复元胶囊对大鼠膝骨关节炎软骨中ADAMTS-4、5的影响

目的观察复元胶囊(FYJN)对实验性大鼠膝骨关节炎软骨组织蛋白聚糖酶1、2的影响。方法 60只雄性成年SD大鼠随机分为正常组,模型组,抗骨增生胶囊组,复元胶囊低、中、高剂量组,每组10只。除正常组外,其余各组采用Hulth法建立骨关节炎动物模型。造模1 w后,各组给予相应药物灌胃,正常组和模型组给予等体积生理盐水灌胃。治疗4 w后提取各组胫骨平台软骨组织,HE染色关节软骨Mankin评分,免疫组化法和蛋白印迹法检测关节软骨中蛋白聚糖酶1、2的蛋白表达量,并采用RT-PCR法测定组织中蛋白聚糖酶1、2的mRNA表达量。结果复元胶囊组和抗骨增生胶囊组软骨Mankin's评分明显低于模型组(P<0.01),复元胶囊高剂量组软骨组织中蛋白聚糖酶1、2的表达明显低于抗骨增生胶囊组(P<0.05)。结论复元胶囊显著降低大鼠膝关节软骨中ADAMTS-4和ADAMTS-5的表达,提示复元胶囊可能通过抑制蛋白聚糖酶,减少蛋白多糖的降解达到对早期骨关节炎防治作用。     

复元胶囊对膝骨关节炎模型血清软骨寡聚基质蛋白的影响

目的 观察复元胶囊对实验性膝骨关节炎(OA)模型病理形态及血清中软骨寡聚基质蛋白(COMP)的影响.方法 72只雄性SD大鼠随机分成正常组、模型组、壮骨关节丸组、复元胶囊组,每组18只.除正常组外,其余各组采用Hulth法建立膝OA动物模型.造模后,壮骨关节丸组、复元胶囊组分别给予壮骨关节丸、复元胶囊灌胃,而正常组、模型组给予生理盐水.灌胃后4、8、12 w分别随机选取6只进行X线摄片取材.通过X线摄片、肉眼观察、Mankin评分以及电镜检测评价复元胶囊治疗OA疗效,酶联免疫吸附法检测血清中COMP水平.结果 复元胶囊组膝关节x线积分、Mankin评分在4、8、12 w三个时间点均显著低于模型组(P<0.01),复元胶囊组血清COMP水平也低于模型组(P<0.01).结论 复元胶囊能降低血清软骨代谢标志物COMP水平,延缓OA软骨退变过程.     

复元胶囊对大鼠膝骨关节炎模型软骨细胞凋亡及增殖的影响

目的观察复元胶囊对实验性大鼠膝骨关节炎(OA)模型软骨细胞凋亡及细胞核增殖抗原(PCNA)mRNA表达的影响,探讨其治疗骨关节炎的作用机制。方法 48只雄性SD大鼠随机分成正常组、模型组、壮骨关节丸组、复元胶囊组,每组12只。除正常组外,其余各组采用Hulth法建立膝OA动物模型。4 w后,壮骨关节丸组、复元胶囊组分别给与壮骨关节丸、复元胶囊灌胃,而正常组、模型组给予生理盐水。8 w后,通过肉眼观察、Mankin's评分评价复元胶囊治疗OA疗效,透射电镜、原位末端标记法(TUNEL法)检测软骨细胞凋亡,硝酸还原酶法测定关节液中一氧化氮(NO)水平,RT-PCR法检测PCNA mRNA的表达。结果复元胶囊Mankin评分、软骨细胞凋亡指数及关节液中NO水平均低于模型组(P<0.05),而PCNA mRNA的表达高于模型组(P<0.01)。结论复元胶囊能抑制OA软骨细胞的凋亡,促进软骨细胞PCNA的表达,延缓OA软骨退变过程。     

复元胶囊对膝骨关节炎模型Ⅱ型胶原羧基端肽、基质金属蛋白酶-13的影响

目的 观察复元胶囊对实验性大鼠膝骨关节炎(KOA)模型病理形态、血清Ⅱ型胶原羧基端肽(CTX-Ⅱ)及基质金属蛋白酶-13( MMP-13)的影响.方法 72只雄性老年SD大鼠随机分成正常组、模型组、抗骨增生胶囊组、复元胶囊组(高、中、低剂量组),每组12只.除正常组外,其余各组采用Hulth法建立OA动物模型.造模2w后,各实验组给予相应的药物灌胃,正常组、模型组给予等量生理盐水.灌胃后4、8、12 w分别随机选取各组4只处死,比较各组关节软骨病理变化;免疫组化法比较MMP-13水平变化;酶联免疫吸附法(ELISA)比较CTX-Ⅱ水平变化.结果 实验组Mankin评分明显低于模型组(P＜0.01);复元胶囊中、高剂量组MMP-13及CTX-Ⅱ较模型组表达明显下调,差异有统计学意义(P＜0.05).结论 复元胶囊能够抑制关节软骨MMP-13及降解产物CTX-Ⅱ的表达,对防治关节软骨退变有一定的积极意义.     

复元胶囊对大鼠膝骨关节炎软骨iNOS及血清PGE2、NO的影响

目的 观察复元胶囊(FYJN)对实验性大鼠膝骨关节炎软骨诱导型一氧化氮合酶(iNOS)及血清一氧化氮(NO)、前列腺素E2(PGE2)的影响.方法 Hulth法建立骨关节炎模型,随机分成正常组、模型组、塞来昔布(CE)组、FYJN低、中、高剂量组,各组分别予相应药物灌胃12 w.HE染色并光镜观察股骨内侧髁软骨病理形态,免疫组化检测软骨中iNOS表达,硝酸基还原酶法及酶联免疫吸附法分别测定血清NO、PGE2含量.结果 FYJN低、中、高剂量组软骨iNOS及血清NO、PGE2均低于模型组(P<0.05,P<0.01,P<0.001).结论 FYJN呈剂量依赖关系降低骨关节炎软骨中iNOS表达及血清中NO、PGE2含量,对减轻关节炎症有一定的作用.     

复元胶囊对膝骨关节炎大鼠IL-1β、OPG和OPGL mRNA表达的影响

目的观察复元胶囊对膝骨关节炎(OA)大鼠关节软骨中白细胞介素(IL)1β、骨保护素(OPG)及其配体(OPGL)的影响。方法 60只雄性SD大鼠随机分为6组:①正常组10只,不给予任何处理;②模型组10只,Hulth法造模后用生理盐水10 ml/d灌胃;③抗骨增生胶囊组10只,Hulth法造模后每日给予抗骨增生胶囊灌胃;④复元胶囊高、中、低组各10只,Hulth法造模后用不同浓度复元胶囊灌胃。于给药第12周处死大鼠,取各组大鼠膝关节内踝关节软骨标本,观察大体结构并分级;HE染色,观察其镜下结构;反转录-多聚酶链式反应(RT-PCR)法检测膝关节软骨中IL-1β、OPG及OPGL mRNA的表达含量。结果动物模型造模成功,HE染色评分中,复元胶囊高、中剂量组及抗骨增生胶囊组软骨退变程度较模型组明显减轻(P<0.01),复元胶囊组高剂量组OPG mRNA的表达量显著高于模型组(P<0.01),IL-1βmRNA及OPGL mRNA的表达显著低于模型组(P<0.05),OPG与OPGL比率显著高于模型组(P<0.01)和正常组(P<0.01)。结论复元胶囊能够上调软骨中OPG mRNA的表达,下调IL-1βmRNA及OPGL mRNA的表达,使OPG与OPGL的比率上升,表明对软骨退变及软骨下骨的破坏有一定的预防作用。     

复元胶囊对衰老性骨关节炎模型兔血清氧自由基代谢及血液流变学的影响

目的观察复元胶囊对衰老性骨关节炎模型兔血清总超氧化酶歧化物(T-SOD)、丙二醛(MDA)以及血液流变的影响。方法 52只健康新西兰大白兔随机分为正常组、模型对照组、模型组、奥泰灵组、复元胶囊低剂量组、复元胶囊中剂量组及复元胶囊高剂量组。模型对照组右后肢伸直石膏固定,模型组在模型对照组基础上颈背部皮下注射D半-乳糖。各药物组用灌胃方式给药6 w。酶标仪检测血清T-SOD和MDA光密度,计算T-SOD活力和MDA浓度。全自动血液流变分析仪测全血黏度。结果造模6 w后,模型组与模型对照组关节软骨出现典型骨关节炎病理改变。模型组血清T-SOD活力降低和MDA浓度升高,与正常组和模型对照组比较差异均有统计学意义(P0.05),与正常组比较,血黏度指标不同程度升高,差异有统计学意义(P0.05)。用药6 w后,复元胶囊各组与模型组比较,软骨病理改变减轻,T-SOD活力增强,MDA浓度降低,差异有统计学意义(P0.05);血黏度指标变化,差异无统计学意义(P0.05)。复元胶囊高剂量组与低、中剂量比较,T-SOD和MDA变化差异有统计学意义(P0.05)。结论复元胶囊不能改善模型兔血液黏度,但能够抑制氧自由基过度生成,起到延缓衰老,保护软骨的作用。     

金天格胶囊对膝骨关节炎患者关节软骨及膝关节功能的作用及机制

目的探讨金天格胶囊治疗膝骨关节炎(KOA)患者的疗效及对关节软骨及膝关节功能的作用机制。方法 KOA患者60例,按随机数字表法分为观察组及对照组各30例,对照组予依托考昔片治疗,1次/d,1片/次,4 w为1个疗程。观察组予金天格胶囊治疗,3次/d,3粒/次,4 w为1个疗程。两组患者均治疗3个疗程。评价两组患者疗效及膝关节功能情况,比较两组患者治疗前、治疗12 w后白细胞介素(IL)-1β、转化生长因子(TGF)-β1、基质金属蛋白酶组织抑制剂(TIMP)-1及基质金属蛋白酶(MMP)-3水平。统计两组患者不良反应情况。结果两组总有效率比较差异无统计学意义(P>0.05)。治疗前两组患者西安大略和麦克马斯特大学骨关节炎调查量表(WOMAC)评分比较差异无统计学意义(P>0.05),治疗后观察组WOMAC评分中疼痛、僵硬、日常生活、综合评分均低于对照组(P<0.05)。治疗后观察组IL-1β、MMP-3水平均低于对照组,TGF-β1、TIMP-1高于对照组(P<0.05);观察组不良反应率低于对照组(P<0.05)。结论采用金天格胶囊治疗KOA患者疗效显著,可明显改善患者膝关节功能,安全性高,可通过促进TIMP-1、TGF-β1的表达和抑制MMP-3、IL-1β的表达,从而达到抗炎的效果。     

复元胶囊对实验性骨关节炎软骨中MMP13、TIMP1及TIMP2的影响

目的观察复元胶囊对实验性骨关节炎软骨中基质金属蛋白酶13、组织型金属蛋白酶抑制剂1,2及病理形态方面的影响。方法选用新西兰兔66只,随机分为:正常对照组6只,不给予任何处理;模型对照组12只,造模后生理盐水灌胃;四环素组、复元胶囊低、中、高剂量组各12只,造模后分别用四环素、复元胶囊灌胃。连续灌胃4~12w后,比较各组关节软骨病理变化;免疫组化法检测兔膝关节软骨中MMP13、TIMP2蛋白质水平的变化;RT-PCR法检测关节软骨中MMP13、TIMP1及TIMP2mRNA表达。结果实验组软骨Mankin′s评分都显著低于模型对照组,实验组MMP13的mRNA表达水平明显低于模型对照组,而其TIMP1、TIMP2的mRNA的水平较模型对照组有所增加。MMP13主要表达于软骨表层及中上层,实验组MMP13表达量低于模型对照组(P<0.05)。结论复元胶囊能明显抑制骨关节炎软骨中MMP13的蛋白和mRNA的水平,能提高OA软骨中TIMP1,2的蛋白和mRNA的水平,稳定二者水平,对软骨退变有一定的防治作用。     

壮骨关节胶囊配合透明质酸钠注射液治疗老年膝骨关节炎的疗效

目的探讨壮骨关节胶囊配合透明质酸钠注射液治疗膝骨关节炎的临床疗效。方法选取2011年6月至2014年6月在该院就诊的膝骨关节炎患者48例,随机分为两组各24例。对照组:尼美舒利口服治疗,腔内注射透明质酸钠。观察组:采用尼美舒利、壮骨关节胶囊及腔内注射透明质酸钠注射液治疗。比较两组患者的临床疗效、膝部功能评分及膝部评分的变化情况。结果观察组总有效率高于对照组(P0.05)。治疗后,观察组患者膝部行走、上下阶梯、手杖支撑都高于对照组(P0.05或P0.01)。治疗后,观察组患者膝部疼痛、伸直迟滞都高于对照组(P0.05)。治疗后,观察组总评分高于对照组总评分(P0.05)。结论壮骨关节胶囊配合透明质酸钠注射液治疗膝骨关节炎疗效显著,能够改善患者膝部功能,缓解临床症状。     

芪防膝痹方治疗老年性膝骨关节病的疗效研究

目的 观察芪防膝痹方治疗膝骨关节病的临床疗效.方法 将96例患者按随机原则分为治疗组48例、对照组48例.治疗组BID口服芪防膝痹方水煎剂150 mL,对照组QD口服塞来昔布胶囊200 mg.治疗4w后,分别以Lequesne M的膝骨关节病临床评估指数打分表对治疗前后病情严重程度打分,并进行统计分析.结果 治疗组和对照组在疗效上差异无统计学意义（P＞0.05）,治疗组LequesneM表中的各项目评分与对照组差异无统计学意义（P＞0.05）.芪防膝痹方对气滞血瘀型、肝肾不足型的疗效优于风寒湿型[（89.40±9.23）vs （80.20±13.62）,P＜0.05];[（88.70±6.26）vs （80.20±13.62）,P＜0.05],对临床中期患者的效果优于早、晚期[（92.57±2.59） vs （84.63±8.01）,P＜0.05];[（92.57±2.59）vs （83.00±13.51）,P＜0.05],对X线Ⅱ期患者的效果优于Ⅰ、Ⅲ期[（92.75±2.49）vs（84.63±8.01）,P＜0.05];[（92.75±2.49）vs （81.63±13.73）,P＜0.05].结论 芪防膝痹方在临床疗效上与塞来昔布相当,在某些期或某些功能的改善上优于塞来昔布,适合临床推广.     

Balneotherapy and tap water therapy in the treatment of knee osteoarthritis

To investigate if spa water is superior to tap water (TW) in relieving the symptoms of pain, joint motion, life quality in knee osteoarthritis (KOA) patients. In this randomized placebo-controlled trial, 52 patients with KOA were followed in two groups. In group I (n = 27), patients were treated in the pool full of spa water at 37°C for 20 min a day, 5 days a week, for a period of 2 weeks. In group II (n = 25), the same protocol was used but spa water was replaced by TW heated to 37°C. Patients in both groups were given a home-based standardized exercise program. Evaluation parameters were pain (pVAS), tenderness score (TS), 50-ft walking duration, quadriceps muscle strength (QMS), active flexion degree (AFD), WOMAC OA index, and Nottingham Health Profile (NHP). The first evaluation was done after the informed consent was obtained. Second and third evaluations were done at the 2nd and 12th week. PVAS, 50-ft walking duration, AFD, TS, WOMAC, and NHP variables improved in group I. Same variables except QMS improved also in group II. Comparison of the groups just after treatment showed that only pVAS (P = 0.015), NHP pain score (P = 0.020), and TS (P = 0.002) differed significantly in favor of group I at the 2nd or 12th week. Both of the thermal treatment modalities were found to be effective in the management of the clinical symptoms and quality of life in KOA patients. However, pain and tenderness improved statistically better with balneotherapy. There were no significant differences between the groups for the other variables.     

A prospective randomised controlled clinical trial comparing the efficacy of different molecular weight hyaluronan solutions in the treatment of knee osteoarthritis

Viscosupplementation consists of injecting exagenous hyaluronan (HA) into the synovial joints to restore the normal rheological environment which deteriorates severely in osteoarthritic (OA) joints. Efficacy might be related to the rheological properties and molecular weight (MW) of the hyaluronan preparations. This prospective, controlled, double-blind, randomised clinical trial was aimed at comparing the elastoviscous properties of a high molecular weight viscosupplement, hylan G-F 20, with that of a lower molecular weight hyaluronan product in order to determine the relationship of elastoviscosity to efficacy, alongside placebo, in the treatment of patients with knee OA. The results were analysed as a completers analysis with 59 patients. Primary outcome measures included the Western Ontario and Mc Master Universities Osteoarthritis Index (WOMAC) for pain, stiffness and function scores, and patient and physician global assessments (0–100 scale). For patient (PGA) and physician global assessments (PhGA), the 0–100 scale was used, with 100 being the worst. Follow-up assessments were made at intervals of 1, 3 and 6 months after the first injection. Local adverse events, such as transient pain at the injection site or warm knee lasting for one night, were recorded in two patients (3%). In all groups, the WOMAC pain score exhibited a significant difference from the baseline value; neither treatment group was significantly different from the placebo group, but total pain score was significantly better than baseline for both of the HA groups at the end of 6 months (p < 0.05). Improvement in WOMAC physical function score favoured both sodium hyaluronate and hylan G-F 20 after the first month, and remained significant until the end of 6 months (p < 0.01). In the placebo group, the physical function scores became worse after the end of the 1st month; the scores at the end of 6 months were no different from those at the beginning. The WOMAC stiffness scores of both of the hyaluronic acid groups improved with the first injection, and remained significantly better than the placebo group until the end of the survey (p < 0.001). All groups expressed improvement with PGA scores after the first injection. At the end of 6 months all three groups were similar, but the treatment groups were significantly better than the placebo group (p < 0.05), and all were significantly better than at the beginning (p < 0.05). The PhGA scores were similar in all groups until after the third injection. The second group was slightly better in the controls at 1 and 3 months, but all the groups were similar at the end of 6 months. Although the placebo group seemed worse, it was not statistically significant. Compared with lower molecular weight HA, the higher molecular weight HA might be more efficacious in treating knee OA, but heterogeneity of previous studies limited definitive conclusions. Patients treated by injection of either of two hyaluronan preparations showed clinical improvement for pain, though no different from the placebo group; WOMAC stiffness scores were better than placebo in the HA groups, whereas PGA scores showed improvement in all groups but HA groups were better than placebo. PhGA scores were worse in the placebo group, but not to a statistically-significant extent. The HA groups did not differ in terms of clinical efficacy.     

Osteoarthritis knee hip quality of life questionnaire assessment in Egyptian primary knee osteoarthritis patients: Relation to clinical and radiographic parameters

Aim of the work: To evaluate health-related quality of life (HRQoL) in primary knee osteoarthritis (KOA) patients using the osteoarthritis knee hip quality of life (OAKHQoL) questionnaire and study its relation to clinical and radiographic parameters. Patients and methods: One hundred patients with primary KOA were studied. Knee radiography was evaluated using Kellgren Lawrence (K-L) score and the OAKHQoL questionnaire assessed. Results: The patients were 75 females and 25 males; F:M 3:1. Their mean age was 54.6?±?10.4?years, disease duration 4.6?±?2.7?years and body mass index (BMI) 28.6?±?2.7. 17 patients were hypertensive and 26 diabetics. 84 patients presented with bilateral KOA disease, joint stiffness in 43%, knee deformities in 18% and K-L score grade 3 in 56%. Pain component was found to have the least normalized OAKHQoL questionnaire score (49.8?±?15.4), while mental health domain scored the highest (60.1?±?8.2). Female gender, older age, obesity, hypertension, diabetes, bilateral KOA disease and K-L grade 3 were associated with lower questionnaire domains. Regression analysis revealed that disease duration and bilateral disease were predictors for lower scores of all OAKHQoL domains, while knee joint stiffness for four domain. Hypertension, knee deformity and K-L classification were good predictors for lower scores of two subscales. Conclusion: Egyptian patients with primary KOA have relatively poor HRQoL; reflected mainly by pain component of the OAKHQoL questionnaire. Disease duration and bilaterality were predictors for lower scores of all questionnaire domains, knee stiffness for four subscales. Hypertension, knee deformity and K-L classification were good predictors for lower scores of two subscales.     

Randomised controlled trial of extraarticular gold bead implantation for treatment of knee osteoarthritis: a pilot study

The primary objective of this double-blind, randomised, controlled trial was to determine if implanting gold beads at five acupuncture points around the knee joint improves 1-year outcomes for patients with osteoarthritis (OA) of the knee. Participants were 43 adults aged 18–80 years with pain and stiffness from non-specific OA of the knee for over a year. The intervention was blinded implantation of gold beads at five acupuncture points around the affected knee through a hypodermic needle, or needle insertion alone. Primary outcome measures were knee pain, stiffness and function assessed by the patient at 0, 1, 3, 6, 9 and 12 months and knee score and knee function assessed by an orthopaedic surgeon at 0, 6 and 12 months. Within the first month, three patients dropped out. The remaining 21/19 patients in the intervention/control groups generally improved, but there was no statistically significant difference between the groups. The improvement was shown in the patients’ self-assessment scores that decreased from randomisation until 1 year later (intervention/control group, medians): pain −1.92/−2.18 (P = 0.95, F test, general linear mixed model); stiffness −0.93/−0.43 (P = 0.11); function −7.23/−3.36 (P = 0.63). The surgeon’s scores also generally improved, i.e. increased: knee score +16.4/+8.2 (P = 0.65); knee function +10.5/+5.8 (P = 0.79). In the protocol-based subgroup analysis, the 15 intervention patients of the 32 patients who had a positive response to the initial conventional acupuncture had greater relative improvements in self-assessed outcomes. The treatment was well tolerated. This 1-year pilot study indicates that extraarticular gold bead implantation is a promising treatment modality for patients with OA of the knee. The new treatment should be tested in a larger trial including only patients who respond positively to initial conventional acupuncture. Trial registration: ClinTrials.gov ID NCT00487370     

Predictors of self-reported knee osteoarthritis in community-dwelling older women in Japan: A cross-sectional and longitudinal cohort study

PurposeThis study aimed to determine the predictors of knee osteoarthritis in community-dwelling elderly Japanese women.MethodsIn this prospective cohort study, The Tokyo Metropolitan Institute of Gerontology collected baseline data in 2008 and follow-up data in 2012 for participants from the Itabashi Ward of Tokyo, Japan. Participants were asked at each time point if they had been diagnosed with knee osteoarthritis. The baseline evaluation was conducted with 1289 community-dwelling women aged 75–85 years, of which 992 reported no history of knee osteoarthritis. The follow-up survey targeted these 992 participants; we obtained history of knee osteoarthritis from 867 of these participants. The baseline evaluation also included collection of anthropometric, fitness, hematologic, and lifestyle data.ResultsWe performed logistic regression analysis of the cross-sectional data at baseline. Participants who reported fewer light exercise sessions (≤2–4 days/week) had lower odds ratios for history of self-reported knee osteoarthritis than those who reported more frequent exercise (≥5–6 days/week). Logistic regression analysis of the longitudinal data revealed that slow walking speed ( < 65.22 m/min), low serum albumin levels ( < 4.10 g/dL), and low frequency of soy product consumption (≤1 time per 2 days) at baseline resulted in higher odds ratios for incidence of self-reported knee osteoarthritis during the 4-year follow-up period.ConclusionsThe results suggest that slow walking speed, low serum albumin, and insufficient consumption of soy products are predictors for knee osteoarthritis in elderly Japanese women. These results could help in the design of knee osteoarthritis prevention programs for elderly women.     

Effect of weight losing on the clinical status improvement of patients with knee osteoarthritis

Objective

Osteoarthritis causes severe pain and disability in joints, one of the most prevalent involved joints is the knee joint. There are several therapeutics ways to control pain and disability, but almost none of them are definite treatment. In this article, we tried to reveal the effect of weight loss on improving symptoms of knee osteoarthritis as an effective and permanent therapeutic approach.

Efficacy of intra-articular sodium hyaluronate in the treatment of knee osteoarthritis

 To assess the efficacy of intra-articular hyaluronic acid in patients with knee osteoarthritis, sixty female patients with knee osteoarthritis were randomised to three weekly intra-articular injections of 30 mg sodium hyaluronate (Na HA) with a high molecular weight (1.0 to 2.9 million Da) or 40 mg 6-methylprednisolone acetate (6-MPA). The clinical assessments included pain at rest, at weight-bearing and on walking, Lequesne Index and active range of knee flexion. Assessments were done at baseline, at week 4, and at months 3 and 6. A significant decrease in VAS scores for pain at rest, at weight-bearing and pain on walking, and in Lequesne index was found in both groups at week 4 when compared to baseline and there was no significant differences between the two groups. However, at 3^rd month improvement in all pain scores and Lequesne index was found in favour of hyaluronic acid. At 6^th, no significant difference was found between the treatment groups. Improvement in pain was accompanied by an increase in joint flexion at week 4 and at month 3 in both groups. Both treatments were well-tolerated. The results showed that both intra-articular hyaluronic acid and 6-MPA treatments provide clinically significant improvement and demonstrated that Na HA has a long-term beneficial effect in patients with knee osteoarthritis. Received: 13 May 2002 / Accepted: 21 November 2002