Disease Severity In Osteoarthritis Research Articles

Adiponectin: is it a biomarker for assessing the disease severity in knee osteoarthritis patients?

The results of previous studies regarding the role of adiponectin in the pathogenesis of osteoarthritis (OA) are controversial. The aim of this study is to investigate the relation of plasma adiponectin levels with clinical and radiological disease severity in knee OA patients. Sixty patients with knee OA and 25 healthy controls were included in the study. Patients were divided into two subgroups: lean (Group 1, n = 30) and obese (Group 2, n = 30). Healthy controls were accepted as Group 3 (n = 25). Pain intensity was measured with a visual analogue scale (VAS), functional disability with Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Quality of Life (QoL) with Short Form-36 (SF-36). Also all patients were radiologically evaluated and graded according to Kellgren-Lawrence (KL) scale. Plasma concentrations of adiponectin levels were measured by enzyme-linked immune-sorbent assay (ELISA). Serum adiponectin levels were higher in OA patient subgroups than those in the control group but the difference did not reach a significant level after adjustments for age, gender and body mass index (P = 0.078). There was a positive correlation between adiponectin concentration and KL grading scores. Additionally, there was a positive correlation between adiponectin levels and clinical variables (VAS and WOMAC total scores) in patient subgroups (r = 0.326 P = 0.012, r = 0.583 P < 0.001, respectively). SF-36 scores were inversely associated with adiponectin levels. Plasma adiponectin concentrations were associated with both clinical and radiological disease severity in knee OA patients. Thus, adiponectin hormone might be a potential clinically useful biomarker while assessing disease severity in the future.

Possible Involvement of Serum and Synovial Fluid Resistin in Knee Osteoarthritis: Cartilage Damage, Clinical, and Radiological Links.

Resistin is an adipocytokine associated with inflammation and insulin resistance. Recent studies have shown that resistin plays an important role in the pathogenesis and progression in osteoarthritis (OA) patients. The current study was aimed at investigating the relationship between resistin in serum and synovial fluid (SF) and disease severity in patients with knee osteoarthritis. Seventy-four patients diagnosed with knee OA and 79 healthy controls receiving regular body check in our hospital were recruited in the study. The Noyes score method was used to assess articular cartilage damage arthroscopically. The symptomatic severity was evaluated according to the Western Ontario McMaster University Osteoarthritis (WOMAC) scores. The radiographic disease severity of OA was assessed by the Kellgren-Lawrence (K-L) grading system. The resistin levels in serum and SF were determined by enzyme-linked immunosorbent assay. Cartilage degradation marker CTX-II in SF was also examined. SF but not serum resistin levels are positively associated with Noyes scores, K-L grading scores WOMAC pain scores, physical functional scores and WOMAC total scores. In addition, SF resistin correlated positively with CTX-II. Resistin in SF might serve as a potential biomarker for reflecting the disease severity and cartilage degenerative extent of knee OA.

New insight in the relationship between regional patterns of knee cartilage thickness, osteoarthritis disease severity, and gait mechanics

To test if the relationship between knee kinetics during walking and regional patterns of cartilage thickness is influenced by disease severity we tested the following hypotheses in a cross-sectional study of medial compartment osteoarthritis (OA) subjects: (1) the peak knee flexion (KFM) and adduction moments (KAM) during walking are associated with regional cartilage thickness and medial-to-lateral cartilage thickness ratios, and (2) the associations between knee moments and cartilage thickness data are dependent on disease severity. Seventy individuals with medial compartment knee OA were studied. Gait analysis was used to determine the knee moments and cartilage thickness was measured from magnetic resonance imaging. Multiple linear regression analyses tested for associations between cartilage thickness and knee kinetics. Medial cartilage thickness and medial-to-lateral cartilage thickness ratios were lower in subjects with greater KAM for specific regions of the femoral condyle and tibial plateau with no associations for KFM in patients of all disease severities. When separated by severity, the association between KAM and cartilage thickness was found only in patients with more severe OA, and KFM was significantly associated with cartilage thickness only for the less severe OA subjects for specific tibial plateau regions. The results support the idea that the KAM is larger in patients with more severe disease and the KFM has greater influence early in the disease process, which may lessen as pain increases with disease severity. Each component influences different regions of cartilage. Thus the relative contributions of both KAM and KFM should be considered when evaluating gait mechanics and the influence of any intervention for knee OA.

Influence of osteoarthritis grade on molecular signature of human cartilage.

Articular chondrocytes maintain cartilage matrix turnover and have the capacity for anabolic and catabolic activities that can be influenced by injury and disease. This study tested the hypothesis that catabolic genes are upregulated with regional osteoarthritis (OA) disease severity within a joint. With IRB approval, specimens of knee cartilage obtained as discarded tissues from subjects undergoing arthroplasty were partitioned for each subject by OA disease severity and evaluated for gene expression by RT-PCR. There was regional OA grade-associated upregulation of expected inflammatory mediators TNF-α, TNF receptors, IFN-γ, and interleukins as well as genes encoding proteolytic enzymes, including Adamts-5 and MMPs. Osteoclast-related genes, cathepsin K, tartrate-resistant acid phosphatase (TRAP), RANKL, RANK, M-CSF, and c-fms, but not osteoprotegerin, were induced in advanced grades. In vitro treatment of normal human chondrocytes with interleukin-1β upregulated similar genes; this provides evidence that chondrocytes per se can be the source of osteoclast-related factors. Immunohistochemical staining showed that RANK- and RANKL-positive cells were abundant in advanced grades, especially in chondrocyte clusters. This suggests a possible autocrine mechanism by which an osteoclast phenotype is induced in articular chondrocytes. In sum, these studies identified gene expression signatures in human OA cartilage based upon regional disease severity within a joint. There was an effect of OA Grade on expression of osteoclastic lytic enzymes and regulatory factors in human articular chondrocytes. Induction of an osteoclast-like phenotype in chondrocytes may be part of OA progression and suggests specific therapeutic approaches.

Correlation of bone morphogenetic protein-2 levels in serum and synovial fluid with disease severity of knee osteoarthritis.

BackgroundThis study aimed to investigate the bone morphogenetic protein-2 (BMP-2) levels in serum and synovial fluid (SF) of patients with primary knee osteoarthritis (OA) and to exam its correlation with radiographic and symptomatic severity of the disease.Material/MethodsA total of 37 knee OA patients and 20 healthy controls were enrolled in this study. Knee OA radiographic grading was performed according to the Kellgren-Lawrence (KL) grading system by evaluating X-ray changes observed in anteroposterior knee radiography. Symptomatic severity of the disease was evaluated according to the Western Ontario McMaster University Osteoarthritis Index (WOMAC) scores. BMP-2 levels in serum and SF were determined using enzyme-linked immunosorbent assay.ResultsSerum BMP-2 level in patients with knee OA was higher than that in healthy controls. Knee OA patients with KL grade 4 showed significantly elevated BMP-2 levels in the serum and SF compared with those with KL grade 2 and 3. Knee OA patients with KL grade 3 had significant higher SF levels of BMP-2 than those with KL grade 2. BMP-2 levels in the serum and SF of knee OA patients were both positively correlated with KL grades and WOMAC scores.ConclusionsBMP2 levels in serum and SF were closely related to the radiographic and symptomatic severity of knee OA and may serve as an alternative biochemical parameter to determine disease severity of primary knee OA.

Plasma and synovial osteopontin levels, are they associated with disease severity of primary knee osteoarthritis in Egyptian patients?

Aim of the workThe aim of this study was to examine osteopontin (OPN) levels in both plasma and synovial fluid of patients with primary knee osteoarthritis (OA) and to investigate their relationship with severity of the disease. Patients and methodsFifty patients with primary knee OA were compared to twenty-five apparently healthy controls. OPN levels in plasma and synovial fluid were measured using enzyme-linked immunosorbent assay. Severity of knee pain was assessed by the Western Ontario and McMaster Universities osteoarthritis index. Radiographic grading of knee OA was performed by Kellgren–Lawrence criteria. Magnetic resonance imaging (MRI) was also performed on painful knees. ResultsPlasma OPN was higher in patients (159.65±28.56ng/ml) than controls (90.45±23.63ng/ml). OPN in plasma and synovial fluid was correlated with severity of knee pain (r=0.878, r=0.795, P<0.001). Cartilage loss, marginal osteophytes and subchondral bone cyst were the commonest MRI findings in knee OA. MRI detected also patients with early knee OA that were not detected by plain radiography. ConclusionOPN serves as a biochemical marker of disease severity in knee OA. It also could be predictive to the progression of disease.

Plasma and synovial fluid sclerostin are inversely associated with radiographic severity of knee osteoarthritis

ObjectiveThe purpose of this study was to analyze sclerostin in plasma and synovial fluid of knee osteoarthritis (OA) patients and to investigate the association between sclerostin levels and radiographic severity. Design and methodsA total of 190 subjects (95 knee OA patients and 95 healthy controls) were recruited in the present study. Sclerostin levels in plasma and synovial fluid were assessed using an enzyme-linked immunosorbent assay. OA grading was performed using the Kellgren–Lawrence classification. ResultsPlasma sclerostin levels were significantly lower in OA patients than in healthy controls (P=0.004). Additionally, sclerostin levels in plasma were significantly higher with respect to paired synovial fluid (P<0.001). Moreover, sclerostin levels in plasma and synovial fluid demonstrated a significant inverse correlation with the radiographic severity of knee OA (r=−0.464, P<0.001 and r=−0.592, P<0.001, respectively). Subsequent analysis revealed that there was a positive correlation between plasma and synovial sclerostin levels (r=0.657, P<0.001). ConclusionsSclerostin was significantly lower in OA plasma samples when compared with healthy controls. Plasma and synovial fluid sclerostin levels were inversely associated with the radiographic severity of knee OA. Therefore, sclerostin may be utilized as a biochemical marker for reflecting disease severity in primary knee OA.

Extending the use of PROMs in the NHS—using the Oxford Knee Score in patients undergoing non-operative management for knee osteoarthritis: a validation study

ObjectivesTo assess the validity of the Oxford Knee Score (OKS) for use in patients undergoing non-operative management for their knee osteoarthritis (OA) within the National Health Service (NHS).DesignObservational cohort study.SettingSingle...

SAT0347 Cartilaginous Uric Acid Deposition in Advanced Osteoarthritis: Innocent Bystander or Promotor of Cartilage Destruction?

ObjectivesRecent studies have suggested that synovial fluid uric acid could contribute to tissue inflammation, disease severity and progression of osteoarthritis (OA). Intraarticular uric acid has been associated with OA disease...

Usefulness of specific OA biomarkers, thrombin-cleaved osteopontin, in the posterior cruciate ligament OA rabbit model

We undertook this study to determine whether thrombin-cleaved osteopontin (OPN) in synovial fluid (SF) represents a useful marker of osteoarthritis (OA) progression in the posterior cruciate ligament transection (PCLT) OA rabbit model. PCLT was performed on the right knee joints of 48 rabbits. The rabbits were then sacrificed separately at 4, 8, 16, and 24 weeks post-surgery, when the joint was harvested and macroscopic and histological assessments of articular cartilage were performed. Thrombin-cleaved OPN product in SF was determined using Western blotting and the levels were measured using an enzyme-linked immunoassay. The macroscopic and histological scores for PCLT knees were already elevated 4 weeks after surgery and increased with time. Western blotting showed the presence of thrombin-cleaved OPN in SF from PCLT knees. Thrombin-cleaved OPN levels in SF were elevated at 4 weeks (P < 0.001) and were elevated peaking at 24 weeks (P < 0.00001) after PCLT compared to baseline. A positive significant correlation was found between thrombin-cleaved OPN levels and the macroscopic scores (8 weeks: ρ = 0.695, P = 0.012; 16 weeks: ρ = 0.751, P = 0.005; 24 weeks: ρ = 0.660, P = 0.020). Furthermore, the same correlation was noted between thrombin-cleaved OPN levels and the histological scores (4 weeks: ρ = 0.609, P = 0.036; 8 weeks: ρ = 0.662, P = 0.019; 16 weeks: ρ = 0.827, P = 0.001; 24 weeks: ρ = 0.813, P = 0.001). In this rabbit model of PCLT, thrombin-cleaved OPN levels in SF appear to provide a useful marker of OA disease severity and progression.

Synovial Fluid Omentin-1 Levels Are Inversely Correlated With Radiographic Severity of Knee Osteoarthritis

ObjectiveThe purpose of this study was to demonstrate omentin-1 levels in serum and synovial fluid (SF) of patients with knee osteoarthritis (OA) and to investigate their correlation with radiographic disease...

Soluble lectin-like oxidized low-density lipoprotein receptor-1 levels in synovial fluid are correlated with disease severity of knee osteoarthritis

ObjectivesThis study was aimed to measure soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1) levels in serum and synovial fluid (SF) of knee osteoarthritis (OA) patients and to investigate the correlation between sLOX-1 levels and the disease severity. Design and methodsTwo hundred and sixteen OA patients and 83 healthy controls were enrolled in this study. All OA patients were scored for Kellgren–Lawrence (KL) grade (0–4). The sLOX-1 levels were measured by enzyme-linked immunosorbent assay (ELISA). ResultsIn OA patients, the mean sLOX-1 levels in SF were markedly lower than those in paired serum samples (P<0.01). The SF sLOX-1 levels increased with higher KL grade (P<0.01) and were significantly correlated with disease severity (r=0.324, P<0.01). SF sLOX-1 level was the independent factor for predicting the disease severity of OA (β: 0.281, 95%CI: 0.145–0.396). ConclusionsSF sLOX-1 levels were independently and positively associated with disease severity in knee OA.

Correlation of synovial fluid and articular cartilage osteopontin with disease severity in knee osteoarthritis

Objective To examine osteopontin (OPN) levels in both synovial fluid and articular cartilage of patients with primary knee osteoarthritis (OA) and to investigate their relationship with severity of the disease. Methods Fifty patients with knee OA and 10 healthy controls were enrolled in this study.There were 15 males and 35 females with an average age of 61.8±7.4 years in OA group. The control group included 4 males and 6 females with an average age of 63.2±6.0 years. Mankin score 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. OPN levels in synovial fluid were measured using enzyme-linked immunosorbent assay. OPN levels in articular cartilage were assessed by immunohistochemical methods. Results Compared to healthy controls, the knee OA patients had higher OPN concentration in synovial fluid ([4519.60±1830.37] pg/ml vs. [1179.70±303.39] pg/ml) and articular cartilage([0.60±0.06] vs. [0.43 ±0.07]). In addition, synovial fluid OPN levels showed a positive correlation with articular cartilage OPN levels (r=0.411,P=0.003). Subsequent analysis showed that the OPN levels in synovial fluid significantly had been correlated with severity of disease using Kellgren-Lawrence criteria (r=0.581, P＜ 0.001). Furthermore,the levels of OPN in the articular cartilage also were correlated with disease severity using Mankin score (r=0.675, P＜ 0.001).Conclusion The data suggest that OPN in synovial fluid and articular cartilage is related to progressive joint damage and could be a predictive biomarker respect to disease severity and progression in knee OA. Key words: Osteopontin; Osteoarthritis, knee; Synovial fluid; Cartilage, articular

The nerve of osteoarthritis pain

Cumulative data suggest that central sensitization may contribute to pain in osteoarthritis (OA) and present with symptoms typically associated with neuropathic pain (NP). We evaluated the responses from focus group participants on the knee OA pain experience for pain descriptions that suggest NP. Focus group transcripts were analyzed by 2 independent assessors for unprompted use of pain descriptors that suggested NP. Items from validated NP symptom-based questionnaires were used to guide the analysis. Data on sociodemographic factors, duration of knee OA, and OA disease and pain severity (using the Western Ontario and McMaster Universities Osteoarthritis Index and a numerical rating scale) were obtained from questionnaires administered after focus group completion. These factors were compared among participants who did and did not use descriptors that suggested NP. Transcripts from 80 knee OA participants were analyzed. A range of NP descriptors was used to characterize their knee symptoms, including burning, tingling, numbness, and pins and needles. The proportion of participants who used NP descriptors was 0.34 (95% confidence interval 0.24-0.45). Those who used NP descriptors were younger (P = 0.003) and, although not statistically different, more likely to be women, with higher pain intensity and OA severity and longer OA duration, than those who did not use NP descriptors. During focus groups, a subset of adults with chronic, symptomatic knee OA used pain quality descriptors that were suggestive of NP. Elicitation of NP descriptors in people with OA may help identify those who could benefit from further evaluation and perhaps treatment for NP.

Relationship of disease severity in osteoarthritis with pain, function, and work productivity

A number of medications are approved in the United States (US) for treatment of moderate-to-severe pain. Clinical trial definitions of moderate-to-severe pain in osteoarthritis (OA) are generally based on scoring cut-points for patient-reported pain, physical function, and global assessments. However, in real world settings, categorizing patients as having mild, moderate, or severe OA is not straightforward. The objective of this study was to assess patient-reported OA severity in terms of patient function using the Adelphi Disease Specific Programme for Arthritis (OA DSP VII, 2008).

Health status and disease severity in osteoarthritis

Health status and disease severity in osteoarthritis

Relationship between patient-reported disease severity in osteoarthritis and self-reported pain, function and work productivity

IntroductionUnderstanding the relationship between patient-reported osteoarthritis (OA) severity and other patient-reported outcomes in the real-world clinical setting can provide a basis for appropriate patient management. The objective of this study was to determine how patient-reported OA severity correlates with patient-reported outcomes including pain, function and productivity.MethodsWe used the Adelphi Disease Specific Programme (DSP) for OA, a database aggregated from large, multinational, observational studies for specific chronic diseases. Data were obtained based on a 0 to 100 mm pain visual analogue scale (VAS) and a series of questions including functioning (that is, activities of daily living) and work productivity. OA severity was rated by the patients based on the question "How bad would you say your arthritis is now?" with potential responses of "mild," "moderate," and "severe." Regression models and chi-square analyses were used to evaluate the relationships between self-reported OA severity and other outcomes.ResultsOf 998 subjects in the OA DSP U.S. database, 714 (72.5%) agreed to participate. This sample was predominantly female (61.7%) with a mean age of 63.8 ± 12.9 years. Increased OA severity was associated with an older population (P < 0.05). With increasing OA severity (mild, moderate, severe), statistically significant differences (P < 0.05) were observed in increased pain VAS scores (23.5, 50.2, 70.8, respectively), lower functioning outcomes, and a higher percent of overall work impairment due to OA (17%, 37%, 48%, respectively). The increased work impairment at greater severity levels also resulted in higher costs related to lost work productivity, with annual costs due to lost productivity estimated at $6,096, $13,2510, and $17,214 per patient for self-reported mild, moderate, and severe OA, respectively (P < 0.05 for pairwise comparisons).ConclusionsIn the clinical practice setting, patient-reported OA severity was associated with other key patient-reported outcomes and thus may provide an accurate and tangible assessment of patients' perceptions of their disease. Identifying OA patients by their perceived severity level may be of benefit to patients and health-care providers when choosing treatment options aimed at reducing pain, and improving function and productivity.

Correlation of pain relief with physical function in hand osteoarthritis: randomized controlled trial post hoc analysis

IntroductionNonsteroidal anti-inflammatory drugs are recommended for the relief of pain associated with hand osteoarthritis (OA) but do not alter the underlying structural changes that contribute to impaired physical function. The current analysis examined the relationship of pain relief with measures of function and global rating of disease in patients with hand OA.MethodsThis was a combined analysis of 2 prospective, randomized, double-blind, 8-week, multicenter, parallel-group studies comparing diclofenac sodium 1% gel with placebo gel (vehicle) in patients with radiographically confirmed mild to moderate hand OA. Patients (n = 783) aged ≥ 40 years applied diclofenac sodium 1% gel (2 g) or vehicle to each hand 4 times daily for 8 weeks. Outcome measures included pain intensity assessed on a 100-mm Visual Analog Scale (VAS); the Australian/Canadian Osteoarthritis Hand Index (AUSCAN) subscales for pain, stiffness, and physical function (100-mm VAS); and a global rating of disease (100-mm VAS). Change in VAS pain intensity from baseline to week 8 was categorized (<0%, 0%-<15%, 15%-<30%, 30%-<50%, 50%-<70%, and ≥ 70%) without regard to treatment and compared in each category with the mean change from baseline in each AUSCAN subindex and the global rating of disease. Pearson correlations between changes in outcome measures from baseline to week 8 were calculated.ResultsChanges in VAS pain intensity were accompanied by similar changes in AUSCAN scores and global rating of disease. Pearson correlations confirmed significant associations (P < 0.001) between change in VAS pain intensity and changes in AUSCAN pain (correlation coefficient [r] = 0.81), AUSCAN function (r = 0.75), AUSCAN stiffness (r = 0.66), and global rating of disease (r = 0.76).ConclusionsPain relief correlated with improvements in physical function, stiffness, and global rating of disease in patients with hand OA, irrespective of treatment. This suggests that pain or anticipation of pain inhibits physical function and influences patient perception of disease severity in hand OA. These results also suggest that any intervention to relieve the pain of hand OA may improve function and patient perception of disease severity, despite the absence of a disease-modifying mechanism of action.Trial registrationClinicaltrials.gov NCT00171652, NCT00171665.

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.