Definition Of Osteoarthritis Research Articles

Comparison of definitions of early knee osteoarthritis for likelihood of progression at 2-year and 5-year follow-up: the Multicenter Osteoarthritis Study

BackgroundPreventing worsening osteoarthritis (OA) in persons with early OA is a major treatment goal. We evaluated if different early OA definitions yielded enough cases of worsening OA within 2–5 years...

Articular cartilage corefucosylation regulates tissue resilience in osteoarthritis.

This study aimed to investigate the glycan structural changes that occur before histological degeneration in osteoarthritis (OA) and to determine the mechanism by which these glycan conformational changes affect cartilage degeneration. An OA model was established in rabbits using mannosidase injection, which reduced high-mannose type N-glycans and led to cartilage degeneration. Further analysis of glycome in human OA cartilage identified specific corefucosylated N-glycan expression patterns. Inhibition of N-glycan corefucosylation in mice resulted in unrecoverable cartilage degeneration, while cartilage-specific blocking of corefucosylation led to accelerated development of aging-associated and instability-induced OA models. We conclude that α1,6 fucosyltransferase is required postnatally to prevent preosteoarthritic deterioration of articular cartilage. These findings provide a novel definition of early OA and identify glyco-phenotypes of OA cartilage, which may distinguish individuals at higher risk of progression.

Articular cartilage corefucosylation regulates tissue resilience in osteoarthritis

This study aimed to investigate the glycan structural changes that occur before histological degeneration in osteoarthritis (OA) and to determine the mechanism by which these glycan conformational changes affect cartilage degeneration. An OA model was established in rabbits using mannosidase injection, which reduced high-mannose type N-glycans and led to cartilage degeneration. Further analysis of glycome in human OA cartilage identified specific corefucosylated N-glycan expression patterns. Inhibition of N-glycan corefucosylation in mice resulted in unrecoverable cartilage degeneration, while cartilage-specific blocking of corefucosylation led to accelerated development of aging-associated and instability-induced OA models. We conclude that α1,6 fucosyltransferase is required postnatally to prevent preosteoarthritic deterioration of articular cartilage. These findings provide a novel definition of early OA and identify glyco-phenotypes of OA cartilage, which may distinguish individuals at higher risk of progression.

Current MR imaging of cartilage in the context of knee osteoarthritis (part1) : Principles and sequences

Magnetic resonance imaging (MRI) is the clinical method of choice for cartilage imaging in the context of degenerative and nondegenerative joint diseases. The MRI-based definitions of osteoarthritis rely on the detection of osteophytes, cartilage pathologies, bone marrow edema and meniscal lesions but currently ascientific consensus is lacking. In the clinical routine proton density-weighted, fat-suppressed 2D turbo spin echo sequences with echo times of 30-40 ms are predominantly used, which are sufficiently sensitive and specific for the assessment of cartilage. The additionally acquired T1-weighted sequences are primarily used for evaluating other intra-articular and periarticular structures. Diagnostically relevant artifacts include magic angle and chemical shift artifacts, which can lead to artificial signal enhancement in cartilage or incorrect representations of the subchondral lamina and its thickness. Although scientifically validated, high-resolution 3D gradient echo sequences (for cartilage segmentation) and compositional MR sequences (for quantification of physical tissue parameters) are currently reserved for scientific research questions. The future integration of artificial intelligence techniques in areas such as image reconstruction (to reduce scan times while maintaining image quality), image analysis (for automated identification of cartilage defects), and image postprocessing (for automated segmentation of cartilage in terms of volume and thickness) will significantly improve the diagnostic workflow and advance the field further.

Glycosaminoglycan-peptide complex: data on the mechanism of action and efficacy in osteoarthritis

The article presents the modern definition of osteoarthritis (OA) not as a degenerative cartilage injury, but as a disease in which abnormal adaptive regenerative processes are activated, including pro-inflammatory pathways of the immune system, based on the clarification of the pathogenesis of the disease. An approach to the separation of various OA phenotypes is described. Various approaches to the tactics of pharmacological treatment of the disease are presented. The possibilities of the glycosaminoglycan-peptide complex to influence the state of chondrocytes and cartilage tissue in various experimental models of induced OA are described. And in the last experimental study, a positive effect of the drug on the clinical manifestations of 2 models of induced OA was demonstrated, a decrease in the concentration of CRP, interleukin 1β was recorded with an increase in the concentration of anti-inflammatory cytokines (interleukins 4 and 10), a significant decrease in the number of leukocytes in the synovial fluid, as well as a decrease in pathological changes in cartilage during histological examination, which it indicates that the drug exerts its effect directly in the tissues of the joint. Clinical studies have confirmed the analgesic and anti-inflammatory activity of the glycosaminoglycan-peptide complex in OA, although not all conducted in the twentieth century, the positive effect on joint pain and joint function was significantly better than placebo. The absence in these years of regulated criteria for inclusion in studies of the effectiveness of pharmacological drugs in OA, the introduction of new methods for assessing pain, function served as a prerequisite for conducting studies of the effectiveness and tolerability of the glycosaminoglycan-peptide complex at the present stage. Multicenter observational studies, which included massive groups of patients with OA of various localization, confirmed the presence of analgesic and anti-inflammatory activity in the drug, manifested during the 1st course of injections, showed that repeated courses of drug administration are necessary to achieve a more pronounced and stable effect. Data on an increase in the effect of combination therapy with diacerein and on the possibility of achieving an effect in patients with previous insufficient efficacy of other slow-acting symptomatic drugs are presented.

Consensus for Statements Regarding a Definition for Spinal Osteoarthritis for Use in Research and Clinical Practice: A Delphi Study.

To determine consensus among an international, multidisciplinary group of experts regarding definitions of spinal osteoarthritis for research and for clinical practice. A 15-member, multidisciplinary steering committee generated 117 statements for a 3-round Delphi study. Experts in back pain and/or osteoarthritis were identified and invited to participate. In round 1, participants could propose additional statements for voting. All statements were rated on a 1-9 Likert scale, and consensus was set at ≥70% of respondents agreeing or disagreeing with the statement and <15% of respondents providing the opposite response. In total, 255 experts from 11 different professional backgrounds were invited. From 173 available experts, 116 consented to participate. In round 1, 103 participants completed the survey, followed by 85 of 111 participants in round 2 (77%) and 87 of 101 participants in round 3 (86%). One-third of participants were from Europe (30%), most were male (58%), one-fifth were physical therapists (21%), and over one-third had been in their profession for 11-20 years (35%). Of 131 statements, consensus was achieved for 71 statements (54%): 53 in agreement (75%) and 18 in disagreement (25%). Although there was consensus for statements for definitions of spinal osteoarthritis that were analogous to definitions of osteoarthritis in appendicular joints, a future definition still needs refinement. Importantly, this Delphi highlighted that a future definition should be considered across a spectrum of structural changes and patient symptoms and expressed on a progressive scale.

Early knee OA definition-what do we know at this stage? An imaging perspective.

While criteria for early-stage knee osteoarthritis (OA) in a primary care setting have been proposed, the role of imaging has been limited to radiography using the standard Kellgren-Lawrence classification. Standardized imaging and interpretation are critical with radiographs, yet studies have also shown that even early stages of radiographic OA already demonstrate advanced damage to knee joint tissues such as cartilage, menisci, and bone marrow. Morphological magnetic resonance imaging (MRI) shows degenerative damage earlier than radiographs and definitions for OA using MRI have been published though no accepted definition of early OA based on MRI is currently available. The clinical significance of structural abnormalities has also not been well defined, and the differentiation between normal aging and structural OA development remains a challenge. Compositional MRI of cartilage provides information on biochemical, degenerative changes within the cartilage matrix before cartilage defects occur and when cartilage damage is potentially reversible. Studies have shown that cartilage composition can predict cartilage loss and radiographic OA. However, while this technology is most promising for characterizing early OA it has currently limited clinical application. Better standardization of compositional MRI is required, which is currently work in progress. Finally, there has been renewed interest in computed tomography (CT) for assessing early knee OA as new techniques such as weight bearing and spectral CT are available, which may provide information on joint loading, cartilage, and bone and potentially have a role in better characterizing early OA. In conclusion, while imaging may have a limited role in diagnosing early OA in a primary care setting, there are advanced imaging technologies available, which detect early degeneration and may thus significantly alter management as new therapeutic modalities evolve.

PREVALENCE OF STRUCTURAL LESIONS AND OSTEOARTHRITIS IN FEMOROTIBIAL JOINTS OF ASYMPTOMATIC PARTICIPANTS FROM THE LAUSANNE KNEE STUDY

Structural lesions of the cartilage, menisci, and bone are prevalent on knee MRIs in the asymptomatic population. The presence of such lesions may lead to the diagnosis of osteoarthritis (OA) according to imaging criteria. The prevalence of OA at imaging may depend on the definition criteria used (radiographic vs. MRI criteria). 1) To determine the prevalence of structural lesions of the femorotibial joint in two groups of young and older asymptomatic participants with healthy knees from the Lausanne Knee Study (LKS). 2) To determine the prevalence of OA in that population using radiographic and MRI definitions of OA. Asymptomatic volunteers were prospectively enrolled in this IRB-approved HIPPA-compliant study. Inclusion criteria: age between18-35 or 45-70 years, no knee symptoms in the past 12 months, no history of severe lower limb injury requiring surgery or not, no impairment that might affect gait, BMI≤30. All participants (n=430, 47.8 years ±16.17 (SD), range 18-70 y, 192 (44.6%) male) underwent a clinical evaluation, including KOOS and WOMAC scores to evaluate pain and knee function, radiographic imaging (weight-bearing Schuss and lateral radiographs of both knees, full spine and lower extremity weight-bearing low dose 3D biplanar radiographs (EOS)), and 3T MRI of a randomly selected knee. MRI protocol included 2D fat-suppressed FSE IW images (sagittal, coronal, and transverse planes), isotropic 3D DESS, high-resolution 3D T1. One musculoskeletal radiologist with 6 years of experience graded radiographs (KL score) and knee MRIs for all structural lesions included in the MOAKS criteria. For this study, only femorotibial compartments will be presented. OA was defined as a KL score≥2 at radiography, or using the criteria proposed by Hunter et al (2011) at MRI. There were 137 participants in the young (Y) (26.2y±4.7; 65 male (47.4%)) and 293 in the older (O) group (57.9y±7.23; 127 male (43.3%)). Participants had no knee pain or functional impairment (average KOOS 97.6±2.51 vs 97.2±3.78 in Y vs O group (p=0.26); average WOMAC 97.8±5.48 vs 96.7±8.23 in Y vs O group (p=0.16)). Structural lesions were highly prevalent in the femorotibial joints (decreasing order of prevalence): 190 (44.2%) cartilage damage (7 vs 183 in Y vs. O, p<10−5), 132 (30.7%) BML (5 vs 127 in Y vs. O, p<10−5), 111 (25.8%) meniscal damage (2 vs 109/ in Y vs. O, p<10−5), 110 (25.6%) had peri-articular cysts (13 vs 97 in Y vs. O, p<10−5), 104 (24.2%) participants had osteophytes (3 vs 101/ in Y vs. O, p<10−5), 68 (15.8%) Hoffa synovitis (3 vs 65 in Y vs. O, p<10−5), 38 (8.8%) synovitis/effusion (3 vs 35 in Y vs. O, p<10−3), and 17 (4%) had loose bodies (1 vs 16 in Y vs. O, p=0.019). 76 (17.7%) participants (1 young) had radiographic OA (60 KL2; 16 KL3; 0 KL4), while 24 (5.6%) participants (all from the older group) had femorotibial OA based on MRI criteria, 198 (46%) had normal MRI, and 208 (48.4%) had structural lesions of variable severity that did not fulfill MRI criteria of OA. In a cohort of 430 asymptomatic volunteers with clinically healthy knees, structural lesions were present in up to 54% of femorotibial joints, with their prevalence increasing with age. The prevalence of OA at imaging in healthy knees may be high and depends on the criteria used (prevalence of 5.6% vs. 17.7% when using MRI vs. radiographic criteria).

Magnetic resonance imaging as a structural refinement to the American College of Rheumathology clinical classification criteria for knee osteoarthritis

To evaluate if fulfilment of the definition of osteoarthritis (OA) based on the American College of Rheumatology (ACR) clinical criteria corresponds to pathological knee findings evaluated by magnetic resonance imaging (MRI). To evaluate if any such criteria is associated with a specific MRI pattern. Forty-six consecutive patients aged 50 years or more referred by their general practitioners (GPs) to a radiology department because of non-traumatic knee pain underwent MRI using a dedicated low field (0.2 T) machine. MRI results were compared against the ACR criteria for knee OA. Patients with knee pain fulfilling the ACR criteria showed more severe synovial fluid effusion (OR 6.2, 95% CI 2.02 to 19.1), cartilage lesions in the medial area (OR 2.4, 95% CI 1.2 to 5) and higher mean number of osteophytes (OR 2.3, 95% CI 1.1 to 4.5). The association between single criteria and MRI features was more difficult to establish. Nonetheless, crepitus at joint movement was associated with synovial fluid effusion (p=0.02); bone enlargement was more frequent in patients with lesions of the posterior cruciate ligament (p=0.0001); no palpable warmth was associated with cartilage lesions (p=0.02), and morning stiffness shorter than 30 minutes was associated with the surface of bone edema (p=0.02). The ACR clinical criteria identify patients showing the most important features of OA. The association between individual clinical ACR criteria and OA pathology depicted by MRI may be difficult to explain on the basis of anatomical changes and needs further evaluation.

Evaluation of osteoarthritic features in peripheral joints by ultrasound imaging: A systematic review

The role of ultrasound imaging for osteoarthritis (OA) diagnosis in peripheral joints has not been clearly defined. To further understand this role, the objectives of this study were to determine how structural and inflammatory OA features in peripheral joints are assessed, defined and graded by ultrasound imaging. MEDLINE, CINAHL, Cochrane and SPORTDiscus databases were systematically searched in March 2021. To be eligible, studies needed to (1) include participants with peripheral joint OA, and (2) use grey scale and/or power Doppler ultrasound imaging to assess one or more ultrasound features in peripheral joints of the hands and feet. Methodological quality of all included studies was assessed using the Critical Appraisal Skills Program tool [1]. A total of 159 citations were identified for screening. Thirty-two articles were included for final analysis and were of good methodological quality. Thirty articles evaluated ultrasound features of hand OA and two assessed ultrasound OA features in the foot. There were inconsistencies between studies in terms of what ultrasound features were assessed, how these features were defined and what grading system was applied to determine degree of osteoarthritic change. The review found inconsistencies in the definition of synovial pathology. Consequently, it is unclear whether synovial pathology is best represented as separate entities or combined as a single domain, termed “synovitis”. How OA ultrasound features were defined and graded has largely been extrapolated from recommendations originally constructed for populations with rheumatoid arthritis. Given the prognostic value of synovitis for OA progression and that inflammation associated with OA is fundamentally different from that in rheumatoid arthritis [2, 3], the validity of applying definitions, grading systems and atlases originally developed for rheumatoid arthritis needs consideration. This review strengthens the case for further refinement and validation of OA definitions, grading systems and ultrasound atlases specific to peripheral joints.

Osteoarthritis: New Insight on Its Pathophysiology.

Understanding of the basis of osteoarthritis (OA) has seen some interesting advancements in recent years. It has been observed that cartilage degeneration is preceded by subchondral bone lesions, suggesting a key role of this mechanism within the pathogenesis and progression of OA, as well as the formation of ectopic bone and osteophytes. Moreover, low-grade, chronic inflammation of the synovial lining has gained a central role in the definition of OA physiopathology, and central immunological mechanisms, innate but also adaptive, are now considered crucial in driving inflammation and tissue destruction. In addition, the role of neuroinflammation and central sensitization mechanisms as underlying causes of pain chronicity has been characterized. This has led to a renewed definition of OA, which is now intended as a complex multifactorial joint pathology caused by inflammatory and metabolic factors underlying joint damage. Since this evidence can directly affect the definition of the correct therapeutic approach to OA, an improved understanding of these pathophysiological mechanisms is fundamental. To this aim, this review provides an overview of the most updated evidence on OA pathogenesis; it presents the most recent insights on the pathophysiology of OA, describing the interplay between immunological and biochemical mechanisms proposed to drive inflammation and tissue destruction, as well as central sensitization mechanisms. Moreover, although the therapeutic implications consequent to the renewed definition of OA are beyond this review scope, some suggestions for intervention have been addressed.

Risk Assessment for Hip and Knee Osteoarthritis Using Polygenic Risk Scores.

ObjectivePolygenic risk scores (PRS) allow risk stratification using common single‐nucleotide polymorphisms (SNPs), and clinical applications are currently explored for several diseases. This study was undertaken to assess the risk of hip and knee osteoarthritis (OA) using PRS.MethodsWe analyzed 12,732 individuals from a population‐based cohort from the Rotterdam Study (n = 11,496), a clinical cohort (Cohort Hip and Cohort Knee [CHECK] study; n = 908), and a high‐risk cohort of overweight women (Prevention of Knee OA in Overweight Females [PROOF] study; n = 328), for the association of the PRS with prevalence/incidence of radiographic OA, of clinical OA, and of total hip replacement (THR) or total knee replacement (TKR). The hip PRS and knee PRS contained 44 and 24 independent SNPs, respectively, and were derived from a recent genome‐wide association study meta‐analysis. Standardized PRS (with Z transformation) were used in all analyses.ResultsWe found a stronger association of the PRS for clinically defined OA compared to radiographic OA phenotypes, and we observed the highest PRS risk stratification for TKR/THR. The odds ratio (OR) per SD was 1.3 for incident THR (95% confidence interval [95% CI] 1.1–1.5) and 1.6 (95% CI 1.3–1.9) for incident TKR in the Rotterdam Study. The knee PRS was associated with incident clinical knee OA in the CHECK study (OR 1.3 [95% CI 1.1–1.5]), but not for the PROOF study (OR 1.2 [95% CI 0.8–1.7]). The OR for OA increased gradually across the PRS distribution, up to 2.1 (95% CI 1.4–3.2) for individuals with the 10% highest PRS compared to the middle 50% of the PRS distribution.ConclusionOur findings validated the association of PRS across OA definitions. Since OA is becoming frequent and primary prevention is not commonly applicable, PRS‐based risk assessment could play a role in OA prevention. However, the utility of PRS is dependent on the setting. Further studies are needed to test the integration of genetic risk assessment in diverse health care settings.

Recreational Physical Activity and Risk of Incident Knee Osteoarthritis: An International Meta-Analysis of Individual Participant-Level Data.

The effect of physical activity on the risk of developing knee osteoarthritis (OA) is unclear. We undertook this study to examine the relationship between recreational physical activity and incident knee OA outcomes using comparable physical activity and OA definitions. Data were acquired from 6 global, community-based cohorts of participants with and those without knee OA. Eligible participants had no evidence of knee OA or rheumatoid arthritis at baseline. Participants were followed up for 5-12 years for incident outcomes including the following: 1) radiographic knee OA (Kellgren-Lawrence [K/L] grade ≥2), 2) painful radiographic knee OA (radiographic OA with knee pain), and 3) OA-related knee pain. Self-reported recreational physical activity included sports and walking/cycling activities and was quantified at baseline as metabolic equivalents of task (METs) in days per week. Risk ratios (RRs) were calculated and pooled using individual participant data meta-analysis. Secondary analysis assessed the association between physical activity, defined as time (hours per week) spent in recreational physical activity and incident knee OA outcomes. Based on a total of 5,065 participants, pooled RR estimates for the association of MET days per week with painful radiographic OA (RR 1.02 [95% confidence interval (95% CI) 0.93-1.12]), radiographic OA (RR 1.00 [95% CI 0.94-1.07]), and OA-related knee pain (RR 1.00 [95% CI 0.96-1.04]) were not significant. Similarly, the analysis of hours per week spent in physical activity also showed no significant associations with all outcomes. Our findings suggest that whole-body, physiologic energy expenditure during recreational activities and time spent in physical activity were not associated with incident knee OA outcomes.

Prevalence of multimorbid degenerative lumbar spinal stenosis with knee or hip osteoarthritis: a systematic review and meta-analysis

BackgroundMusculoskeletal multimorbidity is common and coexisting lumbar spinal stenosis (LSS) with knee or hip osteoarthritis (OA) has been reported. The aim of this review was to report the prevalence of multimorbid degenerative LSS with knee or hip OA based on clinical and/or imaging case definitions.MethodsLiterature searches were performed in MEDLINE, EMBASE, CENTRAL, and CINAHL up to May 2021. Studies involving adults with cross-sectional data to estimate the prevalence of co-occurring LSS with knee or hip OA were included. Study selection, data extraction, and risk of bias assessment were performed independently by two reviewers. Results were stratified according to index and comorbid condition, and by case definitions (imaging, clinical, and combined).ResultsTen studies from five countries out of 3891 citations met the inclusion criteria. Sample sizes ranged from 44 to 2,857,999 (median 230) and the mean age in the included studies range from 61 to 73 years (median 66 years). All studies were from secondary care or mixed settings. Nine studies used a combined definition of LSS and one used a clinical definition. Imaging, clinical, and combined case definitions of knee and hip OA were used. The prevalence of multimorbid LSS and knee or hip OA ranged from 0 to 54%, depending on the specified index condition and case definitions used. Six studies each provided prevalence data for index LSS and comorbid knee OA (prevalence range: 5 to 41%) and comorbid hip OA (prevalence range: 2 to 35%). Two studies provided prevalence data for index knee OA and comorbid LSS (prevalence range 17 to 54%). No studies reporting prevalence data for index hip OA and comorbid LSS were found. Few studies used comparable case definitions and all but one study were rated as high risk of bias.ConclusionsThere is evidence that multimorbid LSS with knee or hip OA occurs in people (0 to 54%), although results are based on studies with high risk of bias and surgical populations. Variability in LSS and OA case definitions limit the comparability of studies and prevalence estimates should therefore be interpreted with caution.Review registrationPROSPERO (CRD42020177759).

Systematic Review of the Evolution of Health-Economic Evaluation Models of Osteoarthritis.

To comprehensively synthesize the evolution of health-economic evaluation models (HEEMs) of all osteoarthritis (OA) interventions, including preventions, core treatments, adjunct nonpharmacologic interventions, pharmacologic interventions, and surgical treatments. The literature was searched within health-economic/biomedical databases. Data extracted included OA type, population characteristics, model setting/type/events, study perspective, and comparators; the reporting quality of the studies was also assessed. The review protocol was registered at the International Prospective Register of Systematic Reviews (CRD42018092937). Eighty-eight studies were included. Pharmacologic and surgical interventions were the focus in 51% and 44% of studies, respectively. Twenty-four studies adopted a societal perspective (with increasing popularity after 2013), but most (63%) did not include indirect costs. Quality-adjusted life years was the most popular outcome measure since 2008. Markov models were used by 62% of studies, with increasing popularity since 2008. Until 2010, most studies used short-to-medium time horizons; subsequently, a lifetime horizon became popular. A total of 86% of studies reported discount rates (predominantly between 3% and 5%). Studies published after 2002 had a better coverage of OA-related adverse events (AEs). Reporting quality significantly improved after 2001. OA HEEMs have evolved and improved substantially over time, with the focus shifting from short-to-medium-term pharmacologic decision-tree models to surgical-focused lifetime Markov models. Indirect costs of OA are frequently not considered, despite using a societal perspective. There was a lack of reporting sensitivity of model outcome to input parameters, including discount rate, OA definition, and population parameters. While the coverage of OA-related AEs has improved over time, it is still not comprehensive.

The clinical significance of and prospects for the use of biopolymer-based microheterogeneous collagen-containing injectable hydrogel in the therapy of osteoarthritis

The paper gives the current definition of osteoarthritis (OA), which reflects the pathogenetic and clinical characteristics of this disease, as well as general principles for choosing an OA treatment. It describes the effect of glucosamine and chondroitin on the key pathogenetic mechanisms of OA. It is noted that one of the promising areas of therapy for OA is the intra-articular administration of biopolymer-based hydrogels that provide not only an anti-inflammatory, but also regenerative effect that has been experimentally confirmed during their injection into the tendon sheaths. There are data on the efficacy and safety of the Russian drug Sphero®gel, a biopolymer-based microheterogeneous collagen-containing hydrogel that belongs to a class of multicomponent biopolymer-based extracellular matrix mimetics. It consists of the cross-linked farm animal tissue-derived collagen microparticles placed in the gel base. The gel is not only a structural base for collagen microparticles; it also has its own therapeutic potential, since it is structurally similar to the natural extracellular matrix. The drug contains collagen, biologically active components of the extracellular matrix, such as proteoglycans, glycoproteins, uronic acids, growth factors, monosaccharides, and chondroitin sulfate. Extended-release symptomatic agents, Sphero®gel among them, are currently recommended for the treatment of OA. Application of Sphero®gel contributes to increased joint mobility and reduced pain, which allows the limited use of nonsteroidal anti-inflammatory drugs that cause adverse reactions, especially in the presence of comorbid diseases.

Serum fatty acid chain length associates with prevalent symptomatic end-stage osteoarthritis, independent of BMI

Higher body mass index (BMI) is associated with osteoarthritis (OA) in both weight-bearing and non-weight-bearing joints, suggesting a link between OA and poor metabolic health beyond mechanical loading. This risk may be influenced by systemic factors accompanying BMI. Fluctuations in concentrations of metabolites may mark or even contribute to development of OA. This study explores the association of metabolites with radiographic knee/hip OA prevalence and progression. A 1H-NMR-metabolomics assay was performed on plasma samples of 1564 cases for prevalent OA and 2,125 controls collected from the Rotterdam Study, CHECK, GARP/NORREF and LUMC-arthroplasty cohorts. OA prevalence and 5 to 10 year progression was assessed by means of Kellgren-Lawrence (KL) score and the OARSI-atlas. End-stage knee/hip OA (TJA) was defined as indication for arthroplasty surgery. Controls did not have OA at baseline or follow-up. Principal component analysis of 227 metabolites demonstrated 23 factors, of which 19 remained interpretable after quality-control. Associations of factor scores with OA definitions were investigated with logistic regression. Fatty acids chain length (FALen), which was included in two factors which associated with TJA, was individually associated with both overall OA as well as TJA. Increased Fatty Acid chain Length is associated with OA.

Comparison of radiographic and MRI osteoarthritis definitions and their combination for prediction of tibial cartilage loss, knee symptoms and total knee replacement: a longitudinal study

To describe the value of radiographic- and magnetic resonance imaging (MRI)-defined tibiofemoral osteoarthritis (ROA and MRI-OA, respectively) and in combination for predicting tibial cartilage loss, knee pain and disability and total knee replacement (TKR) in a population-based cohort. A radiograph and 1.5T MRI of the right knee was performed. ROA and MRI-OA at baseline were defined according to the Osteoarthritis Research Society International atlas and a published Delphi exercise, respectively. Tibial cartilage volume was measured over 2.6 and 10.7 years. Knee pain and disability were assessed at baseline, 2.6, 5.1 and 10.7 years. Right-sided TKRs were assessed over 13.5 years. Of 574 participants (mean 62 years, 49% female), 8% had ROA alone, 15% had MRI-OA alone, 13% had both ROA and MRI-OA. Having ROA (vs. no ROA) and MRI-OA (vs. no MRI-OA) predicted greater tibial cartilage loss over 2.6 years (-75.9 and-86.4mm3/year) and higher risk of TKR over 13.5 years (Risk Ratio [RR]: 15.0 and 10.9). Only MRI-OA predicted tibial cartilage loss over 10.7 years (-7.1mm3/year) and only ROA predicted onset and progression of knee symptoms (RR: 1.32-1.88). In participants with both MRI-OA and ROA, tibial cartilage loss was the greatest (over 2.6 years:-116.1mm3/year; over 10.7 years:-11.2mm3/year), and the onset and progression of knee symptoms (RR: 1.75-2.89) and risk of TKR (RR: 50.9) were the highest. The Delphi definition of MRI-OA is not superior to ROA for predicting structural or symptomatic OA progression but, combining MRI-OA and ROA has much stronger predictive validity.

Comparison of radiographic and MRI osteoarthritis definitions and their combination for prediction of tibial cartilage loss, knee symptoms and total knee replacement - a longitudinal study

Purpose: In the absence of a clear definition of osteoarthritis (OA) using magnetic resonance imaging (MRI) features, the Osteoarthritis Research Society International (OARSI) OA Imaging Working Group developed a definition of MRI-defined structural OA (MRI-OA) by incorporating MRI changes using a Delphi approach, but this needs validation. This study aimed to assess whether MRI-OA is superior to the radiographic definition of OA (ROA) by describing their value for predicting tibial cartilage loss, knee pain and disability and total knee replacement (TKR) in a population-based cohort.

Neuromuscular alterations in knee osteoarthritis: a systematic review and meta-analysis

Purpose: Neuromuscular alterations are commonly reported in knee osteoarthritis (OA) patients and neuromuscular training is being suggested as a first-line treatment. It is crucial to completely understand these alterations, including neural, structural and functional changes, to optimize interventions for knee OA patients. The aim of this systematic review was to systematically evaluate and determine the current evidence on the neuromuscular alterations of periarticular muscles in patients with knee OA when compared to age- and sex-matched healthy controls. Methods: We searched five databases (Pubmed, Embase, Web of Science, Scopus, Cochrane Central Register of Controlled Trials) for studies comparing neuromuscular alterations of periarticular muscles (i.e. quadriceps, hamstring, gastrocnemius, soleus, popliteus) in a knee OA population to an age- and sex-matched asymptomatic control group. We did not accept contralateral knee as the control group, as there is evidence of bilateral changes in unilateral disease presence. We only included studies reporting structural severity of the OA patients. Outcomes included normalized isokinetic strength, voluntary activation, cortical and spinal-reflex excitability, muscle morphology, and electromyography. Only moderate- and high-quality studies are included assessed by a modified Downs and Black checklist. We performed meta-analyses with random-effects model, grouping on radiographic OA severity, for outcome measures reported by two or more studies. Level of evidence is decided based on van Tulder et al. (2003). We also created an evidence gap-map to show which outcomes need more research. Results: We identified and included 7 high- and 37 medium-quality studies. One prospective cohort and 43 case-control studies reported data for 1643 OA patients and 1532 healthy controls. OA definitions hugely differed among studies in terms of structural severity. There was a high risk of selection bias in the included studies and blinding was not performed in most (n=40/44). Most studies reported quadriceps or hamstring muscle strength (n=24/44), while neural or structural alterations have been of less interest. Studies generally measured quadriceps (n=43/44) or hamstring muscles (n=23/44), while gastrocnemius (n=10/44), soleus (n=1/44) or popliteus (n=0/44) have been of less interest. Our findings indicated deficits in quadriceps (-0.72 [-0.95, -0.50], I2=72%, moderate evidence) and hamstring strength (-0.51 [-0.69, -0.33], I2=0%, moderate evidence) in knee OA patients. We also found lower quadriceps voluntary activation (-0.58 [-0.92, -0.23], I2=36%, moderate evidence) in knee OA group. No change was seen in quadriceps torque variability (0.43 [-0.60, 1.46], I2=84, limited evidence). Structural changes within the muscle focused on muscle volume and intermuscular fat for quadriceps. Results indicated no change in quadriceps muscle volume (0.10 [-0.03, 0.23], I2=0, strong evidence) but increased quadriceps intermuscular fat volume (0.39 [0.26, 0.52], I2=0, strong evidence) in knee OA population. For muscle activation, patients with knee OA showed increased muscle co-contraction for vastus medialis/medial gastrocnemius (0.88 [0.45, 1.30], I2=0%, moderate evidence) but not for vastus medialis/medial hamstring (0.23 [-0.18, 0.64], I2=0%, moderate evidence) during functional tasks. Conclusions: Our findings indicated that deficits in quadriceps and hamstring muscle strength in concurrence with quadriceps voluntary activation deficits are evident in knee OA patients. The lack of deficits of the quadriceps volume indicates that quadriceps weakness may be the result of neural inhibition more than muscle atrophy. This may support the use of neuromuscular training exercises in knee OA populations to increase neural drive. We also found increased co-contraction levels for vastus medialis and medial gastrocnemius muscles but not for vastus medialis and medial hamstring muscles. This interesting finding indicates that the interaction of quadriceps-gastrocnemius muscles may be more relevant than quadriceps-hamstring muscles in knee OA patients. Co-contractions differences may alter the loading of the knee joint; therefore, future studies optimizing the interventions for these co-contraction alterations in knee OA patients may be beneficial to avoid further degeneration. Despite huge number of studies being published in knee OA research, there are still very low evidence levels and poorly reported outcomes in studies measuring neuromuscular manifestations of the disease. High-quality studies with matched healthy control groups are still needed to understand neuromuscular alterations associated with knee OA. Better definition of OA following current guidelines and clearer participant selection processes are needed in future studies to increase evidence level.