Disease Severity In Osteoarthritis Research Articles

Radiographic severity of knee osteoarthritis is conditional on interleukin 1 receptor antagonist gene variations

BackgroundA lack of biomarkers that identify patients at risk for severe osteoarthritis (OA) complicates development of disease-modifying OA drugs.ObjectiveTo determine whether inflammatory genetic markers could stratify patients with knee OA...

The Relationship of Self-Reported Pain and Functional Impairment to Gait Mechanics in Overweight and Obese Persons With Knee Osteoarthritis

Nebel MB, Sims EL, Keefe FJ, Kraus VB, Guilak F, Caldwell DS, Pells JJ, Queen R, Schmitt D. The relationship of self-reported pain and functional impairment to gait mechanics in overweight and obese persons with knee osteoarthritis. Objective To examine the degree to which 2 commonly used measures of pain and disability, the Arthritis Impact Measurement Scales (AIMS) and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), relate to objective gait measurements. Design A descriptive study of the influence of self-reported pain and perceived functional impairment on gait mechanics in osteoarthritic adults. Setting A university clinical research laboratory. Participants Overweight/obese adults with radiographic knee osteoarthritis (OA) as well as pain and disability associated with the disease (N=179). Interventions Not applicable. Main Outcome Measures The AIMS and WOMAC were administered to determine self-report measures of pain and disability. Speed, stride length, support time, knee angle, and peak vertical force (PVF) were determined from 3-dimensional kinematic and kinetic data collected on subjects walking at self-selected normal and fast speeds. Anthropometric data and radiographic levels of OA were also collected. Results Pearson correlation analysis showed that the AIMS physical disability score was inversely correlated with speed, stride length, and knee range of motion at both speeds and PVF at the fast speed. The WOMAC function score was inversely correlated with speed and stride length at both speeds and with PVF at fast speed. The WOMAC pain score was inversely correlated with speed and PVF at the fast speed. Regression analysis revealed that the AIMS physical disability score and body mass index accounted for the greatest variation in speed at the normal speed. Overall, AIMS physical disability and WOMAC function explained a larger proportion of variance in gait mechanics than radiographic measures of OA disease severity. Conclusions Taken together, the results suggest that the AIMS physical disability and WOMAC function scores are associated with some important measures of gait impairment.

Objective assessments of medial osteoarthritic knee severity by MRI: new computer software to evaluate femoral condyle contours

An irregular contour of the medial femoral condyle (MFC) on magnetic resonance imaging (MRI) appears to indicate the severity of medial-type knee osteoarthritis (OA). The purpose of this study was to establish a system to enable objective assessments of OA knee severity using newly developed software that semi-automatically measures irregularity of the MFC. (1) We evaluated 48 patients aged 50-83 years with 55 knees of medial-type OA. The following scores were recorded: Lysholm score, visual analogue scale (VAS) and the Japanese Knee Osteoarthritis Measure (JKOM). MFC irregularity was automatically calculated by newly programmed computer software. Four parameters for condyle irregularity were calculated: (a) the average thickness of the contour (ATC), (b) the ratio of the upper surface length to the lower surface length of the contour (RUL), (c) average squared thickness of the contour (ASTC) and (d) standard deviation of the contour thickness (SDC). (2) Nine knees that underwent total knee arthroplasty were further analysed histopathologically and compared with irregularity score. Statistically, the RUL and SDC were significantly correlated with the Lysholm score, VAS and JKOM, with good reliability. Histological examinations showed that an irregular contour reflected the density of cystic lesions formed in subchondral bone. An irregularity of MFC on MRI is correlated with OA disease severity clinically and histopathologically. The new computer software is useful to objectively assess OA disease severity.

Elevated osteopontin level of synovial fluid and articular cartilage is associated with disease severity in knee osteoarthritis patients

To investigate osteopontin (OPN) levels in both synovial fluid and articular cartilage of patients with primary knee osteoarthritis (OA) and their relationship with severity of the disease. Fifty patients aged 48-81 years with knee OA and 10 healthy controls were enrolled in this study. Anteroposterior knee radiographs or/and Mankin score were taken to determine the disease severity of the affected knee. The radiographic grading of OA in the knee was performed by using the Kellgren-Lawrence criteria. OPN levels in synovial fluid were measured using enzyme-linked immunosorbent assay. OPN levels in articular cartilage were assessed by immunohistochemical methods. Compared to healthy controls, OA patients had higher OPN concentration in synovial fluid (4519.60+/-1830.37, 95%CI 3999.42-5039.79 vs 1179.70+/-303.39, 95%CI 1035.53-1438.74 pg/ml, P<0.001)and articular cartilage(0.6+/-0.06, 95%CI 0.59-0.62 vs 0.43+/-0.07, 95%CI 0.38-0.48, P<0.01). In addition, synovial fluid OPN levels showed a positive correlation with articular cartilage OPN levels (r=0.411, 95%CI 0.150-0.619, P=0.003). Subsequent analysis showed that synovial fluid OPN levels significantly correlated with severity of disease (Spearman's rho=0.581, 95%CI 0.335-0.726, P<0.001). Furthermore, the articular cartilage levels of OPN also correlated with disease severity (Spearman's rho=0.675, 95%CI 0.500-0.808, P<0.001). OPN in synovial fluid and articular cartilage is associated with progressive joint damage and is likely to be a useful biomarker for determining disease severity and progression in knee OA.

Relationship of plasma and synovial fluid BMP-7 with disease severity in knee osteoarthritis patients: a pilot study

The objective of this study was to investigate bone morphogenetic protein-7 (BMP-7) levels in both plasma and synovial fluid of patients with primary knee osteoarthritis (OA) and to determine their relationship to disease severity. Thirty-two patients with knee OA and 15 healthy subjects were enrolled in the study. Anteroposterior knee radiographs were taken to determine the disease severity of the affected knee. The radiographic grading of OA in the knee was performed using the Kellgren-Lawrence criteria. BMP-7 levels in the plasma and synovial fluid were measured using enzyme-linked immunosorbent assay. The mean plasma BMP-7 concentration of the knee OA patients was significantly higher compared with that of healthy controls (12.1 +/- 1.6 vs 3.5 +/- 0.9 pg/ml, P = 0.001). Although BMP-7 levels in plasma were higher with respect to paired synovial fluid samples, the difference was not statistically significant (12.1 +/- 1.6 vs 10.5 +/- 2.2 pg/ml, P = 0.3). Subsequent analysis showed that plasma BMP-7 levels significantly correlated with disease severity (r = 0.77, P < 0.001). Furthermore, the synovial fluid levels of BMP-7 also correlated with disease severity (r = 0.60, P < 0.001). In addition, plasma BMP-7 levels showed a positive correlation with synovial fluid BMP-7 levels (r = 0.71, P < 0.001). Overexpression of BMP-7 in plasma and synovial fluid is related to progressive joint damage in knee OA. These findings suggest that BMP-7 might serve as a biochemical parameter for determining disease severity in primary knee OA and could play a potential role in cartilage protection and repair of OA.

Biomechanical changes at the hip, knee, and ankle joints during gait are associated with knee osteoarthritis severity

Mechanical factors have been implicated in the progression of knee osteoarthritis (OA). Understanding how these factors change as the condition progresses would elucidate their role and help in developing interventions that could delay the progress of knee OA. In this cross-sectional study, we identified kinematic and kinetic variables at the hip, knee, and ankle joints that change between three clinically distinct levels of knee OA disease severity: asymptomatic, moderate OA, and severe OA. The severity level was based on a combined radiographic/symptomatic clinical decision for treatment with (severe) or without (moderate) total knee replacement surgery. Gait variables that changed between groups were categorized as: those that differed between the asymptomatic group and both OA groups, those that differed between the asymptomatic group and the severe OA group only, or those that changed progressively, that is, the asymptomatic differed from the moderate OA, and the moderate OA differed from the severe OA group. Changes seen in both OA subject groups compared to asymptomatic included increased mid-stance knee adduction moments, decreased peak knee flexion moments, decreased peak hip adduction moments, and decreased peak hip extension moments. Changes found only in the severe knee OA group included multiple kinematic and kinetic differences at the hip, knee, and ankle joints. Gait differences that progressed with OA severity included decreased stance phase knee flexion angles, decreased early stance knee extension moments, decreased peak stance phase hip internal rotation moments, and decreased peak ankle dorsiflexion moments.

Angiogenesis in the synovium and at the osteochondral junction in osteoarthritis

We hypothesised that osteochondral and synovial angiogenesis in osteoarthritis (OA) are independent processes. We investigated whether indices of osteochondral and synovial angiogenesis display different relationships with synovitis, disease severity and chondrocalcinosis in patients with OA. Synovium and medial tibial plateaux were obtained from 62 patients undergoing total knee joint replacement for OA (18 [29%] had chondrocalcinosis) and from 31 recently deceased people with no evidence of joint pathology post-mortem (PM). Vascular endothelium, proliferating endothelial cells (ECs) and macrophages were quantified by immunohistochemistry for CD34, CD31/Ki67 and CD14, respectively. Grades were assigned for radiographic and histological OA disease severity, clinical disease activity and histological synovitis (based on cellular content of the synovium). Blood vessels breached the tidemark in 60% of patients with OA and 20% of PM controls. Osteochondral vascular density increased with increasing cartilage severity and clinical disease activity scores, but not with synovitis. Synovial EC proliferation, inflammation and macrophage infiltration were higher in OA than in PM controls. Synovial angiogenesis indices increased with increasing histological synovitis, but were not related to osteochondral vascular density or other indices of OA disease severity. OA changes were more severe in patients with concurrent chondrocalcinosis. Chondrocalcinosis was not associated with increased angiogenesis or histological synovitis beyond that seen in OA alone. Osteochondral and synovial angiogenesis appear to be independent processes. Osteochondral vascularity is associated with the severity of OA cartilage changes and clinical disease activity, whereas synovial angiogenesis is associated with histological synovitis. Modulation of osteochondral and synovial angiogenesis may differentially affect OA disease.

Chondrocyte gene expression in osteoarthritis: Correlation with disease severity

Osteoarthritis is characterized by a progressive degradation of cartilage structure and function. This study tests the hypothesis that disease severity is characterized by alterations in expression of cartilage-specific genes for aggrecan and collagen type II. Cartilage, discarded from six subjects undergoing knee replacement, was subdivided into homogeneous portions by the surgeon according to the Outerbridge classification. For four subjects, it was possible to separate the tissue into two or three fractions with different disease severity. Portions of each sample were prepared either for histological analysis and ranking according to the Mankin system or for RNA extraction. Quantitative, competitive RT-PCR assays were used for measurement of mRNA for aggrecan, collagen type II, and glyceraldehyde-3-phosphate dehydrogenase. Clinical grading was correlated with histological score (Spearman r = 0.60, p = 0.043). There was a striking decrease in expression of aggrecan and collagen II that was correlated with increase in the grade in regions of cartilage within an individual subject. In the series of 12 samples, there was an inverse correlation between aggrecan expression and osteoarthritis grade (Spearman r = -0.59, p = 0.042). In conclusion, there was an inverse relationship between regional disease severity in osteoarthritis and expression of aggrecan. Use of quantitative, competitive RT-PCR is practical for assessment of chondrocyte gene signatures.

The clinical correlates of articular cartilage defects in symptomatic knee osteoarthritis: a prospective study

To determine whether articular cartilage defects are associated with cartilage loss and joint replacement in subjects with symptomatic knee osteoarthritis (OA). One hundred and seventeen subjects with symptomatic knee OA underwent magnetic resonance imaging of their dominant knee at baseline and 2 yr later. Cartilage defects were identified as prevalent (defect score > or =2) in each knee compartment. Occurrence of joint replacement by 4 yr was documented. Cartilage defects were present in 81% of medial, 64% of lateral tibiofemoral compartments and 55% of patellar cartilages. Annual patellar cartilage loss was highest in those with defects compared with no defects (5.5% vs 3.2%, P = 0.01). Tibial cartilage loss was not associated with defects in the medial (4.6% vs 5.8%, P = 0.42) or lateral (4.7% vs 6.5%, P = 0.21) tibial cartilages. Higher total cartilage defect scores (8-15) were associated with a 6.0-fold increased risk of joint replacement over 4 yr compared with those with lower scores (2-7) (95% confidence interval 1.6, 22.3), independently of potential confounders. Articular cartilage defects are associated with disease severity in knee OA and predict patellar cartilage loss and knee replacement.

Serum cartilage oligomeric matrix protein reflects osteoarthritis presence and severity: the Johnston County Osteoarthritis Project.

To characterize serum cartilage oligomeric matrix protein (COMP) levels by age and gender for a radiographically defined population free of hip and knee osteoarthritis (OA), and to examine the potential utility of COMP as a diagnostic biomarker for knee OA. Serum samples and knee and hip radiographs were obtained at a baseline evaluation as part of the Johnston County Osteoarthritis Project, a population-based study of OA in rural North Carolina. A total of 291 Caucasian participants were randomly selected for COMP analysis, 143 patients with radiographic knee OA (Kellgren/Lawrence [K/L] grade > or = 2) and 148 controls with neither hip nor knee OA (K/L grade 0), evenly distributed by age and gender. COMP was quantified by competitive enzyme-linked immunosorbent assay with monoclonal antibody 17-C10. The natural log-transformed COMP data were analyzed using general linear models. Serum COMP levels were significantly elevated (P = 0.0001) in the age > or = 65 group (mean +/- SD 1,302.1 +/- 496.7 ng/ml) versus the age 45-54 and age 55-64 groups (1,058.1 +/- 432.4 and 1,038.6 +/- 313.3, respectively). Serum COMP levels of the OA group were significantly higher than those of the control group (1,208.57 +/- 487.47 ng/ml versus 1,061.83 +/- 370.58 ng/ml; P = 0.0093). Serum COMP levels also increased significantly with knee OA K/L grade (P = 0.0047), knee OA laterality (P = 0.0043), and number of knee and hip joints involved (P = 0.0001). There was no significant difference in serum COMP levels by gender or obesity. We demonstrate that in a population-based sample, serum COMP levels can distinguish an OA-affected subgroup from an unaffected subgroup and can reflect disease severity and multiple joint involvement in OA.

Knee adduction moment, serum hyaluronan level, and disease severity in medial tibiofemoral osteoarthritis.

The adduction moment at the knee during gait is the primary determinant of medial-to-lateral load distribution. If the adduction moment contributes to progression of osteoarthritis (OA), then patients with advanced medial tibiofemoral OA should have higher adduction moments. The present study was undertaken to investigate the hypothesis that the adduction moment normalized for weight and height is associated with medial tibiofemoral OA disease severity after controlling for age, sex, and pain level, and to examine the correlation of serum hyaluronan (HA) level with disease severity and with the adduction moment in a subset of patients. Fifty-four patients with medial tibiofemoral OA underwent gait analysis and radiographic evaluation. Disease severity was assessed using the Kellgren-Lawrence (K-L) grade and medial joint space width. In a subset of 23 patients with available sera, HA was quantified by sandwich enzyme-linked immunosorbent assay. Pearson correlations, a random effects model, and multivariate regression models were used. The adduction moment correlated with the K-L grade in the left and right knees (r = 0.68 and r = 0.60, respectively), and with joint space width in the left and right knees (r = -0.45 and r = -0.47, respectively). The relationship persisted after controlling for age, sex, and severity of pain. The partial correlation between K-L grade and adduction moment was 0.71 in the left knees and 0.61 in the right knees. For every 1.0-unit increase in adduction moment, there was a 0.63-mm decrease in joint space width. In the subset of patients in whom serum HA levels were measured, HA levels correlated with medial joint space width (r = -0.55), but not with the adduction moment. There is a significant relationship between the adduction moment and OA disease severity. Serum HA levels correlate with joint space width but not with the adduction moment. Longitudinal studies will be necessary to determine the contribution of the adduction moment, and its contribution in conjunction with metabolic markers, to progression of medial tibiofemoral OA.