Radiographic Severity Of Knee Osteoarthritis Research Articles

Radiographic knee osteoarthritis severity has no impact on fall risk: the locomotive syndrome and health outcomes in the aizu cohort study (LOHAS): a cross-sectional study

BackgroundTo investigate factors that have an impact on the risk of falls and determine whether radiographic knee osteoarthritis (KOA) is a factor involved in falls independent of knee pain, psychological factors, and physical function.MethodsA cross-sectional analysis was conducted on 1083 subjects for the 2009 Locomotive Syndrome and Health Outcomes in the Aizu Cohort Study (LOHAS). A logistic regression analysis was performed to examine the relationship between radiographic KOA and fall history.ResultsFall history was significantly associated with the severity of knee pain. Compared to subjects with no knee pain, the odds ratio (OR) was 1.53 times higher in the subjects with mild knee pain (95% confidence interval [CI]: 1.04–2.25), 1.69 times higher in those with moderate knee pain (95%CI: 1.03–2.79), and 2.98 times higher in those with severe knee pain (95%CI: 1.67–5.30). In subjects with depression, the OR was 1.91 (95%CI: 1.25–2.92), and in those with decreased mobility, the OR was 1.70 (95%CI: 1.08–2.69). Age, gender, knee crepitus, BMI, OLST, and sleeping pill use were not significantly associated with fall risk. In a multivariate analysis, radiographic KOA severity was not significantly associated with fall risk (OR 0.81, 95%CI 0.44–1.50 in mild OA; OR 1.10, 95%CI 0.57–2.14 in severe OA).ConclusionKnee pain, decreased mobility, and depression, but not the radiographic KOA severity, were significantly associated with a fall risk. Regardless of the individual's radiographic KOA severity, the risk of falls may be reduced by treating his/her knee pain, mobility problems, and/or psychological factors.

Predicting the onset of end-stage knee osteoarthritis over two- and five-years using machine learning

ObjectiveIdentifying participants who will progress to advanced stage in knee osteoarthritis (KOA) trials remains a significant challenge. Current tools, relying on total knee replacements (TKR), fall short in reliability due to the extraneous factors influencing TKR decisions. Acknowledging these limitations, our study identifies a critical need for a more robust metric to assess severe KOA. The end-stage KOA (esKOA) measure, which combines symptomatic and radiographic criteria, serves as a solid indicator. To enhance future trials that use esKOA as an endpoint, our study focuses on developing and validating a machine-learning tool to identify individuals likely to develop esKOA within 2 to 5 years. DesignUtilizing the Osteoarthritis Initiative (OAI) data, we trained models on 3,114 participants and validated them with 606 participants for the right knee, and similarly for the left knee, with external validation from the Multicentre Osteoarthritis Study (MOST) involving 1,602 participants. We aimed to predict esKOA onset at 2-to-2.5 years and 4-to-5 years, defining esKOA by severe radiographic KOA with moderate/severe symptoms or mild/moderate radiographic KOA with persistent/intense symptoms. Our analysis considered 51 candidate predictors, including demographics, clinical history, physical examination, and X-ray evaluations. An online tool predicting esKOA progression, based on models with ten and nine predictors for the right and left knees, respectively, was developed. ResultsExternal validation (MOST) for the right knee at 2.5 years yielded an Area Under Curve (AUC) of 0.847 (95 % CI 0.811 to 0.882), and at 5 years, 0.853 (95 % CI 0.823 to 0.881); for the left knee at 2.5 years, AUC was 0.824 (95 % CI 0.782 to 0.857), and at 5 years, 0.807 (95 % CI 0.768 to 0.843). Models with fewer predictors demonstrated comparable performance. The online tool is available at: https://eskoa.shinyapps.io/webapp/. ConclusionOur study unveils a robust, externally validated machine learning tool proficient in predicting the onset of esKOA over the next 2 to 5 years. Our tool can lead to more efficient KOA trials.

Higher fibular head is a risk for lateral hinge fracture in medial open wedge high tibial osteotomy.

To examine the association between the hinge position, fibular head position, and type III lateral hinge fracture (LHF) in patients with knee osteoarthritis (OA) who underwent medial open wedge high tibial osteotomy (MOWHTO). This retrospective study examined patients who underwent MOWHTO. Radiographically, the Kellgren-Lawrence (K/L) classification, distance between the articular surface and the tip of the fibular head (fibular head position), hinge point (hinge position), type of LHF, and safe zone (within the proximal tibiofibular joint) outlier were evaluated. To determine the cut-off value of the hinge position and fibular head position associated with type III LHF, a receiver operating characteristic (ROC) curve analysis was performed. The odds ratio (OR) was calculated from the obtained cut-off values using logistic regression, which was adjusted by age, gender, body mass index, and opening distance. Among 132 knees in 120 patients, the radiographic severity of knee OA was 19 (14%), 73 (55%), and 40 (30%) of K/L grades 2, 3, and 4, respectively. LHF was observed in 40 knees (30%), including types I, II, and III fractures in 21 (16%), 5 (4%), and 14 (11%) knees, respectively. Hinge and fibular head positions were 16 and 10mm, respectively, with significant correlation. Safe zone outlier was observed in 38 knees (29%). The hinge and fibular head positions with type III LHF were significantly higher (more cranial) than those with no fracture or other LHF subtypes. The ROC curve revealed that the cut-off value for the hinge and fibular head positions was 13.3 and 8.6mm, respectively. The OR of the hinge and fibular head positions was 22.42 and 13.86, respectively. A higher hinge position was a risk factor for type III LHF and was associated with a higher fibular head in patients with knee OA who underwent MOWHTO. The hinge position should be placed at a certain distance from the articular surface to avoid type III LHF, especially in participants with higher fibular head position, even if the hinge position is located in the safe zone. Retrospective cohort study, Level III.

Outcomes after Genicular Artery Embolization Vary According to the Radiographic Severity of Osteoarthritis: Results from a Prospective Single-Center Study

This prospective single-center study compared outcomes after genicular artery embolization (GAE) in people with mild radiographic knee osteoarthritis (OA) (n = 11) versus moderate to severe radiographic knee OA (n = 22). The mild OA group was older and had experienced symptoms for less time (P < .05). All participants underwent complete embolization of neovessels from genicular arteries. The primary outcome was the proportion of responders at 6 months according to predetermined improvements in pain, function, and/or global change. Results indicated that a higher proportion of participants (n = 9, 81.8%) with mild OA fulfilled responder criteria after treatment compared with people with moderate to severe OA (n = 8, 36.4%) (P = .014). Secondary outcomes for pain, quality of life, and global change were also better in the mild OA group (P < .05). No serious adverse events occurred, including the absence of osteonecrosis on magnetic resonance imaging. The study demonstrated that outcomes after GAE varied according to the severity of baseline radiographic OA.

Correlation between Abdominal Obesity and Pain in Knee Osteoarthritis.

Obesity is an independent risk factor for the occurrence of knee osteoarthritis. The influence of abdominal obesity is not well studied. We proposed to determine the relationship between total abdominal obesity, pain, and functional impairment with the severity of radiographic changes in knee osteoarthritis. A cross-sectional study including 92 patients with knee pain was performed. The evaluation of degree of pain in the knee was assessed by the visual analogue scale and the functional impairment by WOMAC and Lequesne indices. Radiographic severity was assessed by Kellgren and Lawrence score (KL score). Mean age of patients was 55.2 years (19-86), with a predominance of women (80.4% of patients). Mean body mass index (BMI) was 30.66 kg/m2 (18.5-49.97). Obesity was found in 53 patients (57.6%). The average waist circumference (WC) was 102.82 (± 15.51) centimeters. Abdominal obesity was found in 80 patients (87%). Patients had a mean visual analogue scale (VAS) of 18 ± 23.24 mm. The average algofunctionnal Lequesne score was 8.95 (0-23), and the WOMAC score was 26.82 (0-69). Fifty percent of patients had stage 3 of OA according to KL score. We found no association between BMI and intensity of knee pain (p = 0.278), but WC was significantly associated with the elevation of VAS (p = 0.008). Physical function was positively correlated with BMI and WC (p = 0.001). Finally, BMI and WC were significantly associated with radiographic severity (grade 1-2 of KL vs. grade 3-4 of KL) (respectively, p = 0.001; p = 0.017). Both obesity and abdominal obesity are independently associated with pain, disability, and radiographic severity of knee osteoarthritis.

Association of Dipeptidylpeptidase 4 (CD26) With Chondrocyte Senescence and Radiographic Progression in Knee Osteoarthritis.

To evaluate the association of dipeptidylpeptidase 4 (DPP-4; also known as CD26) with cellular senescence of human cartilage and progression of knee osteoarthritis (OA). Articular cartilage sections and chondrocytes were acquired from 35 individuals undergoing total knee replacement for OA to evaluate the following: 1) the association between OA severity and established senescence markers (senescence-associated β-galactosidase activity and p16), which was quantified using immunohistochemistry and flow cytometry (n=19 samples); 2) the coexpression of DPP-4 with established senescence markers, which was assessed using flow cytometry; and 3) expression levels of anabolic and catabolic genes, senescence-related genes, and senescence-associated secretory phenotypes in DPP-4+ and DPP-4- cells, which were isolated using fluorescence-activated cell sorting or magnetic-activated cell sorting (n=16 samples). The concentration of soluble DPP-4 was measured in samples of synovial fluid and samples of plasma from the Prediction of Osteoarthritis Progression cohort and then evaluated for association with the severity of radiographic knee OA at baseline (n=65 samples) and the progression of structural radiographic OA (n=57 samples) over a 3-year period. DPP-4 expression was associated with higher senescence-associated β-galactosidase activity, p16 expression, senescence-related gene and catabolic gene (ADAMTS5, MMP13, IL6, and IL8) expression, higher senescence-associated secretory phenotype secretion, and lower anabolic gene (COL2A1 and ACAN) expression in primary chondrocytes. Synovial fluid DPP-4 concentration was associated with radiographic OA progression (odds ratio 105.32; P=0.015), proteases (synovial fluid matrix metalloproteinase 1 and matrix metalloproteinase 3), aggrecan degradation (synovial fluid sulfated glycosaminoglycan), indicators of activated macrophages (synovial fluid CD14 and CD163), and inflammation (synovial fluid interleukin-6). Our study identifies DPP-4 as a key surface marker in senescent chondrocytes and a predictor of radiographic OA progression.

Do imaging findings modify the effect of non-surgical treatment in patients with knee and hip osteoarthritis? A systematic literature review

ObjectivesTo review the available evidence on diagnostic imaging findings in knee and hip osteoarthritis (OA) as treatment effect modifiers in non-surgical OA interventions.MethodsMEDLINE, Embase and The Cochrane Central Register of...

The natural history of end-stage knee osteoarthritis: Data from the osteoarthritis initiative

ObjectiveWe aimed to describe the natural history leading to end-stage knee osteoarthritis (esKOA), focusing on knee symptoms, radiographic severity, and the presence of limited mobility or instability. MethodsWe performed knee-based analyses of Osteoarthritis Initiative data from 7691 knees (4165 participants). We used a validated definition of esKOA that relied on meeting one of two criteria: (1) severe radiographic knee osteoarthritis (Kellgren-Lawrence [KL] grade=4) with moderate-to-intense pain (Likert WOMAC pain+function>11/88) or (2) KL grade<4 with intense or severe pain (WOMAC pain+function>22) and limited mobility (flexion contracture≥5°) or instability (based on a varus and valgus stress test). We also introduced an alternate definition of esKOA that relied on meeting one of two criteria that omitted physical exam findings:(1) severe radiographic knee osteoarthritis (KL grade=4) with at least moderate symptoms or (2) KL grade=2 or 3 with intense or severe symptoms and persistent knee pain (frequent knee pain during three or more months in the past year). We used descriptive statistics to explore the frequency of components of esKOA at the index visit when they had incident esKOA, at the annual visit before developing esKOA, and the interval change between those visits. ResultsOur analytic sample was mostly female (58%), without radiographic knee osteoarthritis (KL grade=0 or 1; 60%), without stability or mobility concerns (91%), and without persistent knee pain (77%). At the visit before incident esKOA, most knees already had moderate-to-severe radiographic osteoarthritis using the original (62%) or alternate (50%) definition (versus <15% for either definition of no esKOA). Over 80% of knees that reached the criteria for esKOA achieved this based on increased knee symptom severity – typically without worsening radiographic severity (80%). ConclusionRadiographic severity predisposed a knee to esKOA. However, worsening knee symptoms led to the development of incident esKOA. If investigators want to increase the chance of identifying incident esKOA as an outcome, they should enrich their study samples with people with moderate-to-severe radiographic osteoarthritis. Our findings also highlight the potential reversibility of esKOA (a knee that is classified with esKOA but later is not classified with esKOA). Reversibility is not a flaw of an outcome defining esKOA but rather a desirable clinical outcome to demonstrate a therapeutic intervention can help people with esKOA improve their knee symptoms and delay a knee replacement.

Association of synovial expression of growth and differentiation factor 5 (GDF5) with radiographic severity of knee osteoarthritis

ObjectivesThe growth and differentiation factor 5 (GDF5) gene plays a significant role in facilitating chondrogenesis, and GDF5 polymorphism is a genetic factor contributing to osteoarthritis (OA). However, the role of GDF5 expression in the synovial membrane remains unclear. The aim of this study was to determine the expression of GDF5 in the synovium in patients with primary knee OA. Materials and methodsThirty patients scheduled for total knee arthroplasty were enrolled. Patients were grouped according to the Kellgren and Lawrence classification (KL) as grade 3 (15 patients) and grade 4 (15 patients). Synovial tissue was collected, and the GDF5 expression level was determined by real-time PCR. Ten synovial samples were randomly selected to evaluate the degree of synovitis. ResultsBaseline characteristics did not differ between the two groups. The expression of GDF5 was significantly higher in the KL4 group (median expression 3.50, range 1.45–13.62) than in the KL3 group (median expression 1.81, range 0–9.46) (p value = 0.02). Histological staining of the synovium indicated low-grade synovitis in both groups. ConclusionsGDF5 expression in the synovium was positively associated with the radiographic severity of knee OA. The difference in GDF5 expression between the KL3 and KL4 groups supports the hypothesis that, through GDF5, the synovium may have important roles in cartilage maintenance and homeostasis in primary knee OA.

Associations between metabolic factors and radiographic knee osteoarthritis in early disease - a cross-sectional study of individuals with knee pain

ObjectiveMetabolic factors have been shown to be associated to severe radiographic knee osteoarthritis (RKOA). However, more knowledge is needed in early clinical knee osteoarthritis (KOA). The aim was to study associations between metabolic factors and radiographic knee osteoarthritis (OA) in individuals with knee pain. A second aim was to study associations between metabolic factors and RKOA in those with normal BMI and in those overweight/obese, respectively.MethodThis cross-sectional study included 282 individuals with knee pain (without cruciate ligament injury) and aged 30–67 years, and 70% women. Waist circumference, body mass index (BMI), proportion of fat and visceral fat area (VFA) were assessed. RKOA was defined as Ahlbäck grade 1 in at least one knee. Fasting blood samples were taken and triglycerides, cholesterol (total, low density lipoprotein (LDL) and high density lipoprotein (HDL)), C-reactive protein (CRP), glucose, HbA1C were analysed. Metabolic syndrome was defined in accordance with the International Diabetes Federation (IDF). Associations were analysed by logistic regression.ResultsIndividuals with RKOA were older, had higher BMI, higher VFA, larger waist circumference and had increased total cholesterol, triglycerides and LDL-cholesterol, but not fasting glucose. There was no difference between the group with RKOA vs. non-radiographic group regarding the presence of metabolic syndrome. In a subgroup analysis of individuals with normal BMI (n = 126), those with RKOA had higher VFA, more central obesity, higher levels of CRP and total cholesterol, compared with individuals without RKOA. In individuals with obesity, age was the only outcome associated to RKOA.ConclusionThere were clear associations between metabolic factors and RKOA in individuals with knee pain, also in those with normal BMI. In individuals with obesity age was the only variable associated to RKOA.Trial registration:clinicalTrials.gov Identifier: NCT04928170.

Gait-related self-efficacy is directly associated with daily step counts in individuals with knee osteoarthritis

BackgroundIn addition to physical factors, psychological factors such as self-efficacy (SE) reportedly affect physical activity (PA) levels in individuals with knee osteoarthritis (OA). However, the relationship between PA and SE for walking tasks in patients with knee OA remains unclear. The present study aimed to investigate the direct and indirect pathways of SE for walking tasks and the influence of previously reported factors on PA level in individuals with knee OA. MethodsA cross-sectional design was employed. Eighty-five individuals with knee OA were enrolled. The daily step count (Steps) was considered an objective level of PA. The SE for the walking task was assessed using a modified Gait Efficacy Scale (mGES). Data on gait speed (GS), the visual analog scale (VAS) score for knee pain, Kellgren–Lawrence (K–L) grade of radiographic severity of knee OA, age, and body mass index were collected. Path analysis was performed to investigate the direct and indirect effects of these variables on Steps. ResultsAfter exclusion, 70 participants were included. The alternative model, which included Steps, mGES, GS, VAS, K–L grade, and age, showed a good fit. mGES and age had a direct effect on Steps (standardized path coefficients: 0.337 and −0.542, respectively), while the other variables had indirect effects. ConclusionsThe SE for walking tasks was directly associated with Steps representative of the PA level. This finding suggests that SE for the walking task may be important in improving PA levels in individuals with knee OA.

Association Between Walking for Exercise and Symptomatic and Structural Progression in Individuals With Knee Osteoarthritis: Data From the Osteoarthritis Initiative Cohort.

To assess the relationship between walking for exercise and symptomatic and structural disease progression in individuals with knee osteoarthritis (OA). We assessed a nested cohort of participants age 50 years or older within the Osteoarthritis Initiative, a community-based observational study in which subjects were enrolled between 2004 and 2006. We focused on 4 dichotomous outcomes from baseline to the 48-month visit, involving determination of the frequency of knee pain and radiographic severity of knee OA on posteroanterior semiflexed knee radiographs. The outcomes assessed included 1) new frequent knee pain, 2) worsening of radiographic severity of knee OA based on the Kellgren/Lawrence grade, 3) progression of medial joint space narrowing, and 4) improved frequent knee pain. We used a modified version of the Historical Physical Activity Survey Instrument to ascertain those subjects who reported walking for exercise after age 50 years. The survey was administered at the 96-month visit (2012-2014). Of 1,212 participants with knee OA, 45% were male and 73% reported walking for exercise. The mean ± SD age was 63.2 ± 7.9 years, and the mean ± SD body mass index was 29.4 ± 4.6 kg/m2 . The likelihood of new frequent knee pain was reduced in participants with knee OA who walked for exercise as compared to those who were non-walkers (odds ratio [OR] 0.6, 95% confidence interval [95% CI] 0.4-0.8), and progression of medial joint space narrowing was less common in walkers compared to non-walkers (OR 0.8, 95% CI 0.6-1.0). In individuals with knee OA who were age 50 years or older, walking for exercise was associated with less frequent development of knee pain. These findings support the notion that walking for exercise should be encouraged for people with knee OA. Furthermore, we offer a proof of concept that walking for exercise could be disease modifying, which warrants further study.

Metabolomics with severity of radiographic knee osteoarthritis and early phase synovitis in middle-aged women from the Iwaki Health Promotion Project: a cross-sectional study

BackgroundOsteoarthritis (OA) is one of the costliest and most disabling forms of arthritis, and it poses a major public health burden; however, its detailed etiology, pathophysiology, and metabolism remain unclear. Therefore, the purpose of this study was to investigate the key plasma metabolites and metabolic pathways, especially focusing on radiographic OA severity and synovitis, from a large sample cohort study.MethodsWe recruited 596 female volunteers who participated in the Iwaki Health Promotion Project in 2017. Standing anterior-posterior radiographs of the knee were classified by the Kellgren-Lawrence (KL) grade. Radiographic OA was defined as a KL grade of ≥ 2. Individual effusion-synovitis was scored according to the Whole-Organ Magnetic Resonance Imaging Scoring System. Blood samples were collected, and metabolites were extracted from the plasma. Metabolome analysis was performed using capillary electrophoresis time-of-flight mass spectrometry. To investigate the relationships among metabolites, the KL grade, and effusion-synovitis scores, partial least squares with rank order of groups (PLS-ROG) analyses were performed.ResultsAmong the 82 metabolites examined in this assay, PLS-ROG analysis identified 42 metabolites that correlated with OA severity. A subsequent metabolite set enrichment analysis using the significant metabolites showed the urea cycle and tricarboxylic acid cycle as key metabolic pathways. Moreover, further PLS-ROG analysis identified cystine (p = 0.009), uric acid (p = 0.024), and tyrosine (p = 0.048) as common metabolites associated with both OA severity and effusion-synovitis. Receiver operating characteristic analyses showed that cystine levels were moderately associated with radiographic OA (p < 0.001, area under the curve 0.714, odds ratio 3.7).ConclusionLarge sample metabolome analyses revealed that cystine, an amino acid associated with antioxidant activity and glutamate homeostasis, might be a potential metabolic biomarker for radiographic osteoarthritis and early phase synovitis.

Walking-related knee contact forces and associations with knee pain across people with mild, moderate and severe radiographic knee osteoarthritis: a cross-sectional study

To investigate knee contact forces (KCFs), and their relationships with knee pain, across grades of radiographic knee osteoarthritis (OA) severity. Cross-sectional exploratory analysis of 164 participants with medial knee OA. Radiographic severity was classified as mild (grade 2), moderate (grade 3) or severe (grade 4) using the Kellgren & Lawrence (KL) scale. Walking knee pain was assessed using an 11-point numerical rating scale. External knee adduction moment (external KAM) and internal muscle forces were used to calculate medial, lateral and total KCFs using a musculoskeletal computational model. Force-time series across stance phase of gait were compared across KL grades using Statistical Parametric Mapping. Associations between KCFs and pain across KL grades were assessed using linear models. Medial KCFs during early and middle stance were higher in participants with KL3 and KL4 compared to those with KL2. In contrast, lateral KCFs were higher in those with KL2 compared to KL3 and KL4 in middle to late stance. The external loading component (i.e., KAM) of the medial KCF during middle to late stance was also greater in participants with KL3 and KL4 compared to those with KL2, whereas the internal (i.e., muscle) component was greater in those with KL3 and KL4 compared to KL3 during early stance. There were no associations between medial KCF and knee pain in any KL grade. Medial and lateral KCFs differ between mild, moderate and severe radiographic knee OA but are not associated with knee pain severity for any radiographic OA grade.

External validation of an artificial intelligence tool for radiographic knee osteoarthritis severity classification

PurposeTo externally validate an artificial intelligence (AI) tool for radiographic knee osteoarthritis severity classification on a clinical dataset. MethodThis retrospective, consecutive patient sample, external validation study used weight-bearing, non-fixed-flexion posterior-anterior knee radiographs from a clinical production PACS. The index test was ordinal Kellgren-Lawrence grading by an AI tool, two musculoskeletal radiology consultants, two reporting technologists, and two resident radiologists. Grading was repeated by all readers after at least four weeks. Reference test was the consensus of the two consultants. The primary outcome was quadratic weighted kappa. Secondary outcomes were ordinal weighted accuracy, multiclass accuracy and F1-score. Results50 consecutive patients between September 24, 2019 and October 22, 2019 were retrospectively included (3 excluded) totaling 99 knees (1 excluded). Quadratic weighted kappa for the AI tool and the consultant consensus was 0.88 CI95% (0.82–0.92). Agreement between the consultants was 0.89 CI95% (0.85–0.93). Intra-rater agreements for the consultants were 0.96 CI95% (0.94–0.98) and 0.94 CI95% (0.91–0.96) respectively. For the AI tool it was 1 CI95% (1–1). For the AI tool, ordinal weighted accuracy was 97.8% CI95% (96.9–98.6 %). Average multiclass accuracy and F1-score were 84% (83/99) CI95% (77–91%) and 0.67 CI95% (0.51–0.81). ConclusionsThe AI tool achieved the same good-to-excellent agreement with the radiology consultant consensus for radiographic knee osteoarthritis severity classification as the consultants did with each other.

Increased serum AXL is associated with radiographic knee osteoarthritis severity.

ObjectiveTo investigate the expression and clinical significance of serum soluble AXL in patients with radiographic knee osteoarthritis (KOA).MethodsThere were 183 patients with KOA who were selected and divided based on the Kellgren‐Lawrence (KL) score into KL 0 subgroups (n = 42), KL I‐II subgroups (n = 90), and KL III‐IV subgroups (n = 51). Healthy volunteers (n = 170) in our hospital were selected with matched age and gender as the control group. AXL level in serum was detected by enzyme‐linked immunosorbent assay. The correlation between serum AXL with severity and clinical indicators of osteoarthritis was analyzed.ResultsThe level of serum AXL was significantly higher in the osteoarthritis group than that in the control group (P < .05). In the osteoarthritis patients, serum AXL level was increased with the increase of KL score. Serum AXL level was positively correlated with age, body mass index, erythrocyte sedimentation rate, serum C‐reactive protein, cartilage oligomeric protein, matrix metalloproteinase‐13, and transforming growth factor‐β1 levels. The cut‐off value for serum AXL was determined as 33.375 ng/mL by receiver operating curve analysis.ConclusionThe level of serum AXL in patients with osteoarthritis is significantly higher than in healthy controls, and is closely related to the severity of radiographic osteoarthritis.

Mild knee osteoarthritis predicts dissatisfaction after total knee arthroplasty: a prospective study of 186 patients aged 65 years or less with 2-year follow-up

Background and aimsThe incidence of total knee arthroplasty (TKA) is increasing, especially among younger working-age patients. However, dissatisfaction rates in this population are higher than among older patients. The aim of this study was to assess the rates of dissatisfaction and persistent pain after TKA and to evaluate those factors that predict these outcomes.Material and methodsIn total, 186 patients undergoing unilateral TKA aged 65 years or less were enrolled into this prospective observational study with 2-year follow-up. To assess the outcome, the visual analogue scales regarding satisfaction and persistent pain at rest and during exercise were used. In addition, the association between patients´ demographics, radiographic severity of knee osteoarthritis (OA), patient-reported outcome measures (PROMs) and dissatisfaction and persistent pain were tested by univariate logistic regression analysis. Mild OA was defined as Kellgren-Lawrence (KL) grade 2 and severe OA as KL grade 3–4. Furthermore, multiple logistic regression analysis was also conducted to test statistically significant relations.ResultsAfter 2 years, 12 % (n = 23) of patients were dissatisfied with the outcome of TKA, 27 % (n = 50) reported persistent pain during exercise and 10 % (n = 18) at rest. Patients with mild knee OA were significantly more dissatisfied (28.6 %) than patients with more severe OA (8.7 %) (p = 0.003). Younger patients had an increased risk for both dissatisfaction and persistent pain. Apart from KOOS Quality of Life, poor preoperative KOOS subscores were also predictive for these outcomes.ConclusionMild radiographic knee OA was the main predicting factor for dissatisfaction after TKA. Thus, performing TKA for such patients should be carefully considered. Furthermore, these patients should be informed about the increased risk for dissatisfaction and the same seems to apply to younger patients. Interestingly, when TKA is performed for patients with more severe knee OA, the satisfaction rates seem to be somewhat higher than those previously reported.Trial registrationThe study was retrospectively registered with ClinicalTrials.gov (registration number NCT03233620) on 28 July 2017.

Association of Intermittent and Constant Knee Pain Patterns With Knee Pain Severity and With Radiographic Knee Osteoarthritis Duration and Severity.

To examine the relation of knee pain patterns to pain severity and to radiographic osteoarthritis (OA) severity and duration. The Multicenter Osteoarthritis Study is a longitudinal cohort of older adults with or at risk of knee OA. Participants' Intermittent and Constant Osteoarthritis Pain (ICOAP) scores were characterized as 1) no intermittent or constant pain, 2) intermittent pain only, 3) constant pain only, and 4) a combination of constant and intermittent pain. Knee pain severity was assessed using the Western Ontario andMcMaster Universities Osteoarthritis Index(WOMAC) pain subscale and a visual analog scale (VAS). Radiographic knee OA (ROA) severity was defined as Kellgren/Lawrence grade ≥2, and ROA duration was defined according to the clinic visit at which ROA was first noted. We assessed the relation of ICOAP pain patterns to knee pain severity, ROA severity, and ROA duration using regression models with generalized estimating equations. There were 2,322 participants (mean age 68.8 years, body mass index 31.0 kg/m2 , 60% female). Higher ICOAP pain patterns, i.e., a mix of constant and intermittent pain, were associated with greater WOMAC pain severity compared with those patients without either pain pattern (odds ratio [OR] 43.2 [95% confidence interval (95% CI) 26.4-61.3]). Results were similar for the VAS (OR 71.2 [95% CI 45.7-110.9]). Those patients with more severe and longer duration of ROA were more likely to have a mix of constant and intermittent pain compared with those without either pain (OR 3.7 [95% CI 3.1-4.6] and OR 2.9 [95% CI 2.5-3.5], respectively). Knee pain patterns are associated with radiographic disease stage and duration, as well as pain severity, highlighting the fact that pain patterns are important for understanding symptomatic disease progression.

Resistin induces chemokine and matrix metalloproteinase production via CAP1 receptor and activation of p38-MAPK and NF-κB signalling pathways in human chondrocytes.

Adipokine resistin is highly expressed in the serum and synovial uid (SF) of patients with knee osteoarthritis (KOA) but its pathogenic role in KOA remains unclear. We aimed to explore the mechanism of resistin/CAP1 in human KOA chondrocytes. We enrolled 103 patients with radiographic KOA and 86 healthy participants as controls. Resistin levels in serum and SF were determined by enzyme-linked immunosorbent assay (ELISA). CAP1 expression was measured in cartilage tissues using immunohistochemistry, quantitative real-time polymerase chain reaction (qRT-PCR), and western blot. Effects of resistin on chondrocytes and CAP1 were evaluated via qRT-PCR and co-immunoprecipitation. The roles of CAP1, p38-MAPK, and NF-κB signalling pathways in KOA development were evaluated using adenovirus-mediated CAP1 short hairpin RNA, qRT-PCR, western blot, and ELISA. Resistin expression in serum and SF was elevated in severe radiographic KOA. CAP1 levels were higher in KOA cartilage and were positively correlated with resistin expression. Resistin promoted CCL3, CCL4, MMP13, and ADAMTS-4 expression through the CAP1 receptor. Resistin also directly bound to CAP1, as confirmed by co-immunoprecipitation. CAP1 knockdown in chondrocytes attenuated resistin-induced expression of CCL3, CCL4, MMP13, and ADAMTS-4 and activated p38-MAPK and NF-κB signalling pathways. Resistin binds CAP1 and upregulates the expression of proinflammatory cytokines and matrix-degrading enzymes via p38-MAPK and NF-κB signalling in human chondrocytes.

Knee-related disability was largely influenced by cognitive factors and disturbed body perception in knee osteoarthritis

The aim of this study was to explore the existence of subgroups in a cohort of people with knee osteoarthritis (OA) based upon data from multiple pain-related variables and to profile identified clusters according to levels of pain intensity and knee-related disability. Three hundred and three people with knee OA were recruited. Latent profile analysis was used to confirm the optimal number of knee OA subgroups. Body mass index, radiographic knee OA severity, pain catastrophizing, pain related self-efficacy, and knee specific self-perception, were incorporated into the model. Cluster, demographic and clinical variables were compared between the resulting classes. Four distinct classes were identified. Cluster 1 (28.7%) represented early radiographic OA, and moderate pain intensity, disability and cognitive and perceptual dysfunction. Cluster 2 (18.8%) showed advanced radiographic OA, and moderate pain intensity, disability and cognitive and perceptual dysfunction. Cluster 3 (34.3%) represented various levels of radiographic OA, and the lowest pain intensity, disability and cognitive and perceptual dysfunction. Cluster 4 (18.1%) represented various levels of radiographic OA, the highest disability and cognitive and perceptual dysfunction. Considering cognitive factors and disturbed body perception may help to explain the phenomenon of the discrepancy between the knee-related disability and the severity of radiographic knee OA.