The relationship between specific tissue lesions and pain severity in persons with knee osteoarthritis

SummaryIntroductionPain is the most common symptom in knee osteoarthritis (OA), a leading cause of chronic disability, and a major source of the disability attributable to OA in general. Pain severity in knee OA is variable, ranging from barely perceptible to immobilizing. The knee lesions that contribute to pain severity have received little attention.ObjectiveTo examine whether worse pathology of specific knee tissues – i.e. cartilage, bone (attrition, cysts, bone marrow lesions, and osteophytes), menisci (tears and subluxation), ligaments, and synovium (synovitis/effusion) – is associated with more severe knee pain.MethodsOne hundred and forty-three individuals were recruited from the community with primary (idiopathic) knee OA, with definite tibiofemoral osteophytes in at least one knee, and at least some difficulty with knee-requiring activity. Knee magnetic resonance (MR) images were acquired using coronal T1-weighted spin-echo (SE), sagittal fat-suppressed dual-echo turbo SE, and axial and coronal fat-suppressed, T1-weighted 3D-fast low angle shot (FLASH) sequences. The whole-organ magnetic resonance imaging (MRI) scoring (WORMS) method was used to score knee tissue status. Since summing tissue scores across the entire joint, including regions free of disease, may dilute the ability to detect a true relationship between that tissue and pain severity, we used the score from the worst compartment (i.e. with the poorest cartilage morphology) as our primary approach. Knee pain severity was measured using knee-specific, 100mm visual analogue scales. In analyses to evaluate the relationship between knee pain severity and lesion score, median quantile regression was used, adjusting for age and body mass index (BMI), in which a 95% CI excluding 0 is significant.ResultsThe increase in median pain from median quantile regression, adjusting for age and BMI, was significant for bone attrition (1.91, 95% confidence interval (CI) 0.68, 3.13), bone marrow lesions (3.72, 95% CI 1.76, 5.68), meniscal tears (1.99, 95% CI 0.60, 3.38), and grade 2 or 3 synovitis/effusion vs grade 0 (9.82, 95% CI 0.38, 19.27). The relationship with pain severity was of borderline significance for osteophytes and cartilage morphology and was not significant for bone cysts or meniscal subluxation. Ligament tears were too infrequent for meaningful analysis. When compared to the pain severity in knees with high scores for both bone attrition and bone marrow lesions (median pain severity 40mm), knees with high attrition alone (30mm) were not significantly different, but knees with high bone marrow lesion without high attrition scores (15mm) were significantly less painful.ConclusionIn persons with knee OA, knee pain severity was associated with subarticular bone attrition, bone marrow lesions, synovitis/effusion, and meniscal tears. The contribution of bone marrow lesions to pain severity appeared to require the presence of bone attrition

Clinical Significance of Cartilage Biomarkers for Monitoring Structural Joint Damage in Rheumatoid Arthritis Patients Treated with Anti-TNF Therapy

PURPOSE: With the current use of biologics in rheumatoid arthritis (RA), there is a need to monitor ongoing structural joint damage due to the dissociation of articular cartilage damage from disease activity of RA. This study longitudinally analyzed levels of serum cartilage biomarkers during 54 weeks of infliximab therapy, to evaluate the feasibility of biomarkers for monitoring structural joint damage. METHODS: Subjects comprised 33 patients with early RA and 33 patients with established RA. All patients received 3 mg/kg of infliximab and methotrexate for 54 weeks. Levels of the following serum cartilage markers were measured at baseline and at weeks 14, 22, and 54: hyaluronan (HA); cartilage oligometric matrix protein (COMP); type II collagen (CII)-related neoepitope (C2C); type II procollagen carboxy-propeptide (CPII); and keratin sulfate (KS). Time courses for each biomarker were assessed, and relationships between these biomarkers and clinical or radiographic parameters generally used for RA were investigated. RESULTS: Levels of CRP, MMP-3, DAS28-CRP, and annual progression of TSS were improved to similar degrees in both groups at week 54. HA and C2C/CPII were significantly decreased compared to baseline in the early RA group (p<0.001), whereas HA and COMP, but not C2C/CPII, were decreased in the established RA group. Strikingly, serum C2C/CPII levels were universally improved in early RA, regardless of EULAR response grade. Both ΔHA and ΔC2C/CPII from baseline to week 54 correlated significantly with not only ΔCRP, but also ΔDAS28 in early RA. Interestingly, when partial correlation coefficients were calculated by standardizing CRP levels, the significant correlation of ΔHA to ΔDAS28 disappeared, whereas correlations of ΔC2C/CPII to ΔDAS28, ΔJNS, and ΔHAQ remained significant. These results suggest a role of ΔC2C/CPII as a marker of ongoing structural joint damage with the least association with CRP, and that irreversible cartilage damage in established RA limits restoration of the C2C/CPII level, even with tight control of joint inflammation. CONCLUSION: The temporal course of C2C/CPII level during anti-TNF therapy indicates that CII turnover shifts toward CII synthesis in early RA, but not in established RA, potentially due to irreversible cartilage damage. ΔC2C/CPII appears to offer a useful marker reflecting ongoing structural joint damage, dissociated from inflammatory indices such as CRP and MMP-3

Varus thrust and knee frontal plane dynamic motion in persons with knee osteoarthritis

SummaryObjectiveVarus thrust visualized during walking is associated with a greater medial knee load and an increased risk of medial knee osteoarthritis (OA) progression. Little is known about how varus thrust presence determined by visual observation relates to quantitative gait kinematic data. We hypothesized that varus thrust presence is associated with greater knee frontal plane dynamic movement during the stance phase of gait.MethodsParticipants had knee OA in at least one knee. Trained examiners assessed participants for varus thrust presence during ambulation. Frontal plane knee motion during ambulation was captured using external passive reflective markers and an 8-camera motion analysis system. To examine the cross-sectional relationship between varus thrust and frontal plane knee motion, we used multivariable regression models with the quantitative motion measures as dependent variables and varus thrust (present/absent) as predictor; models were adjusted for age, gender, body mass index (BMI), gait speed, and knee static alignment.Results236 persons [mean BMI: 28.5 kg/m2 (standard deviation (SD) 5.5), mean age: 64.9 years (SD 10.4), 75.8% women] contributing 440 knees comprised the study sample. 82 knees (18.6%) had definite varus thrust. Knees with varus thrust had greater peak varus angle and greater peak varus angular velocity during stance than knees without varus thrust (mean differences 0.90° and 6.65°/s, respectively). These patterns remained significant after adjusting for age, gender, BMI, gait speed, and knee static alignment.ConclusionVisualized varus thrust during walking was associated with a greater peak knee varus angular velocity and a greater peak knee varus angle during stance phase of gait