关节内注射医用臭氧对大鼠膝退行性关节炎的影响

[目的]观察医用臭氧膝关节腔内注射对大鼠退行性关节炎的影响，探讨不同浓度医用臭氧对退行性关节炎的防治效应及可能机理。[方法]将SD大鼠40只随机分为A（正常对照组）、B（模型组）、C（空气组）、D（35μg／ml医用臭氧组）、E（70μg／ml医用臭氧组）5组，后4组复制出膝退行性关节炎（OA）模型，D、E组依据浓度不同，隔日1次给予膝关节腔内注射医用臭氧，每次1ml，间隔一周再注射，共2周。4周后处死动物，HE染色观察光镜下关节软骨的一般形态、Masson染色进行软骨Mankin’s评分，关节灌洗液超氧化物岐化酶（SOD）、丙二醛（MDA）作为检测指标。[结果]B组光镜下关节软骨退变明显，Masson染色可见蓝绿色丢失较重，SOD下降，MDA升高；D组显微镜下关节软骨形态观察有明显改善，Mankin’s评分较A组无显著性差异，与B、C组比较有显著性差异（P〈0．05），SOD升高，MDA下降；E组显微镜下及Mankin’s评分较B组无明显改善，SOD下降，MDA升高。[结论]浓度为35μg／ml医用臭氧组能够减轻退行性关节炎软骨退变，增强机体清除自由基的能力，从而有效防治退行性关节炎，而浓度为70μg／ml医用臭氧组引起组织细胞脂质过氧化反应，导致关节软骨组织结构破坏。     

医用臭氧对膝骨关节炎兔软骨基质金属蛋白酶-1的影响

目的 探讨医用臭氧对膝骨关节炎兔软骨基质金属蛋白酶-1(MMP-1)的影响.方法 新西兰大白兔30只,体重2.2～2.8 kg,雌雄不拘,并以左膝关节作为对比,随机分为3组,每组10只,建立右膝骨关节炎(OA)模型,分别于造模成功后第3天和第5天向右膝关节腔内注入空气(A组)、40μg/L(B组)和80 μg/L(C组)医用臭氧3 ml.造模成功后第7天处死动物,取两膝关节,光镜下观察关节软骨一般形态,甲苯胺蓝染色行Mankin评分;免疫组化法检测软骨基质金属蛋白酶-1(MMP-1)的表达水平;分别于造模成功时和处死前即刻测定兔两膝关节活动度.结果 与左膝关节比较,各组造模成功时右膝关节活动度降低,软骨组织Mankin评分、软骨细胞MMP-1表达升高(P＜0.05);B组和C组处死前即刻右膝关节活动度较造模成功时升高(P＜0.05).与A组比较,B组软骨组织Mankin评分、软骨细胞MMp-1表达降低(P＜0.05);与B组比较,C组上述指标升高(P＜0.05).A组和C组软骨明显退变,程度重于B组.结论 关节腔内注射40 μg/L医用臭氧3ml治疗兔膝骨关节炎的机制可能与下调软骨MMP-1有关.     

不同浓度医用臭氧联合玻璃酸钠治疗骨性膝关节炎的临床研究

目的研究医用臭氧联合玻璃酸钠治疗骨性膝关节炎(KOA)的治疗用量。方法骨性膝关节炎患者48例,共80膝,随机分为四组,每组20膝。分别给予臭氧(A组20μg/ml、B组30μg/ml、C组40μg/ml)15 ml,每周1次,连续3周和玻璃酸钠行患膝关节腔内注射2 ml,每周一次,连续3周,对照组(D组)行玻璃酸钠膝关节腔内注射,每次2 ml,每周一次,连续5周。观察A、B、C三组治疗前后患者VAS评分、关节活动度(ROM)、Lysholm关节功能评分变化情况。结果臭氧治疗后第1周C组VAS评分低于A、B组(P<0.05);臭氧治疗后第3周C组Lysholm关节功能评分优于A、B组(P<0.05);治疗后C组患者关节肿胀、疼痛和跛行评分高于D组(P<0.05);总优良率C组高于D组(P<0.05)。结论 40μg/ml的臭氧联合玻璃酸钠可以缓解骨性膝关节炎疼痛,改善关节功能。     

医用臭氧与透明质酸钠治疗兔膝骨性关节炎的疗效比较

目的通过建立兔膝骨性关节炎动物模型,探讨医用臭氧（O3）治疗膝骨性关节炎的可行性。方法将18只家兔用伸直位固定左后肢膝关节制成兔膝骨性关节炎模型。造模成功后测量各只兔膝关节活动度,并做磁共振检查。之后将家兔随机分为3组（n=6）：对照组（骨性关节炎组）,透明质酸钠组（SH组）,臭氧（O3）组。O3组向左膝关节腔内注入10ml 35μg／ml的O3-O2混合气体;SH组向左膝关节腔内注射1％浓度的SH1ml,1次／周;对照组动物不做特殊处理。5周后再次做双膝关节活动度检查和MR检查,处死动物取膝关节股骨髁部位的关节软骨做病理切片,HE染色观察关节软骨的一般形态、番红O染色行Mankin’s评分。结果关节活动度检查、磁共振检查与病理检查均显示解除制动后骨性关节炎继续发展,关节腔内注射O3或透明质酸钠均可延缓关节炎的发展,两种治疗方法疗效差异无统计学意义。结论医用O3可减轻炎症,延缓软骨退化,改善关节活动功能,对骨性关节炎有治疗作用。     

唑来膦酸对兔膝骨关节炎模型软骨退变的保护作用

[目的]观察唑来膦酸(zoledronic acid,ZOL)干预骨关节炎(osteoarthritis,OA)软骨下骨改变及关节软骨退变的效果,探讨ZOL抑制早期OA病情进展的可能机制,为ZOL干预早期OA的疗效评价提供动物实验依据。[方法]32只新西兰兔随机分为四组:唑来膦酸高剂量组(A组)、唑来膦酸中剂量组(B组)、唑来膦酸低剂量组(C组)、安慰剂组(D组),每组8只。A、B、C组造模术后分别于耳缘静脉推注ZOL 250 ug/kg、50 ug/kg、10 ug/kg,D组推注生理盐水2 ml。造模后0、4、8周行DXA扫描,8周行MRI扫描后处死实验动物,取双侧膝关节制作病理组织学切片,比较各组膝关节影像学表现、大体形态及病理变化,并采用Mankin评分进行定量分析。[结果]造模后0、4、8周实验侧膝关节骨密度降低程度A组B组C组D组。MRI显示实验侧股骨内外髁关节软骨厚度变薄,厚度A组B组C组D组。大体标本及组织切片观察A组OA程度最轻,B、C组较重,D组最重。右膝关节Mankin评分A、B、C、D组分别为(3.67±0.82)、(4.83±1.17)、(6.33±1.21)及(7.50±1.52)。[结论]ZOL静脉注射能够增加软骨下骨骨量,改善微观结构,减轻兔膝关节不稳定诱发的OA关节软骨退变。干预效果与剂量相关,250 ug/kg、50 ug/kg组手术侧骨关节炎病变程度均较轻。     

臭氧与玻璃酸钠治疗膝骨性关节炎疗效的比较

目的比较臭氧、玻璃酸钠以及二者联合治疗膝关节骨性关节炎的临床疗效。方法膝关节骨性关节炎143例按随机数字表分为A组（48例）、B组（48例）和C组（47例）,分别以玻璃酸钠20mg、30μg/ml浓度的医用臭氧30ml和同剂量臭氧＋同剂量玻璃酸钠作患膝关节腔注射,每周1次,5次为一疗程。比较治疗前与治疗后3d、30d、60d、90d膝关节VAS疼痛评分和膝关节功能Lysaholm评分。治疗后90d,比较膝关节Leguesne评分有效率。结果VAS评分：A组治疗后30、60、90d较术前明显改善,B、C组治疗后3、30、60、90d均较术前明显改善;B组治疗后3、30d改善程度较A组大,差异有统计学意义（P〈0．05）,但治疗后60、90d2组差异无统计学意义（P〉0．05）;C组治疗后3、30、60、90d均较A、B组改善明显,差异有统计学意义（P〈0．05）。膝关节功能Lysholm评分：A、C组治疗后30、60、90d均较治疗前明显提高,差异有统计学意义（P〈0．05）;而B组治疗后30、60d均较治疗前明显提高,但治疗后90d时与治疗前比较差异无统计学意义（P〉0．05）;A组治疗后90d明显高于B组,差异有统计学意义（P〈0．05）;C组治疗后30、60、90d均明显高于A、B组,差异有统计学意义（P〈0．05）。A、B组Leguesne疗效评分有效率差异无统计学意义（P〉0．05）,C组Leguesne疗效评分有效率明显较A、B组高。差异有统计学意义（P〈0．05）。结论应用臭氧治疗膝关节骨性关节炎能减轻关节疼痛,改善膝关节功能;而单用玻璃酸钠则疗效起效慢,但较单用臭氧稳定;二者联用不仅起效快、效果好,而且疗效稳定。     

臭氧液对兔膝骨性关节炎滑膜炎症的影响

目的评价臭氧液对兔膝骨性关节炎滑膜炎症的影响。方法新西兰兔32只,采用随机数字表法分为四组,每组8只。A组不予任何处理;B组仅造模;C组造模成功后,关节腔注射20μg/ml臭氧液2ml,每周1次,连续3周;D组不造模,仅行关节腔注射臭氧液,方法同C组。观察膝关节滑膜形态,检测滑膜组织中IL-6和TNF-α含量。结果 A组滑膜组织无充血水肿,滑膜细胞无增生现象,滑膜组织结构正常;B组滑膜组织正常结构破坏,细胞重度增生,炎性细胞浸润明显,血管增生充血,滑膜厚度较A组明显增加;C组滑膜组织炎症细胞减少,充血水肿减轻,滑膜厚度较B组明显降低;D组滑膜无炎症表现。与A组比较,D组IL-6和TNF-α含量无明显增高,B、C组IL-6和TNF-α含量明显增高(P0.05),但C组明显低于B组(P0.05)。结论关节腔注射20μg/ml臭氧液2ml可以减轻滑膜炎症,降低滑膜中IL-6和TNF-α含量,且对正常关节滑膜组织无明显损害。     

肺表面活性物质对胎粪吸入鼠肺功能的影响

目的：探讨外源性肺表面活性物质（PS）对胎粪吸入鼠肺功能的影响。方法：28只Wistar大白鼠进行人工通气，经气道注入3－4ml/kg胎粪溶液，PaO2降至20kPa以下后将动物随机分为4组（每组7只）。A组，气道内注入PS 150mg/kg(50mg/ml,3ml/kg)；B组，气道内注入等量生理盐水；C组，用PS稀溶液75mg/kg(5mg/ml,15ml/kg)进行支气管肺泡灌洗，重复2次；D组，用15ml/kg的生理盐水灌洗双肺。治疗后15min,30min,60min,120min,180min采血进行血气分析。180min后测定各组潮气量，并进行支气管肺泡灌洗（BAL），检测BAL液中总蛋白（TP）和TNF－α含量。结果：治疗后A和C组PaO2均明显升高，而B和D组在治疗后几乎不变，A、C组与B、D组相比，P＜0．05。A与C组间差异均无显著性。A和C组的潮气量明显高于B和D组（P＜0．05）。A和C组的BAL液中TP含量明显低于B和D组（P＜0．05）。TNF－α含量各组间无差异。结论：补充PS明显改善胎粪吸入鼠肺的氧合和顺应性。PS稀溶液灌洗法优于气道注入法。     

血必净联合维拉帕米对大鼠小肠缺血再灌注损伤的实验研究

目的探讨血必净联合维拉帕米对大鼠小肠缺血再灌注（I／R）损伤的保护作用及其可能机制。方法制作小肠缺血再灌注模型,SD大鼠50只随机分为假手术组（A组）、缺血再灌注组（B组）、血必净组（c组）、维拉帕米组（D组）及血必净和维拉帕米联合治疗组（E组）,各10只。分别检测各组大鼠小肠缺血45min再灌注0h、2h时血清中肿瘤坏死因子α（TNF—α）、白细胞介素1β（IL-1β）、丙二醛（MDA）的含量;同时观察小肠黏膜组织病理学变化。结果缺血再灌注组小肠组织病理学改变较其他组明显;在再灌注0h、2h时B、C、D、E组血清中TNF—α、IL-1β、MDA含量均较A组显著升高（P〈0．05）;再灌注2h时C、D、E组血清中TNF—α、IL-1β、MDA含量均较B组明显降低（P〈0．05）,但C、D两组间差异无统计学意义;C、D组血清中TNF—α、IL-1β、MDA含量均较E组明显升高（P〈0．05）。结论血必净、维拉帕米能减轻大鼠小肠缺血再灌注损伤,二者联合用药有协同保护作用,效果更明昴。     

臭氧联合玻璃酸钠治疗膝骨性关节炎的疗效观察

[目的]观察医用臭氧(O3)联合玻璃酸钠(SH)治疗膝骨性关节炎的临床疗效。[方法]选择120例膝骨性关节炎患者,随机分为A、B、C三组,每组40例。其中A组第1周关节腔内注射15ml(35ug/ml)的医用臭氧,第2周注射玻璃酸钠25mg,第3周注射15ml(35ug/ml)的医用臭氧;B组关节腔内注射15ml/周的医用臭氧,每周1次,连续3次为1疗程;C组关节腔内注射玻璃酸钠25mg/周,每周1次,连续5次为1疗程,比较三组病例治疗前及治疗后1、2、3个月VAS值和治疗效果。[结果]三组患者治疗后VAS评分与治疗前相比均有降低(P0.01),在治疗后的第1、2、3个月同一时点,A组疼痛缓解最明显,VAS评分三组相比差异有统计学意义(P0.05,P0.01)。A组膝关节功能的优良率要高于对照组,差异有统计学意义(P0.05和P0.01)。全部患者未见明显的不良反应和副作用。[结论]医用臭氧联合玻璃酸钠治疗膝骨性关节炎能有效解除关节疼痛,改善关节活动度,临床疗效优于臭氧、玻璃酸钠单独应用。是一种治疗膝骨性关节炎的优势方法。     

金天格胶囊对绝经后膝骨关节炎OPN和MMP3表达的影响

目的：探讨金天格胶囊对绝经后膝骨关节炎患者血清中骨桥蛋白（OPN）和基质金属蛋白酶3（MMP－3）表达的影响。方法2013年1月－12月将180例绝经后膝骨关节炎妇女随机分为金天格胶囊组（ A组）、盐酸氨基葡萄糖胶囊组（ B组）、仙灵骨葆胶囊组（C组）,每组60例,采用酶联免疫吸附试验测定各组血清MMP－3、OPN、雌二醇（E2）、Ⅰ型胶原C端肽（CTX）和Ⅰ型胶原N端前肽（PINP）水平。结果 A组和B组在治疗后4周和6周JOA和VAS评分明显优于C组（P＜0．05）,B组在治疗后4周的MMP－3表达改善明显（P＜0．05）,优于其他两组。治疗后6周,A组OPN和MMP－3表达水平改善明显（P＜0．05）,优于其他两组。同时,A组和C组CTX和PINP水平明显改善（P＜0．05）,优于B组。结论金天格胶囊能有效改善绝经后骨性关节炎的症状,可能通过调节OPN和MMP3的复合体表达,改善关节软骨的功能实现这一目的。     

不同手术方式对关节软骨影响的实验研究

[目的]了解3种不同手术方式对活体关节软骨的影响。[方法]用光镜、扫描电镜及生物化学方法观察3种手术后不同时点兔膝关节软骨的结构及基质蛋白多糖的变化。[结果]3种手术对关节软骨都会造成损伤，使蛋白多糖的含量降低，暴露组造成不可逆性损伤，保护组和灌注组造成可逆性损伤，灌注组软骨损伤最轻、恢复最快。[结论]3种关节手术均会造成关节软骨损伤，关节灌注组的影响最小。     

Effects of calcitonin on subchondral trabecular bone changes and on osteoarthritic cartilage lesions after acute anterior cruciate ligament deficiency.

Because SBM may contribute to cartilage breakdown in OA, experimental OA was induced in dogs by transecting the anterior cruciate ligament of the knee and treating with either CT or a placebo. CT significantly reduced both SBM and cartilage lesions. This study supports the use of CT in the treatment of canine experimental OA. INTRODUCTION: Because subchondral bone remodeling (SBM) may contribute to cartilage breakdown in osteoarthritis (OA), we evaluated to what extend calcitonin (CT) might affect cartilage and bone changes in the early stages of canine experimental OA. MATERIALS AND METHODS: Twelve dogs underwent transection of the anterior cruciate ligament (ACLT) of the right knee. After ACLT, each animal received a daily nasal spray delivering either 400 U of CT (CT-treated group; n = 6) or a placebo (PL-treated group; n = 6). At day 84 after surgery, animals were killed, and cartilage changes were graded. BMD and volume fraction (BVF) were assessed by pQCT in different regions of interest (ROIs) of the subchondral cancellous bone of tibial plateaus (TPs).Statistics included a 2 x 2 factorial analysis with +/-CT as one factor and +/-ACLT as the other. RESULTS AND CONCLUSIONS: Nonoperated (N-OP) knees were normal in both groups. In the PL-treated group, ACLT knees all exhibited OA changes, which predominated in the medial knee compartment. Furthermore, compared with N-OP knees, the BMD and BVF of ACLT joints were both markedly reduced in medial TP but not in lateral TP. In contrast, in the CT-treated group, cartilage OA lesions of ACLT knees were significantly reduced, and there was no difference in BMD and BFV between N-OP and ACLT knees. These findings suggest that the loss of subchondral trabeculae contributes to cartilage breakdown, possibly by enhancing cartilage deformation on joint loading. By counteracting bone loss, CT reduced cartilage OA lesions, and thus, might be useful in the treatment of OA in cruciate-deficient dogs.     

不同细胞接种密度体外构建“自组装”工程化软骨的实验研究

[目的]探究以人骨髓间充质干细胞(humanbonemarrowmesenchymalstemcells,hMSCs)为种子细胞体外构建“自组装”工程化软骨对应的合理细胞接种密度.[方法]体外分离与培养hMSCs.用含100ng/ml生长分化因子5(growthdifferentiationfactor5,GDF-5)的软骨诱导液(chondrogenicmedium,CM)定向诱导培养第3代hMSCs,诱导3周后重悬细胞,分别以A组2.5×106/ml,B组5×106/ml,C组1x107/ml,D组2×107/ml四种细胞密度接种于2％琼脂糖包被的24孔板,每组设5个复孔.自组装培养3周后,对标本进行大体观察、组织学及免疫组化检测并进行生化分析,比较不同组标本的软骨生物学特性的差异.[结果]“自组装”培养3周后,各组都形成了软骨样组织团块,团块直径与湿重随细胞接种密度而增加.Bem评分结果显示C、D两组明显高于A、B两组(P＜0.05),且C组与D组间差异无统计学意义,Ⅱ型胶原免疫组化染色检测到C组与D组细胞外基质内有较强的阳性信号弥漫分布,蛋白多糖(GAG)含量C、D两组亦明显高于A、B两组(P＜0.05),且C组与D组间差异无统计学意义.[结论]在一定细胞接种密度范围内,“自组装”工程化软骨的生物学特性呈密度依赖性增加.以1×107/ml接种时,可以获得具有良好生物学特性的“自组装”工程化软骨.     

探讨~(99)Tc-MDP对青春期兔骨骼的影响

目的探讨99Tc-MDP短期使用对青春期新西兰兔骨骼生长的影响。方法选用11周的新西兰实验兔30只,分为5组,每组6只。A组为原始对照组,B、C为对照组,D、E两组给予99Tc-MDP静脉注射,每周1次,剂量为1mg/kg/5ml。D组于用药4周后与B组进行股骨X线摄片,对右侧股骨远端干骺端骺软骨线的宽度及相应部位的病理切片中软骨细胞的变化进行比较。将两组的兔子处死后进行胫骨和股骨长度的测量,并进行比较,以及血清BAP的对比。E组于用药后8周和C组进行与D组、B组相同的检测,同时与A组原始兔进行对比。结果D、E组股骨远端干骺端骺软骨线X线摄片较B、C对照组增粗,病理上D、E组骺软骨增殖区较B、C对照组明显增宽,而且细胞数量明显增多,分化相对活跃。实验组和对照组兔胫骨、股骨的长度,以及血清BAP存在一些差异。结论99Tc-MDP对于处于青春期的兔的骨骼生长可能存在一定的影响,但由于实验尚存在不足之处,需在今后的实验研究中进一步完善。     

Making the current non-surgical treatments for knee osteoarthritis more effective: Solutions from a diverse patient group

ObjectiveTo examine patient perceived solutions to barriers to effective non-surgical knee osteoarthritis (OA) treatments in a diverse racial/ethnic group.MethodsNominal groups were conducted with consecutive patients with knee OA at a medical center clinic, oversampling for African Americans with knee OA. Participants discussed potential solutions and rank-ordered their concerns.ResultsThirteen nominal groups with 46 knee OA patients were conducted with mean age, 60.8 years (standard deviation [sd], 10.0) and knee OA duration, 8.1 years (sd, 5.4); 22% were men, and 56% were African American. The following solutions were in the top three ranked solutions in 13 NGTs: (A) more research, effective and/or safer new medications/treatments, and joint cartilage restoration (8 groups; 15% votes [43/276]); (B) early diagnosis (2 groups; 7% votes [20/276]); (C) better and more effective communication (5 groups; 10% votes [29/276]); (D) public and patient education (4 groups; 8% votes [22/276]); (E) motivation and behavioral modification (4 groups; 9% votes [26/276]); (F) team approach (1 group; 1% votes [2/276]); (G) personalized medicine (6 groups; 8% votes [24/276]); (H) cheaper and more affordable medications and treatments (3 groups; 5% votes [15/276]).ConclusionsA diverse group of participants with knee OA identified several solutions to barriers to the effectiveness of current knee OA treatments. This new knowledge can inform the development and implementation of future interventions to improve the outcomes of people with knee OA.     

No loss of cartilage volume over three years in patients with knee osteoarthritis as assessed by magnetic resonance imaging

OBJECTIVE: Magnetic resonance imaging (MRI) has the potential to provide accurate quantification of structural changes in joint disease, with sensitivity to change, as it can provide direct visualization of the cartilage and bone. In this study, we investigated whether knee cartilage volume, as assessed by MRI, is sensitive to change over time in patients with osteoarthritis (OA). DESIGN: Sixteen patient volunteers (10 male, six female) with established OA of the knee were entered into the study and demographic data recorded. At baseline, 12 months and 37+/-2 months, patients underwent simple measures of disease severity, as well as extended weight-bearing AP knee X-rays. In addition the patient's index knee was imaged using MR at 1.0 T using a 3-D spoiled gradient-echo sequence with fat-suppression, repetition time 50 ms, echo time 11 ms, flip-angle 40 degrees, sagittal slice thickness 1.56 mm and in-plane pixel resolution 0.55 mm. Manual image segmentation was performed on all knee cartilage compartments and the respective cartilage volumes determined. RESULTS: Eleven of the original patients recruited completed the 3-year study. Radiographic features indicated that the majority had a spectrum of well-established OA at entry. The average decrease in medial tibiofemoral joint space width was 0.21+/-0.37 mm (mean+/-S.D.). Comparison of MR images at baseline and 37+/-2 months indicated little evidence of cartilage lesion shape or size change in any of the compartments. There was no significant MRI volume change in any of the knee cartilage compartments over the course of 1 year. The change in total knee cartilage volume, as measured by MRI, was a loss of only 1.6%, or 0.36+/-1.3 ml (mean+/-S.D.), over the 3 years. CONCLUSIONS: The failure to identify loss of cartilage volume over 3 years in this cohort of patients with established knee OA using MRI challenges the face validity of this endpoint to assess structural changes in OA.     

Increased knee joint loads during walking are present in subjects with knee osteoarthritis

OBJECTIVE: This study tests the hypothesis that the peak external knee adduction moment during gait is increased in a group of ambulatory subjects with knee osteoarthritis (OA) of varying radiographic severity who are being managed with medical therapy. Tibiofemoral knee OA more commonly affects the medial compartment. The external knee adduction moment can be used to assess the load distribution between the medial and lateral compartments of the knee joint. Additionally, this study tests if changes in the knee angles, such as a reduced midstance knee flexion angle, or reduced sagittal plane moments previously identified by others as load reducing mechanisms are present in this OA group. DESIGN: Thirty-one subjects with radiographic evidence of knee OA and medial compartment cartilage damage were gait tested after a 2-week drug washout period. Thirty-one normal subjects (asymptomatic control subjects) with a comparable age, weight and height distribution were also tested. Significant differences in the sagittal plane knee motion and peak external moments between the normal and knee OA groups were identified using t tests. RESULTS: Subjects with knee OA walked with a greater than normal peak external knee adduction moment (P=0.003). The midstance knee flexion angle was not significantly different between the two groups (P=0.625) nor were the peak flexion and extension moments (P> 0.037). CONCLUSIONS: Load reducing mechanisms, such as a decreased midstance knee flexion angle, identified by others in subjects with endstage knee OA or reduced external flexion or extension moments were not present in this group of subjects with knee OA who were being managed by conservative treatment. The finding of a significantly greater than normal external knee adduction moment in the knee OA group lends support to the hypothesis that an increased knee adduction moment during gait is associated with knee OA.     

The inhibition of subchondral bone resorption in the early phase of experimental dog osteoarthritis by licofelone is associated with a reduction in the synthesis of MMP-13 and cathepsin K

OBJECTIVE: To evaluate the morphological changes that take place in the subchondral bone and calcified cartilage zone in the experimental anterior cruciate ligament (ACL) dog model of osteoarthritis (OA) and analyze concomitant changes in the level of MMP-13 and cathepsin K, as well as examine the therapeutic effects of licofelone, a lipoxygenase (LO)/cyclooxygenase (COX) inhibitor, on these morphological and biochemical changes. METHODS: Experimental group 1 underwent sectioning of the ACL of the right knee with no active treatment (placebo group). Experimental groups 2 and 3 underwent sectioning of the ACL of the right knee and were administered therapeutic concentrations of licofelone (2.5 or 5.0 mg/kg/day p.o., respectively) for 8 weeks, beginning the day following surgery. Group 4 consisted of untreated dogs used as normal control. Specimens of subchondral bone including the calcified cartilage were selected from lesional and non-lesional areas of OA tibial plateaus. Specimens were processed for static morphometric analysis and immunohistochemical analysis for MMP-13 and cathepsin K. RESULTS: As indicated by a reduction in bone surface and trabecular thickness, a significant loss of subchondral bone occurred in OA dogs. These changes were associated with an increased level of MMP-13 synthesis by bone cells and an increase in the osteoclast population that stained strongly positive for cathepsin K and MMP-13. Changes were much more pronounced in the specimens taken from the lesional areas. Treatment with licofelone decreased, in a dose-dependent manner, the OA bone morphological changes at the same time it reduced the level of MMP-13 in bone cells and the number of cathepsin K and MMP-13 positive osteoclasts. CONCLUSIONS: Increased bone loss and bone resorption is associated with the development of OA cartilage lesions. Licofelone treatment was found to prevent the morphological and biochemical changes seen in early experimental OA effectively. These findings may help explain the mechanisms by which this drug could exert its possible effect on the development of OA.