缓解肝肾亏虚型膝关节疼痛。
肾主骨、肝主筋,人至中年后,肝肾渐亏,筋骨失养,不荣则痛;加之风寒湿邪乘虚侵袭留驻关节,或跌仆扭伤,导致经脉瘀滞,不通则痛。治疗一个月时,患者的膝关节静息痛好转较明显,而膝关节活动痛好转不明显,所以膝关节疼痛的VAS评分无明显改善,到治疗2个月后,不仅静息痛,而且活动痛都得到改善,所以VAS评分有统计学差异,治疗结束时,疗效进一步显现。这也提示我们,独活寄生汤的止痛效果,并不像非甾体抗炎药一样是通过直接抑制炎症因子来达到的,而是通过更上游的调控作用,减少了炎症因子的产生,通过补肝肾,强壮了筋骨,通过祛风湿,通畅了痹阻的关节筋脉,筋骨强壮、筋脉通畅,所以“通则不痛”、“荣则不痛”,膝关节疼痛随着补肾祛风湿而逐渐改善,最终达到62.5%的改善度。
3.4独活寄生汤颗粒可以明显改善WOMAC关节指数评分。
治疗1个月后,WOMAC评分有降低,但没有统计学差异,直到2个月后,才出现明显改善,3个月后疗效最好,WOMAC的变化也说明对膝骨关节炎的治疗,是一个长期的过程,正如前述,本组患者的膝关节炎,都是由于肝肾不足,风湿痹阻所导致的,此风、此湿都是内风、内湿,都和肝肾不足有关,肝肾不足一和年龄的增加发生退化有关,一和关节的长期劳损有关,所以要逆转肝肾亏虚,也是一个长期的过程,随着肝肾得补,关节日益强壮,气血得补,关节得到营养,不通不荣得到改善,所以患者疼痛、僵硬减轻。我们可以看到,WOMAC评价内容中,有关关节疼痛的仅有5条,关节僵硬的仅有2条,而关于关节功能的达到13条之多,由于关节强健、疼痛减轻,膝关节的功能明显提高,患者能改善站立、行走、上下楼梯、穿脱鞋袜,甚至能外出购物,能完成部分或全部家务,生活质量明显改善,所以WOMAC评分才达到最大改善。独活寄生汤不是止痛消肿药,而是补肾药,这也告诉我们,中医治疗骨关节炎一定要辨证论治,一定要针对病因病机进行治疗,中医是治本,不是治标。
3.5独活寄生汤颗粒治疗肝肾不足型肝肾亏虚型膝骨关节炎疗效肯定。
独活寄生汤颗粒治疗骨关节炎的总改善率达到77%,整个治疗过程我们发现,约一半患者在治疗第2个月结束时才达到明显疗效,大部分患者是在治疗后3个月才到达病情改善的,与非甾体抗炎药相比,独活寄生汤颗粒的起效较慢,但治疗中没有发现明显不良反应,患者耐受性好,而且,独活寄生汤不仅能止痛,更能改善患者的关节功能,提高生存质量。
Primary Knee Osteoarthritis(KOA) is a chronic joint disease which occurs most frequently among middle-aged and old people,its main symptoms including knee joint pain,dysfunction and aggravation after tire or catching cold.Its pathological features are degenerative pathological changes of knee joint cartilages and osteophyte which is the result of recovery and regeneration. With the aging of population,the incidence of KOA is rising.Many patients lose movement ability for joint dysfunction.It seriously affects middle-aged and old people' s normal life and work,bringing heavy burden to individuals, families and society.This problem will be more prominent with the aging progress.In 1999,Osteoarthritis(OA),together with cardiovascular diseases and cancer,is listed as three killers of human health by WHO and 2000-2010 are designated as "ten years of bones and joints".
KOA affects not only the joint cartilage but also bone substances at joint brims and even the whole joint.However,the basic change takes joint surface cartilage as the center and gradually affects the whole joint,including subchondral bone substance,joint capsule,ligament,bursa and the peri-joint musculature.With aging,subchondral nutrient vessels drop in number, cartilage has abnormal physiological and biochemical changes,cartilage polysaccharide protein organisms compose and decompose abnormally,cartilage cells can' t compose normal and long-chain-structured Hyaloplasm Acid(HA) and Glucosaminoglycan(GAG) and the short-chain-structured Protein-polysaccharide polymers transgress from the collagenous reticular structure.Therefore the joint cartilages intenerate locally,lose flexibility,fret and the structure ruins.The secondary effects include the activation of superoxide free radical,collagen enzyme and phospholipase and injury of cartilages and OA effect of bones near joints.Besides,after the degeneration or injury of cartilages,collagen fiber framework severs first, the supporting ability of degenerated or injured cartilage drops,subchondral bone endures excessive stress and has micro-fracture.The rehabilitated osseous tissue loses the normal flexibility and causes further injury in joint cartilages and subchondral hyperosteogeny.Cartilages may easily exfoliate and joints may develop into abnormality and wreckage,finally resulting in knee joint anatomical abnormality and dysfunction.
At present,there are many ways to treat this disease,but no radical cure. Commonly used treatment includes diminishing inflammation and pain with non-steroid anti-inflammatory drugs and promoting blood circulation, removing blood stasis and activating channels and meridians with Chinese Materia Medica.Long-term administration of non-steroid anti-inflammatory drugs frequently causes side effects and the curative effect is not desirable. For the diagnosis and treatment of this disease,Chinese Medicine and Chinese Materia Medica have advantages.
From angle of Chinese Medicine,ROA is mainly caused by liver and kidney deficiency,loss of nutrition in tendons and meridians,coldness and dampness invasion,meridian and channel blockage and stagnation and the loss of nutrition in joints.The Primary ROA takes deficiency of liver,kidney, tendons and bones as the root and meridian and channel blockage by coldness and dampness as signs.The treatment principle is to disperse coldness and dampness,activate the channels and reinforce kidney.Angelicae Pubescentis and Loranthi Decoction is from Valuable Prescriptions for Emergencies which originally treats kidney-qi deficiency,cold and pain in back and legs for wind invasion and staying in cold and damp places,to treat the hemiplegia, arthralgia spasm with chill,weakness and pain or to treat the back pain,foot sprain and severe arthralgia spasm.Nowadays,it' s used to treat the long-term arthralgia spasm and asthenia healthy qi and sthenia pathogenic factor syndrome,like chronic arthritis and chronic back and leg pain.
Angelicae Pubescentis and Loranthi Decoction is from Valuable Prescriptions for Emergencies.As the major element of the prescription, Angelicae Pubescentis cures the potential wind evil and is good at demolishing the wind cold and dampness evil between Lower Energizer and bones and muscles. Asiasarum can disperse wind cold and diminish rheumatism in bones and muscles so as to relieve pain.Saposhnikoviae can prevent wind evil and dampness. Largeleaf gentian root can relieve rheumatism and stretch the tendons. Loranthi,eucommia bark and achyranthis can reinforce liver and kidney. Angelica,ligustici rhizome,rehmannia,paeoniae alba can nourish and promote blood circulation.Ginseng and hoelen can reinforce qi and spleen.Cortex cinnamon can warm the biood vessels.Licorice root ameliorates all elements. The whole prescription can diminish the evil factors,support the healthy qi, take care of both root and signs of diseases,invigorate blood and qi and diminish rheumatism,reinforce liver and kidney and cure arthralgia spasm and pain.The combination of all elements can reinforce liver and kidney,diminish wind evil and dampness,stretch tendons and promote blood circulation and collaterals to stop pain.Modern pharmacology research shows largeleaf gentian root and angelicae pubescentis have anti-inflammatory and analgesic function.Ramulus cinnamoni and saposhnikoviae can relieve fever and pain. Angelica and ligustici rhizoma can improve the microcirculation besides relieving pain.
The researches on KOA treatment with Angelicae Pubescentis and Loranthi Decoction are mainly experimental.The clinical researches are mainly simple observations.Some don't take strict diagnosis and inclusion standard and some take comparatively simple curative efficacy judgment criteria with low reliability.Therefore these are low-level researches and can't fully prove the accurate curative efficacy of Angelicae Pubescentis and Loranthi Decoction.Considering the problems and defects,based on strict clinical research results,this research intends to fully prove the clinical efficacy of Angelicae Pubescentis and Loranthi Decoction in KOA treatment so as to provide clinical reference for Chinese Medicine and Chinese Materia Medica treatment of KOA.
1.Methods
This research takes strict inclusion standard and selects 53 KOA patients consistent with diagnostic,incIusion and preclusion standards.They take Angelicae Pubescentis and Loranthi Decoction granules orally for 3 months. The author adopts KOA curative efficacy evaluation index used in large-scale clinical researches in the country and at the end of the first,second and third month records patients' and doctors' general evaluation(grading) of arthritis,knee joint pain degree(VAS Visual Analogue Scale) and WOMAC arthritis index.Compare the index changes before and after the treatment and give objective and systematic evaluation.
2.Result
2.1 The research shows that patients' general grading of arthritis is high and it drops after one month' s treatment,but there' s no significant difference.The grading drops further at the end of the second month and there' s significant difference.After three months,the grading obviously drops and the difference is quite prominent and significant.Patients' general grading of arthritis improves at 41.2%compared with that before treatment.
2.2 Research shows doctors' general grading of arthritis is high and it drops after one month' s treatment,but there' s no significant difference.The grading drops further at the end of the second month and there' s significant difference.After three months,the grading obviously drops and the difference is quite prominent and significant.Patients' general grading of arthritis improves at 35.3%compared with that before treatment.
2.3 The research shows that patients' general grading of knee pain is high and it drops after one month' s treatment,but there' s no significant difference.The grading drops further at the end of the second month and there's significant difference.After three months,the grading obviously drops and the difference is quite prominent and significant.Patients' general grading of knee joint pain improves at 62.5%compared with that before treatment.
2.4 The result shows the average WOMAC joint index grading is high before treatment and it drops after one month's treatment,but there's no significant difference.The grading drops further at the end of the second month and there's significant difference.After three months,the grading obviously drops and the difference is quite prominent and significant.The WOMAC index grading improves at 57.8%compared with that before treatment.
2.5 The result shows 2 patients' condition reaches the improvement standard, 50 patients' condition doesn't have obvious change,1 patient' s condition worsens after 1 month' s treatment;28 patients' condition improves,25 patients' condition doesn't have obvious change,and no patient's condition worsens after 2 months' treatment;41 patients' condition improves,12 patients' condition doesn't have change and no patient' s condition worsens after 3 months' treatment.At the end of the treatment, the general improvement rate is 77%.
3.Conclusion
3.1 Angelicae Pubescentis and Loranthi Decoction Granules Obviously Improves Patients' General Grading of KOA
Because of long-term strain,the liver and kidney deficiency,which needs a long period of time for treatment,causes KOA.Statistical significance in curative efficacy occurs only after two months' treatment.With the extending of treatment,liver and kidney are reinforced,so the patients' pain and swelling and limited function improve.At the end of the treatment,the difference is significant compared with that before treatment.Osteoarthritis is a lifelong disease.As the bone substance is damaged,so theoretically the joint abnormality is not reversible.The treatment purpose is to relieve symptoms,slow the KOA development,and improve the patients' function so as to improve lift quality.Therefore the treatment takes a long period of time.3-month treatment is just a small part and further treatment is needed.
3.2 Angelicae Pubescentis and Loranthi Decoction Granules Obviously Improves Doctors' General Grading of KOA
Doctors' evaluation of KOA tends to be more objective and complete which fully reflects the curative efficacy.In this research,the doctors' and patients' general grading of arthritis are consistent.After one-month treatment,part of the patients have obvious curative efficacy.Those with lighter disease condition recover more quickly in joint pain and function improvement and completion of walking,squatting and sitting,etc.These greatly enhance the patients' confidence and life quality.Those patients with severe condition improve slowly.Part of the patients don' t have obvious changes after one month' s medicine administration.After two months' treatment,because of improvement of pain relieving and function,patients cooperate with treatment more actively and make more progress,so the doctors' evaluation has statistical significance.At the end of the treatment, most patients' pain relieves and function improves.With the lengthening of treatment,liver and kidney deficiency will gradually lessen and patients' and doctors' general grading of arthritis will have more improvement.
3.3 Angelicae Pubescentis and Loranthi Decoction Granules Effectively Relieve Knee Joint Pain
Kidney is in charge of bones and liver of tendons.Reaching middle age, people have deficient liver and kidney.The tendons and bones lose nutrition and so pain occurs.If wind and dampness evil attacks and stays at joints or tumbling and spraining occur,artery and vessel stagnation will be caused. Stagnation of qi and blood may bring about pain.At the end of the first month' s treatment,the knee joint rest pain improves obviously,but the activity pain improvement is not obvious.So the VAS grading of knee joint pain has no obvious improvement.This reminds us that the pain relieving effect of Angelicae Pubescentis and Loranthi Decoction is not achieved by directly inhibiting the inflammation factors like non-steroid anti-inflammatory drugs. It lessens the production of inflammatory factors with upstream controlling. By reinforcing the kidney and liver,it strengthens tendons and bones.By diminishing rheumatism,it smoothes the joints and tendons blocked by arthralgia spasm.Strong tendons and bones and smooth muscles and vessels don' t bring about pain.With reinforcing kidney and diminishing rheumatism, knee joint pain will gradually relieve and finally the improvement rate will reach 62.5%.
3.4 Angelicae Pubescentis and Loranthi Deeoction Granules Obviously Improves WOMAC Joint Index Grading
After one month' s treatment,WOMAC grading lowers but doesn't have statistical significance.Only after two months does it improve obviously. At the end of the third month,the curative efficacy is the best.WOMAC changes shows KOA treatment is a long-term process.As mentioned above,the KOA in this group is caused by liver and kidney deficiency and rheumatic arthralgia blockage.These are internal wind and dampness and related to liver and kidney deficiency which is related to aging-caused degeneration and long-term joint strain.So to reverse the liver and kidney deficiency takes long time.If liver and kidney are reinforced,joints are stronger;if qi and blood are reinforced, the joints obtain nutrition.Thus the pain and stiffness of patients are lessened.Because of strong joints and relieved pain,the knee joint function improves obviously.Patients make progress in standing,walking,going up and down the stairs,putting on and taking off shoes and socks,going out for shopping,doing part of or all the housework and improving life quality, therefore WOMAC grading reaches the greatest improvement level.Angelicae Pubescentis and Loranthi Decoction is not to diminish pain and swelling.It's a medicine to reinforce kidney.This tells us syndrome differentiation is essential when using Chinese Medicine to treat osteoarthritis.Treatment must be undertaken according to etiological factors and pathogenesis.Chinese Medicine is to cure the root of diseases,not the signs.
3.5 Angelicae Pubescentis and Loranthi Decoction Granule Has Definite Curative Efficacy in KOA Treatment
The general improvement rate of Angelicae Pubescentis and Loranthi Decoction Granule's treatment of KOA is 77%.Because of the clinical efficacy of non-steroid anti-inflammatory drugs and articular cartilage supplements in many researches,we discover from the whole curative process that half the patients have obvious improvement only after 2 months' treatment and most patients after 3 months.Compared with non-steroids,Angelicae Pubescentis and Loranthi Decoction granules exert function slowlier but no adverse reaction is found in treatment.The patients have good tolerance.Angelicae Pubescentis and Loranthi Decoction can not only stop pain,but also improve the joint function of patients so as to improve the life quality.
膝关节OA的整个疾病过程不仅影响到关节软骨,还涉及关节边缘骨质及整个关节。但是其基本改变是以关节面软骨退变为中心,逐步累及整个关节,包括软骨下骨质、关节囊、韧带、滑膜以及关节周围肌肉组织等。随着年龄的增加,软骨下滋养血管数量下降,软骨生理、生化异常改变,软骨基质蛋白多糖生物合成和分解异常,软骨细胞不能合成正常的具有长链结构的透明质酸和聚氨基葡萄糖,由此产生的短链蛋白多糖聚合物从胶原网状结构中逸出,导致关节软骨局部软化、失去弹性、磨损及结构破坏,继发性反应包括超氧化物自由基、胶原酶和磷脂酶的激活,也导致软骨的损伤并引发关节相邻骨骼的OA反应。此外,软骨退变或者受到损伤后,首先是胶原纤维支架的分离,退变或者受到损伤软骨承受应力的能力下降,导致软骨下骨承受相对较多的应力而发生微骨折。修复后的骨组织失去正常的弹性,引发关节软骨的进一步损伤,伴随着软骨下骨质增生,容易发生软骨剥脱,从而使关节逐渐畸形、破坏,最终发生膝关节解剖学异常和功能障碍。
对于该病的治疗目前方法很多,但尚无根治的方法,常用的治疗方法为服用非甾体消炎药消炎止痛。非甾体消炎药长期服用往往引起药物副作用,且治疗效果不理想,中医中药对该病的诊断治疗有其自身的优势。
中医学认为,膝骨性关节炎的发生主要是由于肝肾虚损,筋脉失养,加之寒湿侵袭,阻滞经络,脉络瘀阻,关节失去濡润所致。原发性膝骨性关节炎以肝肾亏虚、筋骨俱损为本,寒湿阻滞经络为标,治疗当以散寒除湿通络、补益肝肾为主。独活寄生汤出自《备急千金要方》,原为治疗“肾气虚弱,卧冷湿之地当风而得腰背冷痛,或为偏枯冷痹缓弱疼痛,或腰痛挛脚重痹”而设。近代主要用该方治疗痹证日久正虚邪实者,如慢性关节炎、慢性腰腿痛等。
独活寄生汤取自千金要方,方中以独活为君,取其理伏风,善祛下焦与筋骨间之风寒湿邪。伍以细辛发散阴经风寒,搜剔筋骨风湿而止痛;防风祛风邪以胜湿;秦艽除风湿而舒筋;寄生、杜仲、牛膝兼补肝肾;当归、川芎、地黄、白芍养血又兼活血;人参、茯苓补气健脾;肉桂温通血脉。甘草调和诸药。综合全方,祛邪扶正,标本兼顾,可使血气足而风湿除,肝肾强而痹痛愈。诸药合用共奏补益肝肾,祛风除湿、舒筋活血通络止痛之效。现代药理研究,秦艽、独活有抗炎、镇痛作用,肉桂、防风有解热镇痛作用,当归、川芎除镇痛作用外有改善微循环的作用。
目前对独活寄生汤治疗膝骨关节炎的研究主要集中于实验研究,临床研究多为简单的临床观察,有的研究没有严格的诊断标准和纳入标准,有的研究采用的是比较简单,可信度不高的疗效判断标准,所以研究层次不高,不能充分论证独活寄生汤治疗膝骨关节炎的确切疗效。针对存在的问题和不足,本研究目的拟在严格的临床研究结果上,充分论证独活寄生汤颗粒治疗肝肾亏虚型膝骨关节炎的临床疗效,为中医中药治疗膝骨关节炎提供临床参考依据。
1、方法
本研究采用严格的入选标准,选择53例符合诊断标准、纳入标准和排除标准的膝骨关节炎患者,给予独活寄生汤颗粒剂口服治疗,治疗3个月为研究时间,采用目前国内大型临床研究采用的膝骨关节炎疗效评价标准,分别在治疗1、2、3月观察患者对关节炎的总体评价(记分法),医生对关节炎的总体评价(记分法),膝关节疼痛程度(VAS视觉模拟评价标尺法),西安大略麦马斯特大学骨性关节炎指数可视化量表(WOMAC)关节炎指数,分别比较治疗前后指标变化情况,较系统客观评价独活寄生汤颗粒治疗膝骨关节炎的临床疗效。
2、结果
2.1研究显示,治疗前患者对关节炎的总体评分较高,治疗1月后,患者对关节炎的总体评分比治疗前有所降低,但与治疗前比较评分的差别没有显著性意义;治疗2个月后,评分进一步降低,与治疗前比较,差异显著;治疗3个月后,评分明显降低,差异非常显著。患者对关节炎的总体评估较治疗前改善了41.2%。
2.2研究显示,治疗前医生对关节炎的总体评分较高,治疗1后月,医生对关节炎的总体评分比治疗前有所降低,但与治疗前比较评分的差别没有显著性意义;治疗2个月后,评分进一步降低,与治疗前比较,差异显著;治疗3个月后,评分明显降低,差异非常显著。医生对关节炎的总体评估较治疗前改善了35.3%。
2.3研究显示,治疗前患者对膝关节疼痛程度的总体评分较高,治疗1后月,患者对膝关节疼痛的总体评分比治疗前有所降低,但与治疗前比较评分的差别没有显著性意义;治疗2个月后,评分进一步降低,与治疗前比较,差异显著;治疗3个月后,评分明显降低,差异非常显著。患者对膝关节疼痛总体评估较治疗前改善了62.5%。
2.4结果显示,治疗前平均WOMAC关节指数评分高,治疗1后月,WOMAC指数的评分比治疗前有所降低,但与治疗前比较评分的差别没有显著性意义;治疗2个月后,评分进一步降低,与治疗前比较,差异显著;治疗3个月后,评分明显降低,差异非常显著。WORAC指数治疗后较治疗前改善了57.8%。
2.5结果显示,治疗1个月后,有2名患者达到病情改善标准,有50例患者病情无明显变化,有1患者病情有严重的趋势;治疗2月后,28例患者病情改善,25例无明显变化,无患者病情恶化;治疗3个月后,41例患者病情改善,12例病情不变,无患者病情恶化,治疗结束时,总改善率达到77%。
3、结论
3.1独活寄生汤颗粒明显改善患者对肝肾亏虚型膝骨关节炎的总体评价。
膝骨关节炎是由于随年龄增长,长期劳损,肝肾不足是病机之本,而肝肾不足的补益,需要很长时间,所以治疗2个月,才出现有统计学意义的疗效,随着治疗时间的延长,肝肾日渐得补,故患者的疼痛肿胀,功能受限等逐渐好转,到治疗结束时,与治疗前比较,差异非常显著。骨关节炎是一个伴随终身的疾病,骨质的破坏,关节的畸形从理论上讲是不可逆转的,治疗的目的在于缓解症状,减慢膝骨关节炎的发展过程,改善患者的功能,从而提高生活质量,所以治疗是一个长期的过程,3个月的治疗只是开始的一小部分,还需要继续治疗。
3.2独活寄生汤颗粒可以明显改善医生对肝肾亏虚型膝骨关节炎的总体评价。
医生对膝骨关节炎的评价更加客观和全面,可以较充分反应治疗的效果,在本研究中,医生对关节炎的总体评价和患者对关节炎的总体评价是一致的。治疗一个月后,部分病人疗效较明显,入组时病情比较轻的患者疗效较快,关节疼痛、功能较快恢复,行走、下蹲、坐等动作完成情况好转,大大提高了患者的信心和生存质量,但病情较重的患者改善较慢,部分患者服药一个月后也无明显变化,而治疗2个月后,由于疼痛和功能的改善出现差异,患者更加配合治疗,进步也较快,所以医生评价也出现有统计学意义的改善,治疗结束时,大部分患者疼痛缓解,功能提高,相信随着治疗的延长,肝肾不足的症状逐渐减轻,患者和医生对关节炎的总体评价还会有更多改善。
3.3独活寄生汤颗粒可以有效缓解肝肾亏虚型膝关节疼痛。
肾主骨、肝主筋,人至中年后,肝肾渐亏,筋骨失养,不荣则痛;加之风寒湿邪乘虚侵袭留驻关节,或跌仆扭伤,导致经脉瘀滞,不通则痛。治疗一个月时,患者的膝关节静息痛好转较明显,而膝关节活动痛好转不明显,所以膝关节疼痛的VAS评分无明显改善,到治疗2个月后,不仅静息痛,而且活动痛都得到改善,所以VAS评分有统计学差异,治疗结束时,疗效进一步显现。这也提示我们,独活寄生汤的止痛效果,并不像非甾体抗炎药一样是通过直接抑制炎症因子来达到的,而是通过更上游的调控作用,减少了炎症因子的产生,通过补肝肾,强壮了筋骨,通过祛风湿,通畅了痹阻的关节筋脉,筋骨强壮、筋脉通畅,所以“通则不痛”、“荣则不痛”,膝关节疼痛随着补肾祛风湿而逐渐改善,最终达到62.5%的改善度。
3.4独活寄生汤颗粒可以明显改善WOMAC关节指数评分。
治疗1个月后,WOMAC评分有降低,但没有统计学差异,直到2个月后,才出现明显改善,3个月后疗效最好,WOMAC的变化也说明对膝骨关节炎的治疗,是一个长期的过程,正如前述,本组患者的膝关节炎,都是由于肝肾不足,风湿痹阻所导致的,此风、此湿都是内风、内湿,都和肝肾不足有关,肝肾不足一和年龄的增加发生退化有关,一和关节的长期劳损有关,所以要逆转肝肾亏虚,也是一个长期的过程,随着肝肾得补,关节日益强壮,气血得补,关节得到营养,不通不荣得到改善,所以患者疼痛、僵硬减轻。我们可以看到,WOMAC评价内容中,有关关节疼痛的仅有5条,关节僵硬的仅有2条,而关于关节功能的达到13条之多,由于关节强健、疼痛减轻,膝关节的功能明显提高,患者能改善站立、行走、上下楼梯、穿脱鞋袜,甚至能外出购物,能完成部分或全部家务,生活质量明显改善,所以WOMAC评分才达到最大改善。独活寄生汤不是止痛消肿药,而是补肾药,这也告诉我们,中医治疗骨关节炎一定要辨证论治,一定要针对病因病机进行治疗,中医是治本,不是治标。
3.5独活寄生汤颗粒治疗肝肾不足型肝肾亏虚型膝骨关节炎疗效肯定。
独活寄生汤颗粒治疗骨关节炎的总改善率达到77%,整个治疗过程我们发现,约一半患者在治疗第2个月结束时才达到明显疗效,大部分患者是在治疗后3个月才到达病情改善的,与非甾体抗炎药相比,独活寄生汤颗粒的起效较慢,但治疗中没有发现明显不良反应,患者耐受性好,而且,独活寄生汤不仅能止痛,更能改善患者的关节功能,提高生存质量。
Primary Knee Osteoarthritis(KOA) is a chronic joint disease which occurs most frequently among middle-aged and old people,its main symptoms including knee joint pain,dysfunction and aggravation after tire or catching cold.Its pathological features are degenerative pathological changes of knee joint cartilages and osteophyte which is the result of recovery and regeneration. With the aging of population,the incidence of KOA is rising.Many patients lose movement ability for joint dysfunction.It seriously affects middle-aged and old people' s normal life and work,bringing heavy burden to individuals, families and society.This problem will be more prominent with the aging progress.In 1999,Osteoarthritis(OA),together with cardiovascular diseases and cancer,is listed as three killers of human health by WHO and 2000-2010 are designated as "ten years of bones and joints".
KOA affects not only the joint cartilage but also bone substances at joint brims and even the whole joint.However,the basic change takes joint surface cartilage as the center and gradually affects the whole joint,including subchondral bone substance,joint capsule,ligament,bursa and the peri-joint musculature.With aging,subchondral nutrient vessels drop in number, cartilage has abnormal physiological and biochemical changes,cartilage polysaccharide protein organisms compose and decompose abnormally,cartilage cells can' t compose normal and long-chain-structured Hyaloplasm Acid(HA) and Glucosaminoglycan(GAG) and the short-chain-structured Protein-polysaccharide polymers transgress from the collagenous reticular structure.Therefore the joint cartilages intenerate locally,lose flexibility,fret and the structure ruins.The secondary effects include the activation of superoxide free radical,collagen enzyme and phospholipase and injury of cartilages and OA effect of bones near joints.Besides,after the degeneration or injury of cartilages,collagen fiber framework severs first, the supporting ability of degenerated or injured cartilage drops,subchondral bone endures excessive stress and has micro-fracture.The rehabilitated osseous tissue loses the normal flexibility and causes further injury in joint cartilages and subchondral hyperosteogeny.Cartilages may easily exfoliate and joints may develop into abnormality and wreckage,finally resulting in knee joint anatomical abnormality and dysfunction.
At present,there are many ways to treat this disease,but no radical cure. Commonly used treatment includes diminishing inflammation and pain with non-steroid anti-inflammatory drugs and promoting blood circulation, removing blood stasis and activating channels and meridians with Chinese Materia Medica.Long-term administration of non-steroid anti-inflammatory drugs frequently causes side effects and the curative effect is not desirable. For the diagnosis and treatment of this disease,Chinese Medicine and Chinese Materia Medica have advantages.
From angle of Chinese Medicine,ROA is mainly caused by liver and kidney deficiency,loss of nutrition in tendons and meridians,coldness and dampness invasion,meridian and channel blockage and stagnation and the loss of nutrition in joints.The Primary ROA takes deficiency of liver,kidney, tendons and bones as the root and meridian and channel blockage by coldness and dampness as signs.The treatment principle is to disperse coldness and dampness,activate the channels and reinforce kidney.Angelicae Pubescentis and Loranthi Decoction is from Valuable Prescriptions for Emergencies which originally treats kidney-qi deficiency,cold and pain in back and legs for wind invasion and staying in cold and damp places,to treat the hemiplegia, arthralgia spasm with chill,weakness and pain or to treat the back pain,foot sprain and severe arthralgia spasm.Nowadays,it' s used to treat the long-term arthralgia spasm and asthenia healthy qi and sthenia pathogenic factor syndrome,like chronic arthritis and chronic back and leg pain.
Angelicae Pubescentis and Loranthi Decoction is from Valuable Prescriptions for Emergencies.As the major element of the prescription, Angelicae Pubescentis cures the potential wind evil and is good at demolishing the wind cold and dampness evil between Lower Energizer and bones and muscles. Asiasarum can disperse wind cold and diminish rheumatism in bones and muscles so as to relieve pain.Saposhnikoviae can prevent wind evil and dampness. Largeleaf gentian root can relieve rheumatism and stretch the tendons. Loranthi,eucommia bark and achyranthis can reinforce liver and kidney. Angelica,ligustici rhizome,rehmannia,paeoniae alba can nourish and promote blood circulation.Ginseng and hoelen can reinforce qi and spleen.Cortex cinnamon can warm the biood vessels.Licorice root ameliorates all elements. The whole prescription can diminish the evil factors,support the healthy qi, take care of both root and signs of diseases,invigorate blood and qi and diminish rheumatism,reinforce liver and kidney and cure arthralgia spasm and pain.The combination of all elements can reinforce liver and kidney,diminish wind evil and dampness,stretch tendons and promote blood circulation and collaterals to stop pain.Modern pharmacology research shows largeleaf gentian root and angelicae pubescentis have anti-inflammatory and analgesic function.Ramulus cinnamoni and saposhnikoviae can relieve fever and pain. Angelica and ligustici rhizoma can improve the microcirculation besides relieving pain.
The researches on KOA treatment with Angelicae Pubescentis and Loranthi Decoction are mainly experimental.The clinical researches are mainly simple observations.Some don't take strict diagnosis and inclusion standard and some take comparatively simple curative efficacy judgment criteria with low reliability.Therefore these are low-level researches and can't fully prove the accurate curative efficacy of Angelicae Pubescentis and Loranthi Decoction.Considering the problems and defects,based on strict clinical research results,this research intends to fully prove the clinical efficacy of Angelicae Pubescentis and Loranthi Decoction in KOA treatment so as to provide clinical reference for Chinese Medicine and Chinese Materia Medica treatment of KOA.
1.Methods
This research takes strict inclusion standard and selects 53 KOA patients consistent with diagnostic,incIusion and preclusion standards.They take Angelicae Pubescentis and Loranthi Decoction granules orally for 3 months. The author adopts KOA curative efficacy evaluation index used in large-scale clinical researches in the country and at the end of the first,second and third month records patients' and doctors' general evaluation(grading) of arthritis,knee joint pain degree(VAS Visual Analogue Scale) and WOMAC arthritis index.Compare the index changes before and after the treatment and give objective and systematic evaluation.
2.Result
2.1 The research shows that patients' general grading of arthritis is high and it drops after one month' s treatment,but there' s no significant difference.The grading drops further at the end of the second month and there' s significant difference.After three months,the grading obviously drops and the difference is quite prominent and significant.Patients' general grading of arthritis improves at 41.2%compared with that before treatment.
2.2 Research shows doctors' general grading of arthritis is high and it drops after one month' s treatment,but there' s no significant difference.The grading drops further at the end of the second month and there' s significant difference.After three months,the grading obviously drops and the difference is quite prominent and significant.Patients' general grading of arthritis improves at 35.3%compared with that before treatment.
2.3 The research shows that patients' general grading of knee pain is high and it drops after one month' s treatment,but there' s no significant difference.The grading drops further at the end of the second month and there's significant difference.After three months,the grading obviously drops and the difference is quite prominent and significant.Patients' general grading of knee joint pain improves at 62.5%compared with that before treatment.
2.4 The result shows the average WOMAC joint index grading is high before treatment and it drops after one month's treatment,but there's no significant difference.The grading drops further at the end of the second month and there's significant difference.After three months,the grading obviously drops and the difference is quite prominent and significant.The WOMAC index grading improves at 57.8%compared with that before treatment.
2.5 The result shows 2 patients' condition reaches the improvement standard, 50 patients' condition doesn't have obvious change,1 patient' s condition worsens after 1 month' s treatment;28 patients' condition improves,25 patients' condition doesn't have obvious change,and no patient's condition worsens after 2 months' treatment;41 patients' condition improves,12 patients' condition doesn't have change and no patient' s condition worsens after 3 months' treatment.At the end of the treatment, the general improvement rate is 77%.
3.Conclusion
3.1 Angelicae Pubescentis and Loranthi Decoction Granules Obviously Improves Patients' General Grading of KOA
Because of long-term strain,the liver and kidney deficiency,which needs a long period of time for treatment,causes KOA.Statistical significance in curative efficacy occurs only after two months' treatment.With the extending of treatment,liver and kidney are reinforced,so the patients' pain and swelling and limited function improve.At the end of the treatment,the difference is significant compared with that before treatment.Osteoarthritis is a lifelong disease.As the bone substance is damaged,so theoretically the joint abnormality is not reversible.The treatment purpose is to relieve symptoms,slow the KOA development,and improve the patients' function so as to improve lift quality.Therefore the treatment takes a long period of time.3-month treatment is just a small part and further treatment is needed.
3.2 Angelicae Pubescentis and Loranthi Decoction Granules Obviously Improves Doctors' General Grading of KOA
Doctors' evaluation of KOA tends to be more objective and complete which fully reflects the curative efficacy.In this research,the doctors' and patients' general grading of arthritis are consistent.After one-month treatment,part of the patients have obvious curative efficacy.Those with lighter disease condition recover more quickly in joint pain and function improvement and completion of walking,squatting and sitting,etc.These greatly enhance the patients' confidence and life quality.Those patients with severe condition improve slowly.Part of the patients don' t have obvious changes after one month' s medicine administration.After two months' treatment,because of improvement of pain relieving and function,patients cooperate with treatment more actively and make more progress,so the doctors' evaluation has statistical significance.At the end of the treatment, most patients' pain relieves and function improves.With the lengthening of treatment,liver and kidney deficiency will gradually lessen and patients' and doctors' general grading of arthritis will have more improvement.
3.3 Angelicae Pubescentis and Loranthi Decoction Granules Effectively Relieve Knee Joint Pain
Kidney is in charge of bones and liver of tendons.Reaching middle age, people have deficient liver and kidney.The tendons and bones lose nutrition and so pain occurs.If wind and dampness evil attacks and stays at joints or tumbling and spraining occur,artery and vessel stagnation will be caused. Stagnation of qi and blood may bring about pain.At the end of the first month' s treatment,the knee joint rest pain improves obviously,but the activity pain improvement is not obvious.So the VAS grading of knee joint pain has no obvious improvement.This reminds us that the pain relieving effect of Angelicae Pubescentis and Loranthi Decoction is not achieved by directly inhibiting the inflammation factors like non-steroid anti-inflammatory drugs. It lessens the production of inflammatory factors with upstream controlling. By reinforcing the kidney and liver,it strengthens tendons and bones.By diminishing rheumatism,it smoothes the joints and tendons blocked by arthralgia spasm.Strong tendons and bones and smooth muscles and vessels don' t bring about pain.With reinforcing kidney and diminishing rheumatism, knee joint pain will gradually relieve and finally the improvement rate will reach 62.5%.
3.4 Angelicae Pubescentis and Loranthi Deeoction Granules Obviously Improves WOMAC Joint Index Grading
After one month' s treatment,WOMAC grading lowers but doesn't have statistical significance.Only after two months does it improve obviously. At the end of the third month,the curative efficacy is the best.WOMAC changes shows KOA treatment is a long-term process.As mentioned above,the KOA in this group is caused by liver and kidney deficiency and rheumatic arthralgia blockage.These are internal wind and dampness and related to liver and kidney deficiency which is related to aging-caused degeneration and long-term joint strain.So to reverse the liver and kidney deficiency takes long time.If liver and kidney are reinforced,joints are stronger;if qi and blood are reinforced, the joints obtain nutrition.Thus the pain and stiffness of patients are lessened.Because of strong joints and relieved pain,the knee joint function improves obviously.Patients make progress in standing,walking,going up and down the stairs,putting on and taking off shoes and socks,going out for shopping,doing part of or all the housework and improving life quality, therefore WOMAC grading reaches the greatest improvement level.Angelicae Pubescentis and Loranthi Decoction is not to diminish pain and swelling.It's a medicine to reinforce kidney.This tells us syndrome differentiation is essential when using Chinese Medicine to treat osteoarthritis.Treatment must be undertaken according to etiological factors and pathogenesis.Chinese Medicine is to cure the root of diseases,not the signs.
3.5 Angelicae Pubescentis and Loranthi Decoction Granule Has Definite Curative Efficacy in KOA Treatment
The general improvement rate of Angelicae Pubescentis and Loranthi Decoction Granule's treatment of KOA is 77%.Because of the clinical efficacy of non-steroid anti-inflammatory drugs and articular cartilage supplements in many researches,we discover from the whole curative process that half the patients have obvious improvement only after 2 months' treatment and most patients after 3 months.Compared with non-steroids,Angelicae Pubescentis and Loranthi Decoction granules exert function slowlier but no adverse reaction is found in treatment.The patients have good tolerance.Angelicae Pubescentis and Loranthi Decoction can not only stop pain,but also improve the joint function of patients so as to improve the life quality.
引文
[1]李平,韩明向.肾虚络阻是骨关节炎的病机特点.中医药临床杂志,2006,18(1):89
[2]贺宪,魏春山.膝骨性关节炎的病机和防治机制探讨.山东中医杂志,2005,24(2):73
[3]徐传毅,樊粤光.肾虚血瘀与膝骨性关节炎关系初探.新中医,2002,34(3):7
[4]陈龙全,郝双阶.复方竹节参片配合穴位注射治疗膝骨性关节炎82例.陕西中医,2004,25(8):716
[5]江蓉星,汪亚强.骨关节炎的中医治疗.成都中医药大学学报,2001,24(4):11-13
[6]陈赓红.新癀片与仙骨葆合用治疗中老年骨关节退行性变的临床观察.中国中西医结合杂志,2002,22(8):586
[7]林俊宏.综合治疗膝关节骨性关节炎62例.长春中医学院学报,2002,18(1):29-30
[8]朱洪民,宁显民.黄芪桂枝五物胶囊治疗膝骨节炎临床研究.福建中医药,2002,33(3):15-16
[9]胡永东.补肾活血汤治疗增生性骨关节病28例.陕西中医,2002,23(9):805-806
[10]李斌.自拟化骨散治疗增生性膝关节炎28例.四川中医,2002,20(7):67-68
[11]陈本华.祛痹方治疗骨关节炎35例临床观察.福建中医药,2002,33(1):13-14
[12]蔚金建,王临青.益肾除痹方治疗膝骨性关节炎114例临床观察.甘肃中医,2005,15(4):18
[13]陈广祯,李心沁.从瘀血痰湿论治膝关节骨性关节炎58例.山东中医药大学学报,1998,22(1):30
[14]严培军,孙玉明.从痰瘀水论治膝关节骨性关节炎176例.南京中医药大学学报:自然科学版,2000,16(4):249
[15]杜双庆,张青春.膝骨性关节炎中医诊治进展.云南中医药,2003,19(6):34
[16]杨久山,张维文.通痹汤治疗膝骨性关节炎伴关节积液24例.山东中医药大学学报,2000,24(6):446-447
[17]杨挺,王培民,诸方受.膝宁方治疗肾阳虚寒湿证膝骨关节炎患者的康复评定.辽宁中医杂志,2007,34(3):294
[18]周斌,樊粤光,曾意荣.中药关节康治疗膝骨性关节炎的临床研究.广州中医药大学学报,2006,23(6):476
[19]邬亚军,赵治友,何永生.中药治疗膝关节骨关节炎的临床观察.四川中医,2006,24(6):80
[20]谢国平,樊粤光.补肝肾方治疗膝关节骨性关节炎的生存质量评价.中医药导报,2005,11(9):24
[21]曹月龙,郑昱新等.养血软坚胶囊治疗膝骨关节炎疗效及安全性评价的随机对照 试验.中国药物与临床,2004,4(6):423
[22]王世彪,郁俊文等.骨痹威灵丸治疗骨性关节炎临床研究.中国中医骨伤科杂志,2004,12(3):41
[23]刘继华,张快强等.通痹丸治疗膝骨关节炎90例.陕西中医,2005,26(3):219
[24]马明明.中医辨证治疗中老年膝关节骨性关节炎98例.河北中医,2002,24(2):107
[25]吴林生,金嫣丽.中药及手法治疗膝关节骨性关节炎121例疗效分析.中医杂志,1993,34(12):742
[26]董忠.63例膝关节骨性关节炎的中医康复治疗.福建中医学院学,2000,10(2):24-25
[27]张建福,罗小鹏.骨伤疼痛疾病的中西医诊疗.北京:中医古籍出版社,2002
[28]任超西,赵明山.辨证论治退行性膝关节骨性关节病300例.河南中医学院学报,2004,19(113):58
[29]周京华,李建民.中药治疗膝关节骨性关节炎的临床观察.2004,21(2):93
[30]王少山,张世华等.骨病中西医诊断学.北京:中国中医药出版社,2002,18:6
[31]周翠英,孙素平.风湿病中西医诊疗学.北京:中国中医药出版社,1998:461
[32]宏树臣.中医指针综合治疗膝关节骨性关节炎.中国骨伤,1998,11(5):23
[33]许书亮,苏友新.骨炎汤治疗膝骨性关节炎158例临床研究.中国中医骨伤科杂志,2001.9(1)
[34]陈炳坤.当归四逆汤加减治疗膝骨性关节炎85例疗效观察.中医正骨,1995,7(5):30
[35]向开兴,肖建军.杜仲灵仙汤治疗骨性关节炎88例体会.湖南中医药导报,2004,10(11):36
[36]李正华,詹奇.补骨方治疗膝骨性关节炎的疗效观察.现代医院,2004,4(11):32-33
[37]王颢.正清风痛宁治疗骨性关节炎86例.湖南中医杂志,2000,16(5):37
[38]姚树源.痹祺胶囊治疗膝骨性关节炎的临床观察.天津中医药,2004,21(4):285
[39]王世彪,郁俊文等.骨痹威灵丸治疗骨性关节炎临床研究.中国中医骨伤科杂志,2004,12(3):41
[40]郭豪.消痛骨增停治疗膝关节骨性关节炎疗效观察.中医正骨,2004,16(9):50
[41]齐立卿,张晶.扶元荣骨汤治疗膝骨关节炎64例疗效观察.辽宁中医杂志,2005,32(10):1039-1040
[42]谢心军.加味思仙续断方治疗膝关节骨关节炎疗效观察.中医正骨,2005,17(7):13-17
[43]雷波,刘定安.从瘀血痰湿论治膝关节骨关节病48例临床观察.湖南中医杂 志,1999,15(2):12-13
[44]李志敏,周文雄.归元散方治疗膝骨性关节炎的疗效观察.海南医学,2005,16(10):159-160
[45]林岩德.活血消赘汤治疗膝关节骨关节炎42例疗效观察.河北中医,2003,25(11):819-820
[46]曾意荣,樊粤光等.补肾活血中药治疗肾虚血瘀型膝骨性关节炎的临床研究.广州中医药大学学报,2007,24(4):276-278
[47]周尊谦,谢林.丹紫康冲剂治疗膝关节退行性骨关节病的临床研究.中国骨伤.1996,9(16):12
[49]赵钟文.从补肾入手缓解膝关节骨性关节炎疼痛60例疗效观察.云南中医中药杂志,2005,26(6):10
[50]季守贤,包洪.补肾壮骨汤治疗膝关节骨性关节炎42例.四川中医,2005,23(12):82
[51]王勇,王天学.益肾宣痹汤治疗膝关节骨性关节炎.甘肃中医学院学报,2002,19(4):35
[52]黄枫,唐勇.补肾强膝方对绝经后妇女膝骨性关节炎的影响.中医正骨,2002.14(4)
[53]刘洪旺,刘志刚.退行性膝关节骨性关节病的中医辨证施治.中国骨伤,1997,10(4):27
[54]陆智.四妙散合独活寄生汤加减治疗风湿性膝关节炎104例.四川中医,1996,14(10):38
[55]杜天信,任汉阳.寒湿痹片治疗寒湿痹阻型风湿病的临床观察.中医正骨,2002,14(8):5
[56]高翔,王拥军等.益气化瘀利水方对兔膝骨关节炎组织形态学的影响.老年医学与保健,2004,10(2):81-83
[57]高文香,任汉阳等.补肾法与活血法治疗兔膝骨关节炎的病理形态学对比研究.中医正骨,2000,12(6):5-8
[58]张磊,胡阿威等.痹康灵对骨关节炎治疗作用的实验研究.中医正骨,2004,16(7):388-391
[59]王文瑞,刘宏泽,卫小春,等1 川芎嗪防治膝关节软骨退变的实验研究[J]1 中国骨伤,2004,17(2):80-82
[60]王秀华,苏姿兵.丹参注射液对兔骨关节炎软骨的影响.辽宁中医杂志,2003,30(10):860-861
[61]刘瑞波,胡廉君等.牛膝滑膜炎冲剂治疗实验性膝关节滑膜炎的组织病理学观察研究.河北中医,2000,6(4):308-311
[62]万荣,杨庆铭.黑虎丹治疗兔骨关节炎的实验研究.中国骨伤,2001,14(2):85-87
[63]周丕琪,沈霖等.补肾法治疗骨关节炎合并骨质疏松患者的作用机理研究.中国中医骨伤科杂志,2003,11(5):22-24
[64]胡阿威,张磊等.痹康灵对骨关节炎动物模型中白细胞介素-1 β水平的影响中华医学丛刊,2003,3(8):11-13
[65]潘海乐,曲波.参麦注射液对骨关节炎动物模型血液中白细胞介素1水平的影响.中国中医骨伤科杂志,2000,8(1):17-18
[66]陈飞雁,顾湘杰等.威灵仙注射液对骨关节炎关节液与软骨白介素-1水平的影响.中国矫形外科杂志,2004,12(7):524-526
[67]宁显明,樊粤光等.补肾中药对膝骨关节炎软骨TGF2 β1表达的影响.中国中医骨伤科杂志,2004,12(1):36-38
[68]潘浩,胡庆丰等.补肾壮筋汤对兔早期实验性骨关节炎软骨细胞凋亡及PCNA表达的影响.中国中医骨伤科杂志,2004,12(4):16-19
[69]沈霖,沈耀.丹参注射液对维甲酸诱导的软骨细胞凋亡的影响.中国中医骨伤科杂志,2002,10(5):1-4
[70]张梅,李萍.马钱子碱对一氧化氮诱导软骨细胞凋亡的影响.中国临床康复,2003,7(26):3554-3556
[71]肖经难,谢丹.六味地黄丸对兔骨关节炎软骨细胞凋亡的影响.湖南中医学院学报,2003,23(5):11-13
[72]杨平林,刘德玉等.补肾活血中药对膝骨性关节炎家兔血清、滑膜及关节软骨一氧化氮水平的影响.中国骨伤,2003,16(11):667-669
[73]刘世清,贺翎.七叶亭对骨关节炎的修复作用.武汉大学学报(医学版),2004,25(5):567-570
[74]唐勇,姜杰等.骨炎定对兔实验性膝骨关节炎关节软骨中iNOS表达的影响.云南中医学院学报,2004,27(1):20-22
[75]唐兴容,梁伯进等.丹菟注射液对创伤性关节炎大鼠血清氧自由基水平影响的实验研究.新中医,2002,34(6):72-73
[76]江中潮,何洪阳等.骨生注射液对实验性骨性关节炎家兔血浆SOD和MDA的影响.中国骨伤,2004,17(10):593-595
[77]马建兵,刘德玉等.中药对家兔实验性膝关节骨性关节炎氧自由基代谢的影响.中医正骨,2000,12(1):8-10
[78]黎立,张俊忠等.蠲痹合剂治疗骨性关节炎的实验研究.中医正骨,2004,16(7):391-393
[79]吴,高翔等.益气化瘀利水方对骨关节炎兔前列腺素代谢的影响.老年医学与保健,2004,10(1):24-26
[80]曹月龙,冯伟等.软骨Ⅱ号对骨关节炎兔不同部位PGE2选择性抑制作用的实验研究.中国骨伤,2001,14(10):597-598
[81]褚立希,周恩元等.关节Ⅰ号方治疗骨关节炎的实验研究.上海中医药大学学报,2001,15(1):47-50
[83]王济伟.中药对实验性骨关节炎膝旁骨内压的影响.中医正骨,1997,9(4):1
[85]万荣,杨庆铭.黑虎丹治疗兔骨关节炎的实验研究.中国骨伤,2001,14(2):85-88
[86]黄枫,唐勇.补肾强膝方对绝经后妇女膝骨性关节炎的影响.中医正骨,2002,14(4):12
[87]张宜.针刺治疗膝骨关节炎发作的临床观察.现代中西医结合杂志,2003,12(22):2406-2407
[88]黄静.瘢痕灸治疗膝骨关节炎50例疗效观察.JCAM,2002,18(3):44-45
[89]曹银香,杨少军.温针灸治疗骨性膝关节炎42例.陕西中医,2006,27(5):604
[91]张必萌,吴耀持.长针透刺治疗膝骨关节炎的临床研究.中国针灸,2004,24(9):613-614
[92]陶群,陆惠新.腹针配合局部取穴治疗膝骨关节炎疗效观察.中国针灸,2003,23(12):719-720
[93]姜忠华.温针灸为主治疗中老年骨性关节炎临床观察.中医外治杂志,2004,13(3):43
[94]薛传疆,叶明拥.推拿手法治疗膝关节骨性关节病.中国骨伤,1997,10(5)
[95]魏森苗.推拿治疗原发性膝关节骨关节炎原理探讨.按摩与导引,2002,18(2):38
[96]谢利民.张涛研究员治疗膝关节软骨退行性疾病的手法特点.中医正骨,1999,11(5):51
[97]刘克龙.手法治疗膝关节骨关节病80例.中国民间疗法,2004,12(11):22
[98]蒋生云.推拿治疗膝关节骨关节炎50例体会.按摩与导引,2003,19(1):36-37
[99]杨宏.推拿治疗膝关节增生性骨关节炎156例.中国中医药信息杂志,2001,8(11):80,83
[101]粱志强,张葆青.金桂外洗方湿热敷治疗膝关节骨性关节炎.甘肃中医学院学报,2002,19(1):20-21
[102]尹文芹.蓖麻子、鲜荠菜外用治疗骨关节疼痛.国外中医理论月刊,2005,14(2):56
[103]任永新,杜敏等.风湿痹痛膏外贴穴位治疗痹证80例.陕西中医,2003,24(12):1068-1069
[104]陈利新,马少云.中药离子导人治疗膝关节骨性关节炎400例临床报告.医学理论与实践,2003,16(5):557-558
[105]史晓林,吴连国等.伤骨科Ⅱ号对近膝关节损伤术后功能改善的影响.中国中医 骨伤科杂志,2006,14(1):17-18
[106]梁晶,王吉民等.独活寄生汤加减结合外治法治疗骨关节炎32例疗效观察.中国误诊学杂志,2005,5(16):3049-3050
[107]黄光怀.独活寄生汤加减配合针灸治疗痹证65例临床观察.中医药导报,2006,12(9):38-39
[108]何立华.独活寄生汤加减治疗痹病52例疗效观察.中国社区医师,2003,19(16):30-31
[109]范钦平.独活寄生汤加减治疗肾虚髓亏型骨痹40例.中国中医药信息杂志,2006,13(9):74
[110]陈艺.独活寄生汤加减治疗膝关节骨质增生40例小结.湖南中医杂志,1999,15(3):27
[2]贺宪,魏春山.膝骨性关节炎的病机和防治机制探讨.山东中医杂志,2005,24(2):73
[3]徐传毅,樊粤光.肾虚血瘀与膝骨性关节炎关系初探.新中医,2002,34(3):7
[4]陈龙全,郝双阶.复方竹节参片配合穴位注射治疗膝骨性关节炎82例.陕西中医,2004,25(8):716
[5]江蓉星,汪亚强.骨关节炎的中医治疗.成都中医药大学学报,2001,24(4):11-13
[6]陈赓红.新癀片与仙骨葆合用治疗中老年骨关节退行性变的临床观察.中国中西医结合杂志,2002,22(8):586
[7]林俊宏.综合治疗膝关节骨性关节炎62例.长春中医学院学报,2002,18(1):29-30
[8]朱洪民,宁显民.黄芪桂枝五物胶囊治疗膝骨节炎临床研究.福建中医药,2002,33(3):15-16
[9]胡永东.补肾活血汤治疗增生性骨关节病28例.陕西中医,2002,23(9):805-806
[10]李斌.自拟化骨散治疗增生性膝关节炎28例.四川中医,2002,20(7):67-68
[11]陈本华.祛痹方治疗骨关节炎35例临床观察.福建中医药,2002,33(1):13-14
[12]蔚金建,王临青.益肾除痹方治疗膝骨性关节炎114例临床观察.甘肃中医,2005,15(4):18
[13]陈广祯,李心沁.从瘀血痰湿论治膝关节骨性关节炎58例.山东中医药大学学报,1998,22(1):30
[14]严培军,孙玉明.从痰瘀水论治膝关节骨性关节炎176例.南京中医药大学学报:自然科学版,2000,16(4):249
[15]杜双庆,张青春.膝骨性关节炎中医诊治进展.云南中医药,2003,19(6):34
[16]杨久山,张维文.通痹汤治疗膝骨性关节炎伴关节积液24例.山东中医药大学学报,2000,24(6):446-447
[17]杨挺,王培民,诸方受.膝宁方治疗肾阳虚寒湿证膝骨关节炎患者的康复评定.辽宁中医杂志,2007,34(3):294
[18]周斌,樊粤光,曾意荣.中药关节康治疗膝骨性关节炎的临床研究.广州中医药大学学报,2006,23(6):476
[19]邬亚军,赵治友,何永生.中药治疗膝关节骨关节炎的临床观察.四川中医,2006,24(6):80
[20]谢国平,樊粤光.补肝肾方治疗膝关节骨性关节炎的生存质量评价.中医药导报,2005,11(9):24
[21]曹月龙,郑昱新等.养血软坚胶囊治疗膝骨关节炎疗效及安全性评价的随机对照 试验.中国药物与临床,2004,4(6):423
[22]王世彪,郁俊文等.骨痹威灵丸治疗骨性关节炎临床研究.中国中医骨伤科杂志,2004,12(3):41
[23]刘继华,张快强等.通痹丸治疗膝骨关节炎90例.陕西中医,2005,26(3):219
[24]马明明.中医辨证治疗中老年膝关节骨性关节炎98例.河北中医,2002,24(2):107
[25]吴林生,金嫣丽.中药及手法治疗膝关节骨性关节炎121例疗效分析.中医杂志,1993,34(12):742
[26]董忠.63例膝关节骨性关节炎的中医康复治疗.福建中医学院学,2000,10(2):24-25
[27]张建福,罗小鹏.骨伤疼痛疾病的中西医诊疗.北京:中医古籍出版社,2002
[28]任超西,赵明山.辨证论治退行性膝关节骨性关节病300例.河南中医学院学报,2004,19(113):58
[29]周京华,李建民.中药治疗膝关节骨性关节炎的临床观察.2004,21(2):93
[30]王少山,张世华等.骨病中西医诊断学.北京:中国中医药出版社,2002,18:6
[31]周翠英,孙素平.风湿病中西医诊疗学.北京:中国中医药出版社,1998:461
[32]宏树臣.中医指针综合治疗膝关节骨性关节炎.中国骨伤,1998,11(5):23
[33]许书亮,苏友新.骨炎汤治疗膝骨性关节炎158例临床研究.中国中医骨伤科杂志,2001.9(1)
[34]陈炳坤.当归四逆汤加减治疗膝骨性关节炎85例疗效观察.中医正骨,1995,7(5):30
[35]向开兴,肖建军.杜仲灵仙汤治疗骨性关节炎88例体会.湖南中医药导报,2004,10(11):36
[36]李正华,詹奇.补骨方治疗膝骨性关节炎的疗效观察.现代医院,2004,4(11):32-33
[37]王颢.正清风痛宁治疗骨性关节炎86例.湖南中医杂志,2000,16(5):37
[38]姚树源.痹祺胶囊治疗膝骨性关节炎的临床观察.天津中医药,2004,21(4):285
[39]王世彪,郁俊文等.骨痹威灵丸治疗骨性关节炎临床研究.中国中医骨伤科杂志,2004,12(3):41
[40]郭豪.消痛骨增停治疗膝关节骨性关节炎疗效观察.中医正骨,2004,16(9):50
[41]齐立卿,张晶.扶元荣骨汤治疗膝骨关节炎64例疗效观察.辽宁中医杂志,2005,32(10):1039-1040
[42]谢心军.加味思仙续断方治疗膝关节骨关节炎疗效观察.中医正骨,2005,17(7):13-17
[43]雷波,刘定安.从瘀血痰湿论治膝关节骨关节病48例临床观察.湖南中医杂 志,1999,15(2):12-13
[44]李志敏,周文雄.归元散方治疗膝骨性关节炎的疗效观察.海南医学,2005,16(10):159-160
[45]林岩德.活血消赘汤治疗膝关节骨关节炎42例疗效观察.河北中医,2003,25(11):819-820
[46]曾意荣,樊粤光等.补肾活血中药治疗肾虚血瘀型膝骨性关节炎的临床研究.广州中医药大学学报,2007,24(4):276-278
[47]周尊谦,谢林.丹紫康冲剂治疗膝关节退行性骨关节病的临床研究.中国骨伤.1996,9(16):12
[49]赵钟文.从补肾入手缓解膝关节骨性关节炎疼痛60例疗效观察.云南中医中药杂志,2005,26(6):10
[50]季守贤,包洪.补肾壮骨汤治疗膝关节骨性关节炎42例.四川中医,2005,23(12):82
[51]王勇,王天学.益肾宣痹汤治疗膝关节骨性关节炎.甘肃中医学院学报,2002,19(4):35
[52]黄枫,唐勇.补肾强膝方对绝经后妇女膝骨性关节炎的影响.中医正骨,2002.14(4)
[53]刘洪旺,刘志刚.退行性膝关节骨性关节病的中医辨证施治.中国骨伤,1997,10(4):27
[54]陆智.四妙散合独活寄生汤加减治疗风湿性膝关节炎104例.四川中医,1996,14(10):38
[55]杜天信,任汉阳.寒湿痹片治疗寒湿痹阻型风湿病的临床观察.中医正骨,2002,14(8):5
[56]高翔,王拥军等.益气化瘀利水方对兔膝骨关节炎组织形态学的影响.老年医学与保健,2004,10(2):81-83
[57]高文香,任汉阳等.补肾法与活血法治疗兔膝骨关节炎的病理形态学对比研究.中医正骨,2000,12(6):5-8
[58]张磊,胡阿威等.痹康灵对骨关节炎治疗作用的实验研究.中医正骨,2004,16(7):388-391
[59]王文瑞,刘宏泽,卫小春,等1 川芎嗪防治膝关节软骨退变的实验研究[J]1 中国骨伤,2004,17(2):80-82
[60]王秀华,苏姿兵.丹参注射液对兔骨关节炎软骨的影响.辽宁中医杂志,2003,30(10):860-861
[61]刘瑞波,胡廉君等.牛膝滑膜炎冲剂治疗实验性膝关节滑膜炎的组织病理学观察研究.河北中医,2000,6(4):308-311
[62]万荣,杨庆铭.黑虎丹治疗兔骨关节炎的实验研究.中国骨伤,2001,14(2):85-87
[63]周丕琪,沈霖等.补肾法治疗骨关节炎合并骨质疏松患者的作用机理研究.中国中医骨伤科杂志,2003,11(5):22-24
[64]胡阿威,张磊等.痹康灵对骨关节炎动物模型中白细胞介素-1 β水平的影响中华医学丛刊,2003,3(8):11-13
[65]潘海乐,曲波.参麦注射液对骨关节炎动物模型血液中白细胞介素1水平的影响.中国中医骨伤科杂志,2000,8(1):17-18
[66]陈飞雁,顾湘杰等.威灵仙注射液对骨关节炎关节液与软骨白介素-1水平的影响.中国矫形外科杂志,2004,12(7):524-526
[67]宁显明,樊粤光等.补肾中药对膝骨关节炎软骨TGF2 β1表达的影响.中国中医骨伤科杂志,2004,12(1):36-38
[68]潘浩,胡庆丰等.补肾壮筋汤对兔早期实验性骨关节炎软骨细胞凋亡及PCNA表达的影响.中国中医骨伤科杂志,2004,12(4):16-19
[69]沈霖,沈耀.丹参注射液对维甲酸诱导的软骨细胞凋亡的影响.中国中医骨伤科杂志,2002,10(5):1-4
[70]张梅,李萍.马钱子碱对一氧化氮诱导软骨细胞凋亡的影响.中国临床康复,2003,7(26):3554-3556
[71]肖经难,谢丹.六味地黄丸对兔骨关节炎软骨细胞凋亡的影响.湖南中医学院学报,2003,23(5):11-13
[72]杨平林,刘德玉等.补肾活血中药对膝骨性关节炎家兔血清、滑膜及关节软骨一氧化氮水平的影响.中国骨伤,2003,16(11):667-669
[73]刘世清,贺翎.七叶亭对骨关节炎的修复作用.武汉大学学报(医学版),2004,25(5):567-570
[74]唐勇,姜杰等.骨炎定对兔实验性膝骨关节炎关节软骨中iNOS表达的影响.云南中医学院学报,2004,27(1):20-22
[75]唐兴容,梁伯进等.丹菟注射液对创伤性关节炎大鼠血清氧自由基水平影响的实验研究.新中医,2002,34(6):72-73
[76]江中潮,何洪阳等.骨生注射液对实验性骨性关节炎家兔血浆SOD和MDA的影响.中国骨伤,2004,17(10):593-595
[77]马建兵,刘德玉等.中药对家兔实验性膝关节骨性关节炎氧自由基代谢的影响.中医正骨,2000,12(1):8-10
[78]黎立,张俊忠等.蠲痹合剂治疗骨性关节炎的实验研究.中医正骨,2004,16(7):391-393
[79]吴,高翔等.益气化瘀利水方对骨关节炎兔前列腺素代谢的影响.老年医学与保健,2004,10(1):24-26
[80]曹月龙,冯伟等.软骨Ⅱ号对骨关节炎兔不同部位PGE2选择性抑制作用的实验研究.中国骨伤,2001,14(10):597-598
[81]褚立希,周恩元等.关节Ⅰ号方治疗骨关节炎的实验研究.上海中医药大学学报,2001,15(1):47-50
[83]王济伟.中药对实验性骨关节炎膝旁骨内压的影响.中医正骨,1997,9(4):1
[85]万荣,杨庆铭.黑虎丹治疗兔骨关节炎的实验研究.中国骨伤,2001,14(2):85-88
[86]黄枫,唐勇.补肾强膝方对绝经后妇女膝骨性关节炎的影响.中医正骨,2002,14(4):12
[87]张宜.针刺治疗膝骨关节炎发作的临床观察.现代中西医结合杂志,2003,12(22):2406-2407
[88]黄静.瘢痕灸治疗膝骨关节炎50例疗效观察.JCAM,2002,18(3):44-45
[89]曹银香,杨少军.温针灸治疗骨性膝关节炎42例.陕西中医,2006,27(5):604
[91]张必萌,吴耀持.长针透刺治疗膝骨关节炎的临床研究.中国针灸,2004,24(9):613-614
[92]陶群,陆惠新.腹针配合局部取穴治疗膝骨关节炎疗效观察.中国针灸,2003,23(12):719-720
[93]姜忠华.温针灸为主治疗中老年骨性关节炎临床观察.中医外治杂志,2004,13(3):43
[94]薛传疆,叶明拥.推拿手法治疗膝关节骨性关节病.中国骨伤,1997,10(5)
[95]魏森苗.推拿治疗原发性膝关节骨关节炎原理探讨.按摩与导引,2002,18(2):38
[96]谢利民.张涛研究员治疗膝关节软骨退行性疾病的手法特点.中医正骨,1999,11(5):51
[97]刘克龙.手法治疗膝关节骨关节病80例.中国民间疗法,2004,12(11):22
[98]蒋生云.推拿治疗膝关节骨关节炎50例体会.按摩与导引,2003,19(1):36-37
[99]杨宏.推拿治疗膝关节增生性骨关节炎156例.中国中医药信息杂志,2001,8(11):80,83
[101]粱志强,张葆青.金桂外洗方湿热敷治疗膝关节骨性关节炎.甘肃中医学院学报,2002,19(1):20-21
[102]尹文芹.蓖麻子、鲜荠菜外用治疗骨关节疼痛.国外中医理论月刊,2005,14(2):56
[103]任永新,杜敏等.风湿痹痛膏外贴穴位治疗痹证80例.陕西中医,2003,24(12):1068-1069
[104]陈利新,马少云.中药离子导人治疗膝关节骨性关节炎400例临床报告.医学理论与实践,2003,16(5):557-558
[105]史晓林,吴连国等.伤骨科Ⅱ号对近膝关节损伤术后功能改善的影响.中国中医 骨伤科杂志,2006,14(1):17-18
[106]梁晶,王吉民等.独活寄生汤加减结合外治法治疗骨关节炎32例疗效观察.中国误诊学杂志,2005,5(16):3049-3050
[107]黄光怀.独活寄生汤加减配合针灸治疗痹证65例临床观察.中医药导报,2006,12(9):38-39
[108]何立华.独活寄生汤加减治疗痹病52例疗效观察.中国社区医师,2003,19(16):30-31
[109]范钦平.独活寄生汤加减治疗肾虚髓亏型骨痹40例.中国中医药信息杂志,2006,13(9):74
[110]陈艺.独活寄生汤加减治疗膝关节骨质增生40例小结.湖南中医杂志,1999,15(3):27