AlexNet模型分级诊断膝关节软骨损伤

目的 基于3.0T MR常规序列图像及T2 mapping构建AlexNet模型,观察其用于分级诊断膝关节软骨损伤的价值。方法 针对131例膝关节软骨损伤患者及25名无膝关节病变体检者共选取2 500幅膝关节MRI,包括常规序列图像及T2 mapping,建立AlexNet模型;对比观察人工阅片、SqueezeNet模型及AlexNet模型用于分级诊断膝关节软骨损伤的效能。结果 AlexNet模型分级诊断膝关节软骨损伤的整体效能高于人工阅片及SqueezeNet模型（P均<0.05）;其分级诊断膝关节软骨损伤的准确率为97.50%,诊断Ⅰ级损伤精确度、召回率及F1-score分别为99.66%、98.67%及99.16%,Ⅱ级损伤为94.70%、95.33%及95.02%,Ⅲ级损伤为95.61%、94.33%及94.97%,Ⅳ级损伤为98.04%、100%及99.01%。结论 AlexNet模型用于分级诊断膝关节软骨损伤效能较佳。     

膝关节骨性关节炎腓骨截骨前后软骨代谢产物变化的研究

目的:探讨膝关节骨性关节炎患者腓骨截骨前后软骨代谢中的Ⅱ型胶原3/4片段C末端裂解表位(C-terminal cleavage epitope of typeⅡcollagen 3/4 fragment,Col2-3/4Clong mono or C2C),Ⅱ型胶原羧基端端肽(carboxyl-terminal telopeptide of typeⅡcollagen,CTX-Ⅱ)及膝关节功能变化。方法:自2019年1月至2020年3月采用腓骨截骨术治疗65例内侧疼痛的膝关节骨性关节炎患者,其中男25例,女40例;年龄44~70(56.20±10.05)岁;Kellgren-Lawrence分级,Ⅰ级25例,Ⅱ级19例,Ⅲ级17例,Ⅳ级4例。分别于截骨前、截骨后6个月检测膝关节液的CTX-Ⅱ、C2C水平以及血清白细胞介素-1β(interleukin-1β,IL-1β),肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)水平。采用疼痛视觉模拟评分(visual analogue scale,VAS)评估患者疼痛缓解情况,采用美国膝关节协会评分(Keen Society Score,KSS)和美国特种外科医院(Hospital for Special Surgery,HSS)膝关节评分评估膝关节功能恢复情况。结果:65例均获得随访,时间6~18(12.4±3.6)个月。截骨后6个月,VAS、KSS、HSS评分优于截骨前(P<0.05)。截骨后6个月血清IL-1β、TNF-α、膝关节液CTX-Ⅱ和C2C均低于截骨前(P<0.05)。结论:腓骨截骨可缓解膝关节骨性关节炎患者疼痛,维持关节受力平衡,减轻患者机体炎症反应,改善软骨代谢状态,减少关节软骨的分解,使CTX-Ⅱ、C2C水平下调,有利于退变关节软骨的再生,促进膝关节功能恢复。     

关节镜下软骨成形术在胫骨高位截骨术治疗内翻型膝骨关节炎中的应用

目的 探讨关节镜下软骨成形术结合胫骨高位截骨术（high tibial osteotomy,HTO）治疗内翻型膝骨关节炎的临床疗效。方法 选取2018年5月至2020年5月我科收治的39例施行HTO的内翻型膝骨关节炎病人,其中在关节镜下对损伤的软骨行成形术的18例纳入观察组,另外21例未在关节镜下对软骨损伤进行处理的病人作为对照组,比较两组病人手术前后的西安大略和麦克马斯特大学（WOMAC）关节炎指数、疼痛视觉模拟量表（VAS）评分、胫骨近端内侧角（medial proximal tibial angle,MPTA）和股胫角（femora tibial angle,FTA）,以及两组病人手术前后屈伸角度和屈曲达90°所用时间。结果 两组病人手术后WOMAC指数、VAS评分和FTA均较术前显著降低,MPTA较术前明显增大,与术前比较,差异有统计学意义（P＜0.05）。另外,两组病人之间术前和术后随访中,MPTA、FTA并无明显差异（P＞0.05）,而观察组术后WOMAC指数及VAS评分显著低于对照组（P＜0.05）。观察组术后末次随访时屈曲和伸直角度明显优于对照组（P＜0.05）,并且观察组屈曲角度达90°所用时间明显少于对照组（P＜0.05）。结论 关节镜下软骨成形术结合HTO治疗内翻型膝骨关节炎,疗效肯定,可以显著缓解病人疼痛症状,使病人能够早期高效地开始功能锻炼,获得更好的功能状态。     

胫骨高位截骨术治疗膝骨关节炎的临床疗效评估及对关节软骨再生的影响

目的 评估胫骨高位截骨术（high tibial osteotomy, HTO）对膝骨关节炎病人临床症状改善及软骨再生的影响。方法 采用回顾性研究方法,选取2016年4月至2017年6月在我院确诊为膝骨关节炎并接受HTO手术的病人42例（42膝）,评估上述病人手术前后的膝关节西安大略和麦克马斯特大学骨关节炎指数（the Western Ontario and McMaster Universities Arthritis Index, WOMAC）、膝关节Lysholm评分、下肢髋-膝-踝（hip-knee-ankle, HKA）角及膝关节镜下图片。结果 所有病人均手术顺利,术后无感染、骨不连、神经血管损伤等严重并发症。随访时间为（12.64±1.32）个月。病人膝关节WOMAC评分由术前的（45.26±10.27）分改善至末次随访的（0.76±0.66）分,Lysholm评分从术前的（57.93±11.98）分改善至末次随访的（95.21±2.46）分,HKA角由术前171.26°±5.20°改善至末次随访的181.26°±1.65°,手术前后的数值比较,差异均有统计学意义（P均＜0.05）。术前、第2次探查关节镜图片评估显示97.62%（41/42）的膝关节出现术后软骨再生。结论 HTO治疗早、中期膝骨关节炎的疗效肯定,对病人下肢力线纠正明显,同时对膝骨关节股骨内侧髁和胫骨内侧平台的软骨再生有积极影响。     

ARCO 2-4期股骨头坏死MR征象对Harris评分影响分析

目的:分析并确定ARCO 2-4期股骨头坏死(osteonecrosis of femoral head,ONFH)对Harris评分有影响意义的MR征象。方法:回顾性分析2019年1月至2020年6月34例行常规MR、T2 mapping、3D-SPACE序列检查及Harris评分的ARCO 2-4期ONFH患者,排除3例,最终纳入31例,男23例,女8例,年龄18~62(40.0±10.8)岁;其中21例为双侧ONFH,共计52个ONFH,ARCO 2期17个,ARCO 3期24个,ARCO 4期11个。在医院数字影像信息系统(picture archiving and communication system,PACS)对MR影像征象(股骨头塌陷深度、ONFH指数、骨髓水肿、股骨头骨质增生、软骨损伤分级、软骨T2值及关节积液)进行评估及测量,在Siemens后处理工作站计算软骨定量参数T2值并测量。采用Pearson相关分析评估MR各征象与Harris评分的相关性,采用多重线性回归分析评估与Harris评分有相关性的MR征象对Harris评分的影响。结果:Pearson 相关分析显示股骨头塌陷深度(r=-0.563,P=0.000)、软骨损伤分级(r=-0.500,P=0.000)及关节积液(r=-0.535,P=0.000)与Harris评分呈负相关。多重线性回归分析显示关节积液(β=-6.198,P=0.001)、股骨头塌陷深度(β=-4.085,P=0.014)对Harris评分呈负相关。结论:关节积液、股骨头塌陷深度对Harris评分有显著的负向影响关系,建议影像医师常规对股骨头塌陷深度、关节积液进行定量及等级评估,以高效精准地辅助临床诊疗。     

复位固定联合韧带修复治疗伴内侧髌股韧带及骨软骨损伤的创伤性髌骨脱位

目的 分析采用可吸收棒复位固定膝关节骨软骨骨折联合内侧髌股韧带（medial patellofemoral ligament, MPFL）修复治疗伴有MPFL及骨软骨损伤的创伤性髌骨脱位的临床效果。方法 对2013年1月至2017年1月我院收治81例伴有MPFL及膝关节骨软骨损伤的创伤性髌骨脱位病人进行回顾性分析,其中男29例,女52例;年龄为16~33岁（平均17.7岁）。采用膝关节骨软骨骨折固定联合MPFL修复治疗的65例纳入固定修复组,采用膝关节骨软骨骨折清理联合MPFL修复治疗的16例纳入清理修复组。收集两组病人术后的膝关节功能障碍、再脱位的发生率及膝关节疼痛情况等,并比较两组病人术前及术后1年的国际膝关节文献委员会（the international knee documentation committee, IKDC）膝关节评分和Lysholm评分。结果 81例病人平均随访28.6个月。固定修复组出现2例（2/65,3.08%）术后膝关节功能障碍,3例（3/65,4.62%）再脱位;清理修复组有1例（1/16,6.25%）再脱位,4例（4/16,25.00%）膝前疼痛。固定修复组的IKDC评分由术前的（43.1±13.2）分提高到术后的（83.8±6.3）分,Lysholm评分由术前的（48.3±6.2）分提高到术后的（87.1±9.8）分;清理修复组的IKDC得分由术前的（42.3±9.8）分提高到术后的（80.2±3.2）分,Lysholm评分由术前的（49.5±5.4）分提高到术后的（81.3±5.4）分。两组手术前后的IKDC、Lysholm评分差异均有统计学意义（P均＜0.05）,但两组间的IKDC、Lysholm评分差异均无统计学意义（P均＞0.05）。结论 可吸收棒复位固定骨软骨骨折联合MPFL修复是治疗伴有MPFL及膝关节骨软骨损伤的创伤性髌骨脱位的有效方法。     

自体骨软骨马赛克移植成形术后膝关节供区部位发病率的系统评价

目的：对自体骨软骨马赛克移植成形术后膝关节供区部位发病率进行概述。方法：通过计算机检索2010年1月至2021年4月20日PubMed,EMbase,万方医学网和中国知网发表的评估马赛克成形术后膝关节供区发病率的相关研究文献,根据纳入与排除标准进行文献筛选,质量评价及数据提取,对移植的骨软骨柱个数和大小与供区发病率之间的相关性进行研究。结果：共纳入13篇文献,共661例患者。统计分析结果表明马赛克成形术后膝关节供体部位发病率为8.6%（57/661）,最常见的供区发病率主诉是膝关节疼痛感4.2%（28/661）。供体数目与术后供区发病率之间不存在相关性（P=0.424,N=10）;供体直径大小与术后供区发病率之间同样不存在相关性（P=0.699,N=7）。结论：自体骨软骨移植/马赛克成形术中的骨软骨柱采集通常会导致相当大的供区发病率8.6%（57/661）,最常见的供区发病率主诉是膝关节疼痛感,且供体部位发病率与骨软骨柱的数量和大小之间并没有明显的相关性,因此临床上对供体任何部位,数量和大小骨软骨骨柱的采集,都应该意识到其潜在的供体部位发病风险。     

影响症状性外侧盘状半月板术后疗效的相关危险因素分析

目的：探讨关节镜治疗症状性外侧盘状半月板（discoid lateral meniscus,DLM）术后疗效的影响因素。方法：回顾性分析2008年9月至2015年9月于四川大学华西医院运动医学中心诊断为症状性DLM并行关节镜手术治疗的患者。膝关节功能由Lysholm评分系统进行评估,根据评分结果分为优（≥ 90分）、良（80~89分）、可（70~79分）、差（<70分）。收集患者临床资料,包括性别、手术年龄、体质量指数、工作强度、症状持续时间、膝关节创伤史、受累膝关节侧别、DLM分型、DLM损伤类型、DLM损伤部位、内侧半月板损伤、膝关节软骨损伤部位及损伤程度、Kellgren-Lawrence （K-L）分级、手术方式、末次随访时间共16项拟研究因素。根据数据类型,单因素分析采用Kruskall-Wallis秩和检验或χ²检验,多因素分析采用有序Logistic回归模型。单因素分析具有统计学意义的因素纳入多因素分析模型,最终获得影响症状性DLM术后疗效的独立危险因素。结果：根据纳入排除标准,共纳入502例患者。末次随访的Lysholm功能分级高于术前（P<0.001）。单因素分析显示：在Lysholm各功能分级之间,性别、体质量指数、工作强度、膝关节创伤史、手术年龄、症状持续时间、内侧半月板损伤、K-L分级、手术方式、膝关节软骨损伤部位及程度的差异均有统计学意义（P<0.05）。有序Logistic回归分析显示：女性是影响术后疗效的独立危险因素（P=0.002,OR=0.370）;体质量指数（P=0.007,OR=0.894）,工作强度（P=0.004,OR=0.525）,手术年龄（P<0.001,OR=0.953）,症状持续时间（P<0.001,OR=0.989）,膝关节软骨损伤程度（P=0.016,OR=0.631）与Lysholm膝关节功能分级呈负相关。结论：关节镜是治疗症状性DLM安全、有效的方法,性别、体质量指数、工作强度、手术年龄、症状持续时间以及膝关节软骨损伤程度是症状性DLM术后疗效的独立影响因素。     

How to diagnose isolated articular cartilage lesions of the knee in a consulting room

Abstract In order to clinically diagnose articular cartilage lesions of the knee in a medical examination, 121 knees (117 cases) with isolated lesions were investigated. Lesions of the patella (PAT), facies patellaris (F-PAT), lateral femoral condyle (LFC), lateral tibial plateau (LTP), medial femoral condyle (MFC), and medial tibial plateau (MTP) were found in 15, 10, 9, 57, 24, and 6 knees, respectively. The lesions often occurred in athletes, but many cases with lesions did not have a history of trauma. Giving way, pain in maximal flexion, pain after exercise, and pseudolocking were relatively common symptoms. Atrophy of the thigh on the involved side was not severe. Mild limitations in both extension and flexion were often found. Hydrarthrosis was frequent in cases with F-PAT, LFC, and MFC lesions. Valgus alignment was found in LTP lesions, while varus alignment was found in MFC and MTP lesions. Findings of fibrillation in PAT, flaps, deep defects, and softening in F-PAT and MFC, deep defects in LFC, and softening and fissuring in LTP were often seen during arthroscopy. Cartilage lesions such as softening were also thought to be related to the symptoms. Increases in joint fluid may suggest lesions in F-PAT, LFC or MFC where deep and wide lesions often occur. Cases with valgus alignment may have LTP lesions and those with varus alignment may have MFC or MTP lesions.     

Topical administration of the nitric oxide donor glyceryl trinitrate modifies the structural and biomechanical properties of ovine articular cartilage

Objective: To examine the effect of topical administration of glyceryl trinitrate (GTN), an exogenous nitric oxide (NO) donor, on the structural and biomechanical properties of uncalcified articular cartilage (UCC) in aged ewes.Design: Twelve ewes were used for this study. Six of these were treated with 2% GTN ointment (0.7 mg/kg) twice per week (GTN), and the remaining six were used as normal controls (NOC). After sacrifice at 26 weeks, dynamic biomechanical indentation testing and thickness determination (by needle penetration) were performed on tibial plateau articular cartilage at 18 locations. Using histological sections prepared from the lateral and medial femoral condyles (LFC, MFC) and tibial plateau (LTP, MTP), the thickness of UCC, cartilage proteoglycan content (intensity of toluidine blue staining; LFC, MFC only), and collagen birefringence (LTP, MTP, LFC only) were quantified by computer-assisted image analysis.Results: Phase lag of tibial plateau cartilage was reduced in GTN sheep relative to NOC (mean of all testing locations 11.0±1.9° vs 12.1±2.3°; P=0.0001). GTN treatment also globally reduced UCC thickness across the joint (ANOVA for all measured zones, P<0.0001). UCC thinning was most pronounced in the MFC (P=0.025) and LTP (P=0.0002). Proteoglycan content was reduced in the MFC(P=0.019), while collagen birefringence was increased in superficial cartilage zones of the LTP.Conclusions: NO donation via topical administration of GTN to normal ewes reduced the thickness and phase lag of femoro-tibial articular cartilage, suggesting a disturbance in chondrocyte metabolism. Regional alterations of collagen organisation and proteoglycan content were consistent with this interpretation.     

Editorial Commentary: Knee Lateral Femoral Osteochondral Allografts Are Not Recommended for Medial Femoral Condylar Defects: If the Shoe Doesn’t Fit,Don’t Wear It!

Treatment of large articular cartilage defects of the knee is challenging, particularly in young, high-demand patients. Osteochondral allograft (OCA) transplantation is a viable treatment option, providing fully mature articular cartilage during a single operation while avoiding donor site morbidity. Indications are symptomatic, full-thickness articular cartilage defects >3 cm². Contraindications include a “kissing” lesion of the corresponding articular cartilage surface, uncorrected ligamentous instability, malalignment, peripheral osteophytes, joint-space narrowing, or absence of >50% of the meniscus in the affected compartment. Matching for size and contour is crucial; therefore, we use medial femoral condyle (MFC) allografts for MFC lesions and lateral femoral condyle (LFC) allografts for LFC lesions, and do not recommend LFC grafts for the MFC. Survival rates are 78.7% and 72.8% at 10 and 15 years, respectively.     

Modification of articular cartilage and subchondral bone pathology in an ovine meniscectomy model of osteoarthritis by avocado and soya unsaponifiables (ASU)

OBJECTIVE: To examine the effect of an oral preparation of avocado and soya unsaponifiables (ASU) on the development of joint pathology in an ovine model of osteoarthritis (OA), using computer-assisted histomorphometric methods. DESIGN: OA was induced in ovine knee joints by bilateral lateral meniscectomy (N=32). ASU (900 mg/weekday) was given orally to half the group (MenX+ASU), the remainder receiving placebo (MenX). Sixteen animals were used as non-operated controls (NOC). At 3 and 6 months post-meniscectomy, histological sections from the medial and lateral femoral condyles (MFC, LFC), tibial plateaux (MTP, LTP) and trochlear groove (TG) were prepared from all joints. Sections were scored using traditional histopathological scales, and computerized image analysis, measuring total cartilage area, uncalcified cartilage (UCC) and subchondral bone plate (SCP) thickness, and intensity of articular cartilage toluidine blue staining (mean greyscale intensity, black=255) as an index of proteoglycan (PG) content. RESULTS: Computerized image analysis showed significant histological differences not detectable by traditional scoring methods. ASU-treated animals at 6 months showed reduced loss of toluidine blue stain in the MTP (P=0.015) and LTP (P=0.001), and significantly greater staining in the TG than either placebo or NOC groups (P=0.011). UCC thickness increased after meniscectomy, but tended to be highest in ASU-treated animals, significantly so in the middle zone of the LFC (MenX+ASU: 1.03+/-0.21mm vs MenX: 0.79+/-0.14 mm, P=0.018; NOC: 0.77+/-0.17 mm). Lateral compartment SCP thickness increased post-meniscectomy but was increased significantly less in the inner zone of the LTP in ASU-treated sheep (MenX+ASU: 1.37+/-0. 23 mm vs MenX: 1.68+/-0.28 mm, P=0.033; NOC=1.22+/-0.33 mm). CONCLUSIONS: In this model ASU treatment following meniscectomy appeared to confer a subtle but statistically significant protective effect on articular cartilage. Although the drug failed to prevent focal cartilage lesions, characteristic of this model, histomorphometric analysis demonstrated greater PG content and UCC thickness in adjacent joint regions of ASU-treated animals. In addition, a statistically significant reduction of subchondral bone sclerosis was noted in the LTP region of the drug-treated group. An anabolic effect on chondrocytes, resulting in the stimulation of matrix production in regions distant to the insult, was also suggested by the data. These findings support other studies which have proposed that ASU may exhibit disease-modifying anti-OA activity.     

The nitric oxide donor glyceryl trinitrate increases subchondral bone sclerosis and cartilage degeneration following ovine meniscectomy

AIM: To examine the effect of glyceryl trinitrate (GTN), a nitric oxide (NO) donor compound, on the concurrent progression of cartilage and subchondral bone changes in an ovine meniscectomy model of osteoarthritis (OA). METHODS: Bilateral lateral meniscectomy (MX) was performed on 12 ewes to induce OA. Six were treated with topical GTN (0.7mg/kg twice weekly) (MX+GTN). Six other sheep formed non-operated controls (NOC). After sacrifice at six months, the subchondral bone density (BMD) of the lateral and medial femoral condyles (LFC, MFC) and tibial plateau (LTP, MTP) was assessed by DEXA. Dynamic biomechanical testing was performed across the MTP and LTP. Histological sections from each region were scored qualitatively and the thickness of the subchondral bone plate (SCB) was determined by image analysis. RESULTS: MX+GTN displayed significantly greater SCB thickness relative to MX in the LFC (mean increase +88% and +42%, respectively) and the MFC. SCB BMD was 10-12% greater in MX+GTN relative to MX in the LFC, LTP and MTP. MX+GTN sheep also showed greater increases in some histopathology variables, greater central erosion of the LTP, and changes in dynamic stiffness (decreased) and phase lag (increased) in the outer zone of the LTP. CONCLUSIONS: Treatment with GTN significantly increased subchondral bone thickness and density during subchondral remodelling following meniscectomy. In addition, it slightly but significantly worsened degeneration of cartilage structure and function. These results suggest that clinical use of GTN may accelerate both cartilage degeneration and subchondral bone sclerosis if used in the presence of OA, and demonstrate that NO has the potential be an important mediator of the subchondral bone changes seen in OA.     

Hyaluronic acid and chondroitin sulfate content of osteoarthritic human knee cartilage: Site‐specific correlation with weight‐bearing force based on femorotibial angle measurement

This study analyzed glycosaminoglycan (GAG) content in specific compartments of the knee joint to determine the impact of malalignment and helped refine indications for osteotomy. To assess malalignment, the radiological femorotibial angle (FTA) was measured and knee joints were also graded for OA severity with the Kellgren/Lawrence (K/L) classification. Cartilage samples were obtained from 36 knees of 32 OA patients undergoing total knee replacement surgery. Explants were harvested from the medial femoral condyle (MFC), lateral femoral condyle (LFC), patellar groove (PG), and lateral posterior femoral condyle (LPC). Concentrations of hyaluronic acid (HA) and chondroitin sulfate (CS) were measured by high‐performance liquid chromatography (HPLC). With OA severity, the average FTA significantly increased. HA and CS content in MFC was negatively correlated with radiographic FTA. In LFC, HA ratio, which is HA content in lateral condyle divided by medial condyle and chondroitin 6 sulfate, increased until about 190° FTA. Importantly, at >190° these contents were significantly decreased. HA and CS content of the femoral condyle shows topographic differences that are related to OA grade and weight‐bearing force based on FTA. The clinical relevance is that osteotomy may not be indicated for patients with severe varus (>190°) abnormalities. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:1194–1198, 2008     

Biochemical, biomechanical and histological properties of osteoarthritic porcine knee cartilage: implications for osteochondral transplantation

Introduction Cartilage lesions of the knee joint are frequently observed during arthroscopy and when surgical intervention is required, osteochondral autograft procedures are an established method of treatment. Frequently lesions are located on the medial femoral condyle (MFC), and typical donor locations for osteochondral grafts include the medial and lateral patellar groove. This technique provides good results, even when the quality of cartilage transplanted from an osteoarthritic joint is doubtful. This study characterizes biological, biomechanical and histological properties of cartilage explants from the patellar groove harvested from osteoarthritic joints. Materials and methods Cylindrical cartilage explants were harvested from the arthritic areas of the MFC as well as normal appearing regions of the medial and lateral patellar groove from porcine joints revealing various grades of osteoarthritis. Matrix synthesis rates were determined, and explants were investigated by mechanical testing and histology. Results Articular cartilage obtained from the typical donor areas of the medial and lateral patellar groove provided constant enhanced material properties, matrix synthesis rates and histological appearance compared to samples from the arthritic lesions of the MFC, even in joints with end-stage osteoarthritis of the MFC. No significant difference was found between patellar groove cartilage samples harvested from joints with different stages of osteoarthritis. Conclusion Our findings demonstrate that healthy appearing cartilage from the patellar groove does not undergo significant alterations in material properties due to the arthritic milieu present in osteoarthritic joints. Accordingly these locations provide a source of functional tissue for transplant procedures even in joints with end-stage osteoarthritis.     

Ovariectomy alters the structural and biomechanical properties of ovine femoro-tibial articular cartilage and increases cartilage iNOS

OBJECTIVE: To examine the effect of oestrogen depletion produced by surgical ovariectomy on the structural and biomechanical properties of ovine femoro-tibial articular cartilage (AC), and the production of inducible nitric oxide synthase (iNOS) and nitrotyrosine by these tissues. METHODS: Six aged ewes were surgically ovariectomised (OVX), while six were used as unoperated controls. Dynamic biomechanical indentation testing of tibial plateau AC was performed at 26 weeks post-op. Histological sections of medial tibial plateau and lateral tibial plateau (LTP), medial and lateral femoral condyles (MFC, LFC) and patellar AC were examined for histopathology, toluidine blue staining intensity, and patterns of collagen birefringence intensity. Immunoreactivity for iNOS and nitrotyrosine was assessed in full-thickness biopsy plugs of LFC and patellar AC, and patellar AC explants were cultured to determine in vitro NO release. RESULTS: Phase lag was reduced overall in LTP-AC of OVX sheep (10.9+/-2.2 degrees vs 12.1+/-2.3 degrees ; P<0.0001). Cartilage thickness was reduced in the LTP of OVX sheep (P=0.0002), in association with localised changes in dynamic shear modulus. Toluidine blue staining intensity was reduced in the patella, LFC, and MFC. Histological examination revealed greater histopathology scores in the MFC of OVX animals, and altered collagen birefringence intensity plots in the LTP. Immunostaining for iNOS was increased in patella AC (P=0.008), whilst nitrotyrosine immunoreactivity was increased in patella (P=0.03) and LFC (P<0.0001) AC. NO release by patellar AC explants was also elevated. CONCLUSIONS: Oestrogen depletion induced by OVX caused regional thinning of femoro-tibial cartilage, with biomechanical and histological changes suggestive of a disturbance in the content and/or structural organisation of the proteoglycan and collagen macromolecular assembly. The observed up-regulation of cartilage iNOS suggests a possible mechanism for these matrix changes.