Osteoarthritis Status Research Articles

Prevalence and socioeconomic status of osteoarthritis among adult population in and around Chennai: A case study

Introduction and Aim: One of the more common degenerative illnesses in the adult population is osteoarthritis (OA). Many etiological agents are responsible for this common disorder like aging, calcium deficiency, inflammatory syndromes, etc.,With reference to this, preventive measures can be adopted by proper diagnosis and treatment at the right stage. The goal of this research was to evaluate the causes of osteoarthritis of the knee in adults and to identify the inflammatory biomarkers. Materials and Methods: A population?based, case study among 600 adultsattending local hospitals inChennai and Kanchipuram district, Tamilnadu, India, was cross-examined from January 2017 to December 2018. All the data related to the study were collected by the postgraduate students, skilled health workers according to thedirection of thecorresponding author. Printedquestionairesand informed approval were obtained from all study participants. Diagnosing criteria for OA wereadopted from the Rheumatology College of America, and it was confirmed and verified in the region. Results: Around 600 adult patients were questioned, with 27.1 % having knee OA.The following measures like age, tobacco habit, illiteracy, lower socioeconomic class, positive family history of OA, diabetes, and hypertension were found to be highly linked with OA knee significantly in age greater than 50 in females (P < 0.05). Conclusion: The risk of OA was high in this area and serum biomarkers were evaluated. In the present study, the IL-2,IL-5,IL-6, and IL-10 were considered as biomarkers for osteoarthritis in acute and chronic stages. As a result, an effective preventative approach is required to reduce this burden.

Correlation of systemic metabolic inflammation with knee osteoarthritis.

The aim of this study was to analyze local and systematic inflammatory status in knee osteoarthritis (KOA), focusing on intra-articular and remote adipose tissue depots, and to explore its potential association with metabolic syndrome (MetS). Patients (n = 27) with end-stage KOA were enrolled in the study and samples from infrapatellar fat pad (IFP), synovium, subcutaneous adipose tissue (SAT), synovial fluid (SF), and serum were collected. In homogenates from the tissues, mRNA expression of developmental endothelial locus-1 (DEL-1) was determined. Interleukin 6 (IL-6) and interleukin 8 (IL-8) were measured in tissues and SF and serum samples by enzyme-linked immunosorbent assay. Fifteen patients fulfilled MetS criteria (w-MetS group) and 12 did not (non-MetS). In the entire population, IL-6 levels were significantly higher in IFP compared to synovium (median (interquartile range), 26.05 (26.16) vs. 15.75 (14.8) pg/mg of total protein, p = 0.043), but not to SAT (17.89 (17.9) pg/mg); IL-8 levels were significantly higher in IFP (17.3 (19.3) pg/mg) and SAT (24.2 (26) pg/mg) when compared to synovium (8.45 (6.17) pg/mg) (p = 0.029 and < 0.001, respectively). Significantly higher IL-6 concentrations in SF were detected in w-MetS patients compared to non-MetS (194.8 (299) vs. 64.1 (86.9) pg/ml, p = 0.027). Finally, DEL-1 mRNA expression was higher in IFP compared to synovium (eightfold, p = 0.019). Our findings support the critical role of IFP in knee joint homeostasis and progression of KOA. Furthermore, in KOA patients w-MetS, SAT is thought to play an important role in intra-knee inflammation via secretion of soluble inflammatory mediators, such as IL-6.

Stromal Vascular Fraction for Knee Osteoarthritis - An Update.

Orthobiologics never cease to cause popularity within the medical science field, distinctly in regenerative medicine. Recently, adipose tissue has been an object of interest for many researchers and medical experts due to the fact that it represents a novel and potential cell source for tissue engineering and regenerative medicine purposes. Stromal vascular fraction (SVF), for instance, which is an adipose tissue-derivative, has generated optimistic results in many scenarios. Its biological potential can be harnessed and administered into injured tissues, particularly areas in which standard healing is disrupted. This is a typical feature of osteoarthritis (OA), a common degenerative joint disease which is outlined by persistent inflammation and destruction of surrounding tissues. SVF is known to carry a large amount of stem and progenitor cells, which are able to perform self-renewal, differentiation, and proliferation. Furthermore, they also secrete several cytokines and several growth factors, effectively sustaining immune modulatory effects and halting the escalated pro-inflammatory status of OA. Although SVF has shown interesting results throughout the medical community, additional research is still highly desirable in order to further elucidate its potential regarding musculoskeletal disorders, especially OA.

Sex differences in the regularity and symmetry of gait in older adults with and without knee osteoarthritis

BackgroundThree-dimensional (3D) motion measured at the lower back during walking can describe the regularity and symmetry of gait that may be related to osteoarthritis (OA) and functional status. However, gait speed and inherent sex differences, regardless of the presence of OA, may confound these measures. Therefore, there is a need to understand the effect of OA separately among males and females, without the confounding influence of gait speed. ObjectiveTo investigate the difference in 3D gait regularity and symmetry measures between gait speed-matched males and females with and without knee OA. MethodGait regularity and symmetry were computed as autocorrelations of pelvic accelerations during treadmill walking in four groups of older adults: healthy asymptomatic females (AsymF; n = 44), healthy asymptomatic males (AsymM; n = 45), females diagnosed with knee OA (OAF; n = 44), and males diagnosed with knee OA (OAM; n = 45). Data were obtained from a larger research database, allowing for the matching of gait speed between groups. The main effect of OA, sex, and interaction effect between them was examined for the 3D gait regularity and symmetry measures at an alpha level of 0.05. ResultsThere was no main effect of OA on any variable, but there was a significant main effect of sex on mediolateral and anteroposterior gait regularity measures. Specifically, females demonstrated significantly greater gait regularity, most notably in the mediolateral directions compared to males. ConclusionOlder adult females were found to display significantly greater mediolateral gait regularity as compared to males, regardless of the presence of OA. Further, this difference exists among matched gait speeds, suggesting it is not the result of gait speed. Overall, these results highlight the importance of sex-specific analyses and considering gait speed when examining gait acceleration patterns near the center of mass for both cross sectional and longitudinal gait assessments.

A novel approach to studying early knee osteoarthritis illustrates that bilateral medial tibiofemoral osteoarthritis is a heritable phenotype: an offspring study.

To assess the potential of studying offspring of people with and without knee osteoarthritis to understand the risk factors and heritability for knee osteoarthritis. We selected two groups of Osteoarthritis Initiative (OAI) participants from one clinical site: (1) participants with bilateral radiographic medial tibiofemoral osteoarthritis and (2) those without tibiofemoral osteoarthritis. We then invited biological offspring ≥ 18years old to complete an online survey that inquired about osteoarthritis risk factors and symptoms. Among the survey respondents, we recruited ten offspring of members from each group for a clinic visit with bilateral knee posterior-anterior radiographs and magnetic resonance imaging of the right knee. We established contact with 269/413 (65%) eligible OAI participants. Most (227/269, 84%) had ≥ 1 eligible biological offspring, and 213 (94%) were willing to share information about the new family study with their offspring. Our survey was completed by 188 offspring from 110 OAI participants: mean age of 43.0 (10.4) years, mean body mass index of 23.7 (5.9) kg/m2, 65% female. Offspring obesity (OR = 2.7, 95% CI 1.0-7.3), hypertension (OR = 3.7, 95% CI 1.2-11.3), and Heberden's nodes (OR = 3.6, 95% CI 1.0-13.2) were associated with parental osteoarthritis status; however, adjusted models were not statistically significant. Radiographic tibiofemoral osteoarthritis (16/18 knees vs. 2/20 knees) and meniscal abnormalities (7/9 vs. 2/10 index knees) were more common among offspring with parental osteoarthritis status than not. We established the potential of a novel offspring study design within the OAI, and our results are consistent with bilateral radiographic medial tibiofemoral osteoarthritis being a heritable phenotype of osteoarthritis.

Discovering Knee Osteoarthritis Imaging Features for Diagnosis and Prognosis: Review of Manual Imaging Grading and Machine Learning Approaches.

Knee osteoarthritis (OA) is a deliberating joint disorder characterized by cartilage loss that can be captured by imaging modalities and translated into imaging features. Observing imaging features is a well-known objective assessment for knee OA disorder. However, the variety of imaging features is rarely discussed. This study reviews knee OA imaging features with respect to different imaging modalities for traditional OA diagnosis and updates recent image-based machine learning approaches for knee OA diagnosis and prognosis. Although most studies recognized X-ray as standard imaging option for knee OA diagnosis, the imaging features are limited to bony changes and less sensitive to short-term OA changes. Researchers have recommended the usage of MRI to study the hidden OA-related radiomic features in soft tissues and bony structures. Furthermore, ultrasound imaging features should be explored to make it more feasible for point-of-care diagnosis. Traditional knee OA diagnosis mainly relies on manual interpretation of medical images based on the Kellgren–Lawrence (KL) grading scheme, but this approach is consistently prone to human resource and time constraints and less effective for OA prevention. Recent studies revealed the capability of machine learning approaches in automating knee OA diagnosis and prognosis, through three major tasks: knee joint localization (detection and segmentation), classification of OA severity, and prediction of disease progression. AI-aided diagnostic models improved the quality of knee OA diagnosis significantly in terms of time taken, reproducibility, and accuracy. Prognostic ability was demonstrated by several prediction models in terms of estimating possible OA onset, OA deterioration, progressive pain, progressive structural change, progressive structural change with pain, and time to total knee replacement (TKR) incidence. Despite research gaps, machine learning techniques still manifest huge potential to work on demanding tasks such as early knee OA detection and estimation of future disease events, as well as fundamental tasks such as discovering the new imaging features and establishment of novel OA status measure. Continuous machine learning model enhancement may favour the discovery of new OA treatment in future.

Effects of Obesity Reduction on Physical Function, Inflammation and Osteoarthritis in Older Adults

Age-related increases in chronic inflammation lead to reduced physical function via damage to muscle and joints and contribute to osteoarthritis (OA) risk. Obesity in older adults with OA further exacerbates inflammatory damage. Whether obesity reduction can lessen inflammation and improve OA is unknown; however, novel biomarkers may provide an answer. We completed a 6-mo. weight loss intervention (-500 kcal/day), studying blood biomarkers of inflammation and cartilage damage along with physical function in obese older adults with (OA+; n=39) and without an OA diagnosis (OA-; n=20). Participants were aged > 60 yrs (mean = 70.2±6.0) and obese (BMI =34.6±4.7 kg/m2). At endpoint, weight loss was -6.3±4.0% and -5.8±4.1% in OA+ and OA-, respectively, with no group difference. Change scores for function for OA+ and OA- were: Short Physical Performance Battery score (+1.7±1.3 and +2.1±1.5), 8 ft up and go (-0.7±1.0 and -0.9±1.12 sec) and 6 min walk (+31.4±105.1 and +39.5±57.4 meters). All improved from baseline (p<0.05), with no group difference. Concerning blood biomarkers, there was a decrease (p<0.05) in cartilage oligomeric matrix protein (COMP: OA biomarker), indicating a potential benefit for OA. Change in COMP also differed between groups; OA- had a greater (p<0.05) reduction than OA+. Pooled results showed improved adiponectin (p<0.05), with no group difference. There were no changes for CRP, CTX-1, IL-6 and TNF-α. Our novel findings link early intervention with better reduction of OA risk and inflammation in obese older adults and also show important benefits for improved physical function regardless of OA status.

The Survey of Knee Osteoarthritis in the Population over Age 50 Visited in the Health Bus in Kermanshah, Iran.

Along with an aging population worldwide, knee osteoarthritis (KOA), which is the main cause of musculoskeletal pain and disability in the elderly and decreases the quality of life, is prevalent, and their impact is widespread. This study aimed to evaluate the knee osteoarthritis status among the population over age 50 in Kermanshah, Iran. The research community consisted of the population who has been visited in the health bus in Kermanshah in 2016-2017, of which 589 were chosen by an available sampling method. A WOMAC questionnaire was used to determine the prevalence of knee osteoarthritis. The prevalence of knee stiffness rate after sitting, lying down, or resting during the day among women and men were 40.7% and 20.5%, respectively. According to the findings, the highest prevalence rate of knee pain was in subjects with a BMI higher than 30 (31.6%) and BMI 25–30 (24.5%). 39.2% of the subjects never experienced knee pain, 16.6% monthly, 13.4% once a week, 20.4% daily, and 10.4% of them had prolonged knee pain experience. The prevalence of gender-based knee pain was 60.5% among women and 38.6% among men. 30.5% of women and 61.4% of men never experienced knee pain.

Subchondral Bone Length in Knee Osteoarthritis: A Deep Learning-Derived Imaging Measure and Its Association With Radiographic and Clinical Outcomes.

To develop a bone shape measure that reflects the extent of cartilage loss and bone flattening in knee osteoarthritis (OA) and test it against estimates of disease severity. A fast region-based convolutional neural network was trained to crop the knee joints in sagittal dual-echo steady-state magnetic resonance imaging sequences obtained from the Osteoarthritis Initiative (OAI). Publicly available annotations of the cartilage and menisci were used as references to annotate the tibia and the femur in 61 knees. Another deep neural network (U-Net) was developed to learn these annotations. Model predictions were compared to radiologist-driven annotations on an independent test set (27 knees). The U-Net was applied to automatically extract the knee joint structures on the larger OAI data set (n = 9,434 knees). We defined subchondral bone length (SBL), a novel shape measure characterizing the extent of overlying cartilage and bone flattening, and examined its relationship with radiographic joint space narrowing (JSN), concurrent pain and disability (according to the Western Ontario and McMaster Universities Osteoarthritis Index), as well as subsequent partial or total knee replacement. Odds ratios (ORs) and 95% confidence intervals (95% CIs) for each outcome were estimated using relative changes in SBL from the OAI data set stratified into quartiles. The mean SBL values for knees with JSN were consistently different from knees without JSN. Greater changes of SBL from baseline were associated with greater pain and disability. For knees with medial or lateral JSN, the ORs for future knee replacement between the lowest and highest quartiles corresponding to SBL changes were 5.68 (95% CI 3.90-8.27) and 7.19 (95% CI 3.71-13.95), respectively. SBL quantified OA status based on JSN severity and shows promise as an imaging marker in predicting clinical and structural OA outcomes.

Fecal metabolomics reveals products of dysregulated proteolysis and altered microbial metabolism in obesity-related osteoarthritis

The objective of this exploratory study was to determine if perturbations in gut microbial composition and the gut metabolome could be linked to individuals with obesity and osteoarthritis (OA). Fecal samples were collected from obese individuals diagnosed with radiographic hand plus knee OA (n=59), defined as involvement of at least 3 joints across both hands, and a Kellgren-Lawrence (KL) grade 2-4 (or total knee replacement) in at least one knee. Controls (n=33) were without hand OA and with KL grade 0-1 knees. Fecal metabolomes were analyzed by a UHPLC/Q Exactive HFx mass spectrometer. Microbiome composition was determined in fecal samples by 16S ribosomal RNA amplicon sequencing (rRNA-seq). Stepwise logistic regression models were built to determine microbiome and/or metabolic characteristics of OA. Untargeted metabolomics analysis indicated that OA cases had significantly higher levels of di- and tripeptides and significant perturbations in microbial metabolites including propionic acid, indoles, and other tryptophan metabolites. Pathway analysis revealed several significantly perturbed pathways associated with OA including leukotriene metabolism, amino acid metabolism and fatty acid utilization. Logistic regression models selected metabolites associated with the gut microbiota and leaky gut syndrome as significant predictors of OA status, particularly when combined with the rRNA-seq data. Adults with obesity and knee plus hand OA have distinct fecal metabolomes characterized by increased products of proteolysis, perturbations in leukotriene metabolism, and changes in microbial metabolites compared with controls. These metabolic perturbations indicate a possible role of dysregulated proteolysis in OA.

Bone in osteoarthritis: imaging and interventions.

To review the recent literature on bone in osteoarthritis (OA), with a focus on imaging and intervention studies. Most studies focused on knee OA; hip and hand studies were uncommon. Bone shape studies demonstrated that shape changes precede radiographic OA, predict joint replacement, and have demonstrated high responsiveness. Novel quantitative 3D imaging markers (B-score) have better characterized OA severity, including preradiographic OA status. The addition of computerized tomography-derived 3D metrics has improved the prediction of hip joint replacement when compared to radiographs alone.Recent studies of bisphosphonates for knee OA have reported no benefits on pain or bone marrow lesion (BML) size. A meta-analysis on Vitamin D supplementation in knee OA suggested minimal symptom improvement and no benefits on the structure. Cathepsin K inhibition demonstrated reduction in OA bone change progression, but with no symptom benefit. Studies of injections of bone substitutes into BMLs (subchondroplasty) have generally been small and potential benefits remain unclear. Subchondral bone features are associated with pain, incidence and progression of OA. Recent studies have validated quantitative bone shape as a biomarker for OA trials. Trials of bone-targeted OA therapies have been disappointing although cathepsin K inhibition may slow structural progression.

Mechanical metrics may show improved ability to predict osteoarthritis compared to T1rho mapping

Changes in cartilage structure and composition are commonly observed during the progression of osteoarthritis (OA). Importantly, quantitative magnetic resonance imaging (MRI) methods, such as T1rho relaxation imaging, can noninvasively provide in vivo metrics that reflect changes in cartilage composition and therefore have the potential for use in early OA detection. Changes in cartilage mechanical properties are also hallmarks of OA cartilage; thus, measurement of cartilage mechanical properties may also be beneficial for earlier OA detection. However, the relative predictive ability of compositional versus mechanical properties in detecting OA has yet to be determined. Therefore, we developed logistic regression models predicting OA status in an ex vivo environment using several mechanical and compositional metrics to assess which metrics most effectively predict OA status. Specifically, in this study the compositional metric analyzed was the T1rho relaxation time, while the mechanical metrics analyzed were the stiffness and recovery (defined as a measure of how quickly cartilage returns to its original shape after loading) of the cartilage. Cartilage recovery had the best predictive ability of OA status both alone and in a multivariate model including the T1rho relaxation time. These findings highlight the potential of cartilage recovery as a non-invasive marker of in vivo cartilage health and motivate future investigation of this metric clinically.

The relationship between common variants in the DPEP1 gene and the susceptibility and clinical severity of osteoarthritis.

Previous studies have provided evidence linking the DPEP1 gene to the risk of osteoarthritis (OA) in Europeans. In this study, we aimed to examine the relationship between DPEP1 gene and the susceptibility and clinical severity of OA in a Chinese Han population. This study comprised two independent samples. For the discovery stage, 1022 patients with knee OA and 1864 controls were recruited. Fourteen tag single nucleotide polymorphisms (SNPs) covering the DPEP1 gene were selected and genotyped. Associated SNPs in the discovery data set were subsequently genotyped in the replication data set consisting of 826 hip OA cases and 1662 controls. Both genotypic and allelic genetic associations were tested. The relationship of significant SNPs to the expression of DPEP1 and its neighboring genes was examined using the GTEx database. A nonsynonymous SNP, rs1126464, was determined to be associated with the disease status of OA in both the discovery and replication stages (odds ratio [OR] 0.75, 95% confidence interval [95% CI] 0.68-0.82, P=7.16×10-11 ). This SNP was further characterized as being significantly related to a higher Kellgren-Lawrence grade in OA patients (OR 0.64, 95% CI 0.55-0.74, P=2.53×10-9 ). According to the GTEx data, SNP rs1126464 was significantly related to the gene expression of 15 genes in multiple types of human tissues. We reported a common DNA variant in the DPEP1 gene that contributes to the risk of OA, providing additional evidence that the DPEP1 gene plays a significant role in the pathological mechanisms of OA.

β-Carotene Status Is Associated with Inflammation and Two Components of Metabolic Syndrome in Patients with and without Osteoarthritis.

This study was conducted to investigate the β-carotene status in osteoarthritis (OA) patients and examine its relationships with the risk of inflammation and metabolic syndrome. OA patients were stratified by obesity based on body fat percentage (obese OA, n = 44; non-obese OA, n = 56), and sixty-nine subjects without OA or obesity were assigned as a non-obese control group. β-carotene, metabolic parameters, and inflammation status were assessed. Obese OA patients exhibited a significantly higher rate of metabolic syndrome (p = 0.02), abdominal obesity (p < 0.01), and lower β-carotene status (p < 0.01) compared with non-obese OA and non-obese controls. After adjusting for potential confounders, β-carotene status (≥0.8 µM) was significantly inversely correlated with the risk of metabolic syndrome (odds ratio = 0.27, p < 0.01), abdominal obesity (odds ratio = 0.33, p < 0.01), high blood pressure (odds ratio = 0.35, p < 0.01), hyperglycemia (odds ratio = 0.45, p < 0.05), and inflammation (odds ratio = 0.30, p = 0.01). Additionally, subjects who had a high β-carotene status with a low proportion of metabolic syndrome when they had a low-grade inflammatory status (p < 0.01). Obese OA patients suffered from a higher prevalence of metabolic syndrome and lower β-carotene status compared to the non-obese controls. A better β-carotene status (≥0.8 µM) was inversely associated with the risk of metabolic syndrome and inflammation, so we suggest that β-carotene status could be a predictor of the risk of metabolic syndrome and inflammation in patients with and without OA.

The impact of diabetes and osteoarthritis on the occurrence of stroke, acute myocardial infarction, and heart failure among older adults with non-valvular atrial fibrillation in Hawaii: a retrospective observational cohort study

BackgroundTo date, little is known about cardiovascular disease risks among older adults with non-valvular atrial fibrillation by their association with diabetes and osteoarthritis status, based on longitudinal data with substantial amounts of non-white individuals. The objective of this study was to examine the risks for three cardiovascular diseases: stroke, acute myocardial infarction (AMI), and heart failure (HF), by diabetes and osteoarthritis status among older adults with non-valvular atrial fibrillation in Hawaii.MethodsWe conducted a retrospective observational cohort study for older adults (65 years and older) with non-valvular atrial fibrillation using the Hawaii Medicare data 2009–2017. Their risks for the three cardiovascular diseases by diabetes and osteoarthritis status (diabetes, osteoarthritis, diabetes and osteoarthritis, and without diabetes and osteoarthritis) were examined by multivariable Cox proportional hazard regression models.ResultsThe analysis included 19,588 beneficiaries followed up for a maximum of 3288 days (diabetes: n = 4659, osteoarthritis: n = 1978, diabetes and osteoarthritis: n = 1230, without diabetes and osteoarthritis: n = 11,721). Among them, those diagnosed with the cardiovascular diseases were identified (stroke: diabetes n = 837, osteoarthritis n = 315, diabetes and osteoarthritis n = 184, without diabetes and osteoarthritis n = 1630)(AMI: diabetes n = 438, osteoarthritis n = 128, diabetes and osteoarthritis n = 118, without diabetes and osteoarthritis n = 603)(HF: diabetes n = 2254, osteoarthritis n = 764, diabetes and osteoarthritis n = 581, without diabetes and osteoarthritis n = 4272). After adjusting for age, sex, race/ethnicity, and other potential confounders, those with diabetes and osteoarthritis had higher risks for HF (hazard ratio: 1.21 95% confidence interval: 1.10–1.33) than those without diabetes and osteoarthritis. They also had higher risks than those with osteoarthritis for HF. Those with diabetes had higher risks for all three cardiovascular diseases than the other three groups.ConclusionsVariation in cardiovascular disease risks for older adults with non-valvular atrial fibrillation in Hawaii exists with diabetes and osteoarthritis status.

Untargeted Fecal Metabolomics to Investigate the Role of the Microbiome and Nutrients in Osteoarthritis

Abstract Objectives The objective of this study was to determine if perturbations in gut microbial composition and the gut metabolome could be linked to individuals with obesity and osteoarthritis (OA). Methods Fecal samples were collected from 92 participants with obesity recruited from the Johnston County Osteoarthritis Project. OA cases (n = 59) had radiographic hand plus knee OA, defined as involvement of at least 3 joints across both hands, and a Kellgren-Lawrence (KL) grade 2–4 in at least one knee. Controls (n = 33) were without hand OA and with KL grade 0–1 knees. Fecal metabolomes were analyzed by a UHPLC/Q Exactive HFx mass spectrometer. Microbiome composition was determined in fecal samples by 16S ribosomal RNA amplicon sequencing (rRNA-seq). Stepwise logistic regression models were built to determine predictors of OA status. Spearman correlations were performed to determine associations between metabolites and microbiota in OA or healthy individuals. Results Untargeted metabolomics analysis indicated that OA cases had significantly higher levels of di- and tri-peptides (P &amp;lt; 0.05), and significant perturbations (P &amp;lt; 0.1) in microbial metabolites. Pathway analysis revealed several significantly perturbed pathways (P &amp;lt; 0.05) associated with OA, including leukotriene metabolism, amino acid metabolism and fatty acid utilization. Logistic regression models selected metabolites associated with the microbiota and leaky gut syndrome as significant predictors of OA status, particularly when combined with the 16S rRNA sequencing data. Omega-3/6 polyunsaturated fatty acids (PUFAs) levels were significantly correlated with the phyla Bacteriodetes and Firmicutes. Conclusions Adults with obesity and OA have distinct fecal metabolomes characterized by perturbations in microbial metabolites, PUFAs, and protein digestion compared with healthy controls. These metabolic perturbations suggest a role of intestinal inflammation and leaky gut in OA. Funding Sources Supported by the Arthritis Foundation, the National Center for Advancing Translational Sciences (NCATS) (UL1TR002489), and the National Institute of Arthritis and Musculoskeletal and Skin Diseases (P30AR072580).

No differences in clinical outcomes and cartilage repair between opening wedge and closed wedge high tibial osteotomies at short-term follow-up: A retrospective case series analysis.

The aim of this study was to assess differences in clinical outcomes and postoperative cartilage repair between opening wedge high tibial osteotomy (OWHTO) and closed wedge HTO (CWHTO) for medial osteoarthritis (OA) of the knee. A total of 90 knees of 76 patients who underwent OWHTO (45 knees of 40 patients) and CWHTO (45 knees of 36 patients) was followed-up for 2 years. Cartilage repair at the medial compartment was arthroscopically classified into the following stages: Stage 1 (no reparative change); Stage 2 (partial coverage with white cartilaginous tissue); and Stage 3 (full coverage with white cartilaginous tissue). Clinical outcomes were assessed using Knee Society scores, and radiographic assessment was carried out by anatomical femorotibial angle (aFTA). Regarding preoperative OA grade, varus alignment, and function score, CWHTO patients showed more advanced OA status than OWHTO patients. Knee scores and function scores were significantly improved after surgery with both HTO procedures (P < 0.05), with no significant difference between the two procedures. Cartilage repair of stage 2 or 3 was found in more than 80% of the subjects in the medial femoral condyle and more than 60% in the medial tibial condyle. However, there were no significant differences between the two HTO procedures. Multivariate logistic regression analysis showed that preoperative International Cartilage Repair Society (ICRS) grade was the only factor affecting cartilage repair. CWHTO improved clinical outcomes and cartilage status as much as OWHTO. Although the effects of cartilage repair on clinical outcomes are unknown, HTO is an effective treatment option even for severe medial OA of the knee.

Changes of synovial fluid biomarker levels after opening wedge high tibial osteotomy in patients with knee osteoarthritis

The purpose of this study was to evaluate the effects of high tibial osteotomy (HTO) on the biological status of knee osteoarthritis (OA) using joint markers in synovial fluid (SF). Fifty patients with medial compartmental OA of the knee who underwent opening wedge HTO were enrolled. Paired SF samples from the affected knee and arthroscopic evaluation of articular cartilage were collected at the time of HTO surgery and the time of plate removal (postoperative 17±4 months). The concentrations of the following SF biomarkers were measured: interleukin (IL)-1β, IL-6, IL-8, IL-10, tumour necrosis factor-α, matrix metalloproteinase (MMP)-2, MMP-3, MMP-9, MMP-13, vascular endothelial growth factor (VEGF), and cartilage oligomeric matrix protein (COMP). The Knee Society Score (KSS) and hip-knee-ankle (HKA) angle were assessed before and 2 years after HTO. The KSS knee and function scores were significantly improved after HTO (mean changes of 36.4 and 23.7, respectively). The mean HKA angle was altered from mechanical varus (-8.6°) to valgus (5.2°). Concentrations of IL-6, IL-8, MMP-2, MMP-3, MMP-13, VEGF, and COMP in SF were significantly decreased after HTO (mean changes of-49.1%,-30.2%,-31.1%,-26.3%,-30.8%,-42.5%, and-13.7% from preoperative baseline, respectively). The cartilage status was improved in 19 cases (38%) after HTO. However, changes of all biomarkers were not significantly different between subjects with and without an improved cartilage status. SF levels of biochemical markers for cartilage degradation and synovial inflammation were altered after HTO, suggesting an improvement in the OA disease state.

Knee Osteoarthritis, Potential Mediators, and Risk of All‐Cause Mortality: Data From the Osteoarthritis Initiative

To assess the relation of symptomatic knee osteoarthritis (OA), knee pain, and radiographic knee OA to All-cause mortality and to identify mediators in the causal pathway. Participants from the Osteoarthritis Initiative were divided into 4 groups: 1) symptomatic knee OA (i.e., both radiographic knee OA [Kellgren/Lawrence grade ≥2] and knee pain); 2) knee pain only; 3) radiographic knee OA only; and 4) neither radiographic knee OA nor knee pain. We examined the relation of knee OA status to All-cause mortality using a multivariable Cox proportional hazards model and assessed the extent to which the association was mediated by disability, physical component summary (PCS) and mental component summary (MCS) scores for quality of life (QoL), and use of oral pain-relief medications (i.e., nonsteroidal antiinflammatory drugs and opioids). Among 4,796 participants, 282 died over the 96-month follow-up period. Compared with those with neither radiographic knee OA nor knee pain, multivariable-adjusted hazard ratios (HRs) of mortality were 2.2 (95% confidence interval [95% CI] 1.6-3.1) for symptomatic knee OA, 0.9 (95% CI 0.6-1.4) for knee pain only, and 2.0 (95% CI 1.4-2.9) for radiographic knee OA only, respectively. Indirect effects (HRs) of symptomatic knee OA on mortality via disability and PCS of QoL were 1.1 (95% CI 1.0-1.4) and 1.2 (95% CI 1.0-1.4), respectively. No apparent mediation effect was observed through either MCS of QoL or oral pain-relief medications use. Participants with either symptomatic or radiographic knee OA were at an increased risk of All-cause mortality. Increased risk of mortality from symptomatic knee OA was partially mediated through its effect on disability and PCS of QoL.

The association of the progression of knee osteoarthritis with high-sensitivity CRP in community-dwelling people-the Yakumo study.

We aimed to investigate the relationship between high-sensitivity CRP (hs-CRP) levels and the knee osteoarthritis (KOA) status and whether high hs-CRP levels predict the progression of clinical KOA in community-dwelling people. We enrolled 247 subjects (male, n = 99; female, n = 148) who participated in the "Yakumo study" at least twice from 2003 to 2008. The KOA was evaluated by knee X-ray using the knee osteoarthritis computer-aided diagnosis (KOACAD) measurement system to obtain the mJSW, the size of the osteophyte area (OPA), and femorotibial angle (FTA). The pain intensity of the knee joint was measured using a visual analog scale (VAS, 0-100). First, we performed a multiple regression analysis to assess the relationship between the initial hs-CRP and mJSW, OPA, FTA, and VAS. Second, we examined the correlated coefficients between the amount of change hs-CRP and radiographic progressions and VAS changes. Third, we divided into two groups. Group H elevated hs-CRP levels (> 0.1mg/dl). We picked up the subject matched to Group H according to BMI, age, sex, and medial mJSW at baseline in a 1:1 ratio; these participants were classified as the control group (Group L). The Mann-Whitney U test was used to compare the demographic data between the two groups. P values of < 0.05 were considered to indicate statistical significance. The initial hs-CRP was a significant explanatory factor for mJSW and VAS change in multiple regression analysis. The change of VAS value negatively correlated with the change of hs-CRP. Besides, the change of hs-CRP did not correlate with the radiographical change. Among these subjects, 55 had elevated hs-CRP levels (> 0.1mg/dl) (Group H). Among the 192 subjects whose hs-CRP levels were ≤ 0.1mg/dl, 55 subjects were matched to patients in Group H according to the age, sex, BMI, and average minimum joint space width (mJSW) at baseline and were used as a control group (Group L). The narrowing of the medial mJSW and the amount of change in OPA in group H were significantly greater than group L. The amount of change in FTA and VAS scores did not differ between the two groups. Hs-CRP levels would be significantly associated with the progression of knee osteoarthritis. Key Points • We investigated the relationship between hs-CRP levels and the progression and the pain of osteoarthritis knee. • We used a KOACAD system, which can measure the medial and lateral joint space narrowing, osteophyte, and femoral-tibia angle from plain radiographs automatically. • Hs-CRP levels were significantly associated with the progression of knee osteoarthritis.