Osteoarthritis Disease Process Research Articles

Omega-3 Supplementation and Its Effects on Osteoarthritis.

Osteoarthritis (OA) is a degenerative joint disease characterized by the destruction of the articular cartilage, resulting in a pro-inflammatory response. The progression of OA is multifactorial and is influenced by the underlying cause of inflammation, which includes but is not limited to trauma, metabolism, biology, comorbidities, and biomechanics. Although articular cartilage is the main tissue affected in osteoarthritis, the chronic inflammatory environment negatively influences the surrounding synovium, ligaments, and subchondral bone, further limiting their functional abilities and enhancing symptoms of OA. Treatment for osteoarthritis remains inconsistent due to the inability to determine the underlying mechanism of disease onset, severity of symptoms, and complicating comorbidities. In recent years, diet and nutritional supplements have gained interest regarding slowing the disease process, prevention, and treatment of OA. This is due to their anti-inflammatory properties, which result in a positive influence on pain, joint mobility, and cartilage formation. More specifically, omega-3 polyunsaturated fatty acids (PUFA) have demonstrated an influential role in the progression of OA, resulting in the reduction of cartilage destruction, inhibition of pro-inflammatory cytokine cascades, and production of oxylipins that promote anti-inflammatory pathways. The present review is focused on the assessment of evidence explaining the inflammatory processes of osteoarthritis and the influence of omega-3 supplementation to modulate the progression of osteoarthritis.

Worse Patient-Reported Outcomes and Spino-Pelvic Parameters After Total Hip Arthroplasty for Rapidly Progressive Osteoarthritis of the Hip Compared to Osteoarthritis: A Propensity-Matched Cohort Study

BackgroundThis study aimed to assess the association between the disease process of hip osteoarthritis and total hip arthroplasty (THA) outcomes; this is a critical issue, as rapid progression has been postulated to be responsible for patient dissatisfaction after THA. MethodsThis retrospective case-control study included 255 patients who underwent THA and completed a mean follow-up duration of 42.1 months (range, 24.0 to 77.0). We classified patients into those who had (n = 26) and did not have (n = 229) rapidly progressive osteoarthritis of the hip (RPOA), defined as a narrowing rate of joint space ≥ 2 mm yearly or a ≥ 50% loss within 12 months, excluding any other cause of a destructive arthropathy. Propensity score-matched cohorts for age, sex, body mass index, and spino-pelvic measures were created, and the outcomes were compared between the 2 groups. ResultsAfter successfully matching RPOA (n = 25) and non-RPOA patients (n = 50), there were significant differences in minimum clinically important difference (P = .009 for European Quality of Life 5-Dimension, and P < .001 for low back pain), patient acceptable symptom state (P = .015 for European Quality of Life 5-Dimension, and P < .001 for Hip Disability and Osteoarthritis Outcome Score Joint Replacement score), patient satisfaction (P = .028), and T1 pelvic angle as an indicator of global sagittal spinal deformity (P = .017). There was a correlation between T1 pelvic angle and low back pain in the RPOA group (R = 0.628, P < .001). ConclusionsPatients who exhibited RPOA before undergoing THA showed worse patient-reported outcomes compared with those who did not have rapid progression. Our study highlights the critical role of the disease process in influencing THA outcomes, advocating for a paradigm shift toward more meticulous preoperative evaluations, including global spinal deformity, standardized diagnostic criteria, and tailored interventions.

3-dimensional bone shape and knee osteoarthritis: What have we learned?

The concept that multiple joint tissues are involved in the osteoarthritis (OA) disease process is now widely accepted. There have been significant and important insights over the past two decades in the understanding of bone as a tissue undergoing pathological changes in OA. The specific bony changes of osteophyte growth and “bone attrition” associated with OA have been recognized for many years with several semi-quantitative radiographic and magnetic resonance imaging (MRI) grading systems designed to capture the magnitude of these changes. Over the past decade, there has been significant and important progress in the quantitative measurement of these changes. Manual methods for measuring bone area from 3D MR images have been improved with automation which offers both superior precision and a more responsive measurement that has been applied in several DMOAD randomized controlled trials. Measurement of true 3D bone shape, as opposed to simple geometric measures such as curvature and length, depends on automated methods of segmentation. In this field, important developments have taken place in the statistical parameterization of shape and the construction of OA vs non-OA shape metrics. Work has demonstrated that bone shape may provide an indication of OA status, may predict future OA onset, and is associated with clinical markers of OA such as pain, function and total joint replacement (TKR). Thus, bone shape may be a useful imaging biomarker for OA.

Glucagon-like peptide-1 receptor agonists as a disease-modifying therapy for knee osteoarthritis mediated by weight loss: findings from the Shanghai Osteoarthritis Cohort

ObjectiveObesity is a risk factor for knee osteoarthritis (KOA) development and progression. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are indicated for type 2 diabetes mellitus (T2DM) and obesity. However, whether KOA...

Update on recent developments in imaging of inflammation in osteoarthritis: a narrative review.

Synovitis is an important component of the osteoarthritis (OA) disease process, particularly regarding the "inflammatory phenotype" of OA. Imaging plays an important role in the assessment of synovitis in OA with MRI and ultrasound being the most deployed imaging modalities. Contrast-enhanced (CE) MRI, particularly dynamic CEMRI (DCEMRI) is the ideal method for synovitis assessment, but for several reasons CEMRI is not commonly performed for OA imaging in general. Effusion-synovitis and Hoffa-synovitis are commonly used as surrogate markers of synovitis on non-contrast-enhanced (NCE) MRI and have been used in many epidemiological observational studies of knee OA. Several semiquantitative MRI scoring systems are available for the evaluation of synovitis in knee OA. Synovitis can be a target tissue for disease-modifying OA drug (DMOAD) clinical trials. Both MRI and ultrasound may be used to determine the eligibility and assess the therapeutic efficacy of DMOAD approaches. Ultrasound is mostly used for evaluation of synovitis in hand OA, while MRI is typically used for larger joints, namely knees and hips. The role of other modalities such as CT (including dual-energy CT) and nuclear medicine imaging (such as positron-emission tomography (PET) and its hybrid imaging) is limited in the context of synovitis assessment in OA. Despite research efforts to develop NCEMRI-based synovitis evaluation methods, these typically underestimate the severity of synovitis compared to CEMRI, and thus more research is needed before we can rely only on NCEMRI.

Delayed Gadolinium-Enhanced Magnetic Resonance Imaging of Cartilage Values in Hips With Bone Marrow Lesions.

Bone marrow lesions (BMLs) are associated with painful and progressive osteoarthritis (OA). Quantitative magnetic resonance imaging (MRI) has been used to study early cartilage degeneration in knees with BML, but similar work has not been done in hips. The purpose of this study was to compare mean delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) relaxation values (T1Gd) in hips with BML to hips without BML in a population-based study. Reduced T1Gd suggests depleted glycosaminoglycan. Our hypothesis was that mean T1Gd is lower in hips with BML compared to hips without BML. Study participants (n=128) were recruited from a cross-sectional population-based study of people ages 20-49 years with and without hip pain. dGEMRIC and proton density (PD)-weighted MRI scans of 1 hip from each participant were used for this analysis. BMLs were identified from PD-weighted fat-suppressed images. We applied a sampling-weighted linear regression model to determine the association of the presence of BMLs with mean cartilage T1Gd (significance: P < 0.05). The model was adjusted for age, sex, body mass index (BMI), hip pain, cam/pincer deformity, and physical activity. Thirty-two (25%) of the 128 participants had at least 1 BML. Subjects with at least 1 BML, compared to those without, had similar weighted characteristics of age, BMI, physical activity levels, and frequency of hip pain. Mean T1Gd was 75.25 msec lower (95% confidence interval -149.69, -0.81; P=0.048) (9%) in the BML compared to the no-BML group. Our results suggest that hips with BMLs are associated with hip cartilage degeneration early in the OA disease process.

Nerve growth factor receptors in equine synovial membranes vary with osteoarthritic disease severity.

Nerve growth factor (NGF) is a neurotrophin that has been implicated in pain signaling, apoptosis, inflammation and proliferation. The resultant effects depend on interaction with two different receptors; tyrosine kinase A (TrkA) and p75NTR . NGF increases in synovial fluid from osteoarthritic joints, and monoclonal antibody therapy is trialed to treat osteoarthritis (OA)-related pain. Investigation of the complex and somewhat contradictory signaling pathways of NGF is conducted in neural research, but has not followed through to orthopaedic studies. The objectives of this study were to compare the expression of NGF receptors and the downstream regulator BAX in synovial membranes from joints in various stages of OA. The horse was used as a model. Synovial membranes were harvested from five healthy horses postmortem and from clinical cases with spontaneous OA undergoing arthroscopic surgery for lameness. Four horses with synovitis without gross cartilage changes, four horses with synovitis and cartilage damage, and four horses with synovitis and intracarpal fractures were included. Samples were investigated by immunohistochemistry and results showed that nuclear staining of TrkA, p75NTR and BAX increases in OA-associated synovitis. TrkA expression increased in early disease stages whereas increases in p75NTR were most prominent in later disease stages with cartilage damage and fibrosis. Clinical significance: Suppression of NGF may result in varied effects depending on different stages of the osteoarthritic disease process.

The Microbiome in Osteoarthritis: a Narrative Review of Recent Human and Animal Model Literature.

The microbiome has recently emerged as a powerful contributor to health and illness in chronic, systemic disorders. Furthermore, new microbiome niches beyond traditional gut locations are frequently being described. Over the past 5years, numerous pivotal studies have demonstrated associations between changes in various microbiome niches and the development of osteoarthritis (OA). Herein, we review the most impactful recent literature, including microbiome associations with disease and the potential therapeutic value of microbiome manipulation. The gut microbiome of human OA patients is enriched in specific bacterial clades, most notably Streptococcus, which correlates with OA pain, Firmicutes, and others. Most studies have focused on knee OA, although one publication demonstrated positive associations with 3 gut microbiome clades in hand OA. OA can be easily distinguished from RA by evaluating differences in oral microbiome composition. Most studies have also demonstrated a reduction in richness of the gut microbiome (alpha diversity) associated with OA. Several studies have identified bacterial signatures within human knee and hip cartilage, synovial fluid, and synovial tissue and have described changes in these patterns occurring with the development of OA. In animal models of OA, high-fat diet-induced obesity has been the most well-studied OA risk factor associated with changes in the microbiome, with numerous bacterial clades changed within the gut microbiome and associated with OA. Also in animal models, various oral supplementations, including dietary fiber, probiotics including Lactobacillus species, and cecal microbiome transplantation have all shown improvements in OA histopathology or cartilage healing. Microbiome changes are strongly associated with the OA disease process and with individual OA risk factors related to both the gut microbiome and the microbial DNA patterns in the joint. Microbiome-directed interventions have the potential to prevent or reduce the progression of OA. Future studies should investigate the mechanistic underpinnings of these microbiome associations and further define the therapeutic potential of microbiome augmentation.

PAIN SEVERITY ACROSS HAND OSTEOARTHRITIS PHENOTYPES BASED ON A BIOPSYCHOSOCIAL APPROACH

Purpose: Hand osteoarthritis (OA) pain is both heterogeneous and multifactorial, involving biological, psychological and social aspects extending beyond the OA disease process. Different phenotypes may have different prognosis and may require different treatments. Hence, the identification of such phenotypes may be clinically important. Currently, no previous studies have examined the presence of different hand OA phenotypes. Therefore, the purpose of this study was to explore classes based on a biopsychosocial framework as possible phenotypes in a hand OA population, and examine whether pain severity differ between the classes.

TOWARDS WEARABLE SENSOR BASED GAIT ANALYSIS IN ROUTINE CLINICAL PRACTICE: ASSOCIATION BETWEEN GAIT KINEMATICS AND PATIENT REPORTED OUTCOMES IN HIP ARTHROPLASTY

Purpose: The potential of gait analysis in understanding the osteoarthritis (OA) disease process and its treatment has long been recognized. Various studies have reported spatiotemporal and kinematic changes in patients with OA based on gait analysis performed in dedicated gait laboratories using reflective markers placed on the skin at predefined anatomical positions captured by high-speed cameras. Recent studies have shown promising data for assessing site specificity of OA gait kinematics with wearable sensors and their association with patient reported outcomes measures (PROMs) in patients with knee or hip OA.

Imaging of Synovial Inflammation in Osteoarthritis, From the AJR Special Series on Inflammation

Synovitis, inflammation of the synovial membrane, is a common manifestation of osteoarthritis (OA) and is recognized to play a role in the complex pathophysiology of OA. Increased recognition of the importance of synovitis in the OA disease process and its potential as a target for treatment has increased the need for noninvasive detection and characterization of synovitis using medical imaging. Numerous imaging methods can assess synovitis involvement in OA with varying sensitivity, specificity, and complexity. This article reviews the role of contrast-enhanced MRI, conventional MRI, novel unenhanced MRI, gray-scale ultrasound (US), and power Doppler US in the assessment of synovitis in patients with OA. The role of imaging in disease evaluation and the challenges of conventional imaging methods are discussed. We also provide an overview of the potential utility of emerging techniques for imaging of early inflammation and molecular inflammatory markers of synovitis, including quantitative MRI, superb microvascular imaging, and PET. The development of therapeutic treatments targeting inflammatory features, particularly in early OA, would greatly increase the importance of these imaging methods for clinical decision-making and evaluation of therapeutic efficacy.

Epigenetic modifications of tumor necrosis factor-alpha in joint cartilage tissue from osteoarthritis patients - CONSORT.

Background:Osteoarthritis (OA) remains one of the most common osteopathy for centuries, which can be attributed to multiple risk factors including mechanical and biochemical ones. More and more studies verified that inflammatory cytokines play important roles in the progression of OA, such as tumor necrosis factor-alpha (TNF-α). In this study, we aimed to investigate the relationship between epigenetic manifestations of TNF-? and the pathogenesis of OA.Methods:Totally, 37 OA patients’ cartilage was collected through the knee joint and 13 samples of articular cartilage as healthy control was collected through traumatic amputation. Real-time PCR, Western blot and ELISA analysis were performed to observe the expression of target genes and proteins in collected samples.Results:Compared with the healthy control group, TNF-? was over-expressing in cartilage which was collected from OA patients. DNA hypomethylation, histone hyperacetylation and histone methylation were observed in the TNF-? promoter in OA compared with normal patients, and we also studied series of enzymes associated with epigenetics. The results showed that by increasing DNA methylation and decreasing histone acetylation in the TNF-? promoter, and TNF-? over-expression in OA cartilage was suppressed, histone methylation has no significant correlation with OA.Conclusion:In conclusion, the changes of epigenetic status regulate TNF-α expression in the cells, which are pivotal to the OA disease process. These results may give us a better understanding of OA and may provide new therapeutic options.

Arthroscopic partial meniscectomy: did it ever work?

ABSTRACT Arthroscopic partial meniscectomy (APM) is one the most common orthopedic surgical procedures. The most common indication for APM is a degenerative meniscal tear (DMT). High-quality evidence suggests that APM does not provide meaningful benefits in patients with DMTs and may even be harmful in the longer term. This narrative review focuses on a fundamental question: considering the history and large number of these surgeries, has APM ever actually worked in patients with DMT? A truly effective treatment needs a valid disease model that would biologically and plausibly explain the perceived treatment benefits. In the case of DMT, effectiveness requires a credible framework for the pain-generating process, which should be influenced by APM. Basic research, pathoanatomy, and clinical evidence gives no support to these frameworks. Moreover, treatment of DMT with an APM does not align with the traditional practice of medicine since DMT is not a reliable diagnosis for knee pain and no evidence-based indication exists that would influence patient prognosis from APM. A plausible and robust explanation supported by both basic research and clinical evidence is that DMTs are part of an osteoarthritic disease process and do not contribute to the symptoms independently or in isolation and that symptoms are not treatable with APM. This is further supported by the fact that APM as an intervention is paradoxical because the extent of procedure and severity of disease are both inversely associated with outcome. We argue that arthroscopic treatment of DMT is largely based on a logical fallacy: post hoc ergo propter hoc.

A Coarse-to-Fine Framework for Automated Knee Bone and Cartilage Segmentation Data from the Osteoarthritis Initiative.

Knee osteoarthritis (OA) is a degenerative joint disease that is prevalent in advancing age. The pathology of OA disease is still unclear, and there are no effective interventions that can completely alter the OA disease process. Magnetic resonance (MR) image evaluation is sensitive for depicting early changes of knee OA, and therefore important for early clinical intervention for relievingthe symptom. Automated cartilage segmentation based on MR images is a vital step in experimental longitudinal studies to follow-up the patients and prospectively define a new quantitative marker from OA progression. In this paper, we develop a deep learning-based coarse-to-fine approach for automated knee bone, cartilage, and meniscus segmentation with high computational efficiency. The proposed method is evaluated using two-fold cross-validation on 507 MR volumes (81,120 slices) with OA from the Osteoarthritis Initiative (OAI)1 dataset. The mean dice similarity coefficients (DSCs) of femoral bone (FB), tibial bone (TB), femoral cartilage (FC), and tibial cartilage (TC) separately are 99.1%, 98.2%, 90.9%, and 85.8%. The time of segmenting each patient is 12s, which is fast enough to be used in clinical practice. Our proposed approach may provide an automated toolkit to help computer-aided quantitative analyses of OA images.

Surgical Induction of Posttraumatic Osteoarthritis in the Mouse.

Given the prevalence and the scope of the personal and societal burden of osteoarthritis (OA), investigators continue to be deeply interested in understanding the pathogenic basis of disease and developing novel disease modifying OA therapies. Because joint trauma/injury is considered a leading predisposing factor in the development of OA, and since posttraumatic OA is one of the most common forms of OA in general, large animal and rodent models of knee injury that accurately recapitulate the OA disease process have become increasingly widespread over the past decade. To enable study in the context of defined genetic backgrounds, investigative teams have developed standardized protocols for injuring the mouse knee that aim to induce a reproducible degenerative process both in terms of severity and temporal pacing of disease progression. The destabilization of the medial meniscus (DMM) is one of the most commonly employed surgical procedure in rodents that reproducibly models posttraumatic OA and allows for the study of disease progression from initiation to end-stage disease. The description provided here sets the stage for both inexperienced and established investigators to employ the DMM procedure, or other similar surgical destabilization methods, to initiate the development of posttraumatic OA in the mouse. Successful application of this method provides a preclinical platform to study the mechanisms driving the pathogenesis of posttraumatic OA and for testing therapeutic strategies to treat it.

Anxiety and Osteoarthritis Disability: Updated Overview and Commentary

Introduction:Osteoarthritis, a widespread highly painful often incapacitating joint disease continues to impose immense personal and societal challenges among adults of all ages, especially among older adults. In the absence of any effective cure or treatment, it has become essential to explore all correlates of this chronic disabling disease, especially those that might be preventable or modifiable. Anxiety, a potentially remediable state of mental distress - found linked to chronically disabling forms of arthritis, in various imperceptible ways, and which may have an immense bearing on the outcomes of osteoarthritis, has not received as much attention in the related literature as other topics, such as surgery.Objective:In line with previous promising work, this narrative review elected to explore the extent to which current researchers in the field are pursuing this topic, and if so, the degree to which prevailing peer-reviewed data sources support an important role for continued research in this realm, and in what regard.Methods:Primarily explored were the key databases housing relevant publications that emerged over Aug 1, 2018-Feb 26, 2020 using the keywordsOsteoarthritisandAnxiety.Using a descriptive approach, the relative progress made over the past five previous years in this regard was assessed, in addition to what joints have been studied and with what frequency, and how the degree of interest compares to other currently researched osteoarthritis themes. The potential for intervening in the osteoarthritis pain cycle by addressing anxiety was also examined.Results:Findings show a high level of current interest in this topic, and that despite the paucity of prospective studies, studies on joints other than the knee and hip joints, some equivocal conclusions, small numbers of anxiety-related studies compared to other topics, and substantive design limitations, it appears that future research in this realm is strongly indicated.Conclusion:This topic if examined further is likely to produce highly advantageous results at all stages of the osteoarthritic disease process and in the context of primary, secondary, as well as tertiary measures to ameliorate osteoarthritis pain and disability.

STAT3 speeds up progression of osteoarthritis through NF‑κB signaling pathway

Osteoarthritis (OA) is the most common motor system disease in the elderly, with a high incidence and a huge social and economic burden. Therefore, it is urgent to study its potential pathogenesis to improve the therapeutic effect of the disease. In this study, we constructed a number of regulator-mediated OA dysfunction modules, and carried out in-depth analysis in order to examine the disease development process. Differential expression analysis, co-expression analysis and enrichment analysis were combined to screen genes related to disease progression. Subsequently, key regulatory factors in the process of OA were identified based on the pivotal regulators that may manipulate important parts of the module subnetwork. A total of 16 OA dysfunction modules were obtained, involving the aggregation of 3,239 module genes. Then, enrichment analysis showed that module genes were significantly involved in apoptosis, inflammation-related functions and signaling pathways. Finally, we revealed a series of regulators, including 842 ncRNA (miR-132-3p, miR-130a-3p and miR-590-3p), 59 transcription factors (NFKB1, RELA and STAT3). We consider that STAT3 is the core transcription factor and promotes the development of OA through the signal of NF-κB. Overall, our results provide biologists and pharmacists with a new way of thinking to reveal the disease process of OA, and provide a wider range of candidate targets for follow-up research.

Fibroblast-like synovial cell production of extra domain A fibronectin associates with inflammation in osteoarthritis

BackgroundThe pathophysiology of osteoarthritis (OA) involves wear and tear, and a state of low-grade inflammation. Tissue repair responses include transforming growth factor beta (TGFβ)-induced myofibroblast production of extracellular matrix. Fibronectins are an essential part of the extracellular matrix, and injection of fibronectin fragments into rabbit joints is a previously established animal model of OA. Fibronectin containing the ED-A domain is currently being used as drug delivery target in the development of anti-inflammatory drugs (e.g. Dekavil).MethodsIn this study, samples of synovial membrane were obtained from patients with knee OA undergoing joint replacement surgery. Immunostaining for ED-A fibronectin and the myofibroblast marker alpha smooth muscle actin (αSMA) was performed on fibroblast-like synovial cells (FLS) and synovial membranes. RAW 264.7 macrophages were incubated with recombinant ED-A fibronectin.ResultsThe staining of ED-A fibronectin in OA FLS was increased by TGFβ but not by TNFα, lipopolysaccharide, or IL-6 (n = 3). ED-A fibronectin co-stained with the myofibroblast marker αSMA in both the OA FLS (n = 3) and in the OA synovial membranes (n = 8). ED-A fibronectin staining was associated with both number of lining layer cells (rho = 0.85 and p = 0.011) and sublining cells (rho = 0.88 and p = 0.007) in the OA synovium (n = 8), and co-distributed with TNFα (n = 5). Recombinant ED-A fibronectin increased the production of TNFα by RAW 264.7 macrophages (n = 3).ConclusionsThe disease process in OA shares features with the chronic wound healing response. Our findings support utilizing ED-A fibronectin for drug delivery or therapeutic targeting to reduce pro-inflammatory responses in OA.

Understanding the role of diabetes in the osteoarthritis disease and treatment process: a study protocol for the Swedish Osteoarthritis and Diabetes (SOAD) cohort

IntroductionOsteoarthritis (OA) is the most common form of arthritis and a leading cause of disability worldwide. Metabolic comorbidities such as type II diabetes occur with a higher rate in people...

Osteoartrozda yeni tedavi yöntemleri

Osteoartroz (OA) en yaygın artrit şeklidir. OA'da klinik çalışmaların sunduğu birçok zorluğa rağmen, hastalık patogenezi, hastalık süreci ve ağrının tedavisinin yanı sıra altta yatan hastalığın tedavisinde birçok yeni farmakolojik tedaviler ve klinik araştırmalar vardır. Yeni farmakolojik ajanlar ile klinikte OA'da semptomların ve hastalık sürecinin iyileştirilmesine yönelik fırsatlar ufukta görünmektedir.