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JAMA Feb 2021Osteoarthritis (OA) is the most common joint disease, affecting an estimated more than 240 million people worldwide, including an estimated more than 32 million in the... (Review)
Review
IMPORTANCE
Osteoarthritis (OA) is the most common joint disease, affecting an estimated more than 240 million people worldwide, including an estimated more than 32 million in the US. Osteoarthritis is the most frequent reason for activity limitation in adults. This Review focuses on hip and knee OA.
OBSERVATIONS
Osteoarthritis can involve almost any joint but typically affects the hands, knees, hips, and feet. It is characterized by pathologic changes in cartilage, bone, synovium, ligament, muscle, and periarticular fat, leading to joint dysfunction, pain, stiffness, functional limitation, and loss of valued activities, such as walking for exercise and dancing. Risk factors include age (33% of individuals older than 75 years have symptomatic and radiographic knee OA), female sex, obesity, genetics, and major joint injury. Persons with OA have more comorbidities and are more sedentary than those without OA. The reduced physical activity leads to a 20% higher age-adjusted mortality. Several physical examination findings are useful diagnostically, including bony enlargement in knee OA and pain elicited with internal hip rotation in hip OA. Radiographic indicators include marginal osteophytes and joint space narrowing. The cornerstones of OA management include exercises, weight loss if appropriate, and education-complemented by topical or oral nonsteroidal anti-inflammatory drugs (NSAIDs) in those without contraindications. Intra-articular steroid injections provide short-term pain relief and duloxetine has demonstrated efficacy. Opiates should be avoided. Clinical trials have shown promising results for compounds that arrest structural progression (eg, cathepsin K inhibitors, Wnt inhibitors, anabolic growth factors) or reduce OA pain (eg, nerve growth factor inhibitors). Persons with advanced symptoms and structural damage are candidates for total joint replacement. Racial and ethnic disparities persist in the use and outcomes of joint replacement.
CONCLUSIONS AND RELEVANCE
Hip and knee OA are highly prevalent and disabling. Education, exercise and weight loss are cornerstones of management, complemented by NSAIDs (for patients who are candidates), corticosteroid injections, and several adjunctive medications. For persons with advanced symptoms and structural damage, total joint replacement effectively relieves pain.
Topics: Adrenal Cortex Hormones; Anti-Inflammatory Agents, Non-Steroidal; Arthroplasty, Replacement; Disease Progression; Exercise; Hip Prosthesis; Humans; Injections, Intra-Articular; Knee Prosthesis; Magnetic Resonance Imaging; Osteoarthritis, Hip; Osteoarthritis, Knee; Weight Loss
PubMed: 33560326
DOI: 10.1001/jama.2020.22171 -
International Journal of Molecular... Aug 2021Osteoarthritis is a common cause of disability worldwide. Although commonly referred to as a disease of the joint cartilage, osteoarthritis affects all joint tissues... (Review)
Review
Osteoarthritis is a common cause of disability worldwide. Although commonly referred to as a disease of the joint cartilage, osteoarthritis affects all joint tissues equally. The pathogenesis of this degenerative process is not completely understood; however, a low-grade inflammation leading to an imbalance between anabolic and katabolic processes is a well-established factor. The complex network of cytokines regulating these processes and cell communication has a central role in the development and progression of osteoarthritis. Concentrations of both proinflammatory and anti-inflammatory cytokines were found to be altered depending on the osteoarthritis stage and activity. In this review, we analyzed individual cytokines involved in the immune processes with an emphasis on their function in osteoarthritis.
Topics: Animals; Biomarkers; Chemokines; Cytokines; Disease Susceptibility; Humans; Inflammation Mediators; Osteoarthritis
PubMed: 34502117
DOI: 10.3390/ijms22179208 -
Osteoarthritis and Cartilage Feb 2022This year in review on osteoarthritis biology summarizes a series of research articles published between the 2020 and 2021 Osteoarthritis Research Society International... (Review)
Review
This year in review on osteoarthritis biology summarizes a series of research articles published between the 2020 and 2021 Osteoarthritis Research Society International (OARSI) World Congress. Research hightlights were selected and discussed based on the new discoveries of OA's cellular molecular mechanism, anatomical signatures, potential therapeutic targets, and regenerative therapy. The recently developed potential therapeutic targets are summarized, and the research focuses on TGFβ and WNT signaling in joint tissue homeostasis, joint aging and the dynamic of synolytics in OA joint, and the roles of TRP2, LDHA, OSCAR in cartilage homeostasis and OA joints are highlighted. Subsquencially, new anatomical structures and OA features are introduced, such as synovitis-induced venous portal circulation, horiozontal fissures between cartilage and subchondral bone, the cellular derivation of osteophytes formation, OA subtypes, and subchondral remodeling and pain biology. Then, research on the possibility of tissue regeneration in OA joints are discussed; skeletal stem cells in OA cartilage regeneration, and preclinical results of regenerative therapy for meniscus tear and osteochondral tissue morphoghesis are included. At last, the clinical evidence of the importance of delivery site of bone marrow stem cells for OA treatment is discussed. These findings represent advances in our understanding of OA pathophysiology.
Topics: Humans; Osteoarthritis
PubMed: 34801671
DOI: 10.1016/j.joca.2021.11.009 -
Signal Transduction and Targeted Therapy Feb 2023Osteoarthritis (OA) is a chronic degenerative joint disorder that leads to disability and affects more than 500 million population worldwide. OA was believed to be... (Review)
Review
Osteoarthritis (OA) is a chronic degenerative joint disorder that leads to disability and affects more than 500 million population worldwide. OA was believed to be caused by the wearing and tearing of articular cartilage, but it is now more commonly referred to as a chronic whole-joint disorder that is initiated with biochemical and cellular alterations in the synovial joint tissues, which leads to the histological and structural changes of the joint and ends up with the whole tissue dysfunction. Currently, there is no cure for OA, partly due to a lack of comprehensive understanding of the pathological mechanism of the initiation and progression of the disease. Therefore, a better understanding of pathological signaling pathways and key molecules involved in OA pathogenesis is crucial for therapeutic target design and drug development. In this review, we first summarize the epidemiology of OA, including its prevalence, incidence and burdens, and OA risk factors. We then focus on the roles and regulation of the pathological signaling pathways, such as Wnt/β-catenin, NF-κB, focal adhesion, HIFs, TGFβ/ΒΜP and FGF signaling pathways, and key regulators AMPK, mTOR, and RUNX2 in the onset and development of OA. In addition, the roles of factors associated with OA, including MMPs, ADAMTS/ADAMs, and PRG4, are discussed in detail. Finally, we provide updates on the current clinical therapies and clinical trials of biological treatments and drugs for OA. Research advances in basic knowledge of articular cartilage biology and OA pathogenesis will have a significant impact and translational value in developing OA therapeutic strategies.
Topics: Humans; Osteoarthritis; Signal Transduction; Cartilage, Articular; NF-kappa B; Transforming Growth Factor beta
PubMed: 36737426
DOI: 10.1038/s41392-023-01330-w -
Osteoarthritis and Cartilage Jan 2022Hip and knee osteoarthritis (OA) are leading causes of global disability. Most research to date has focused on the knee, with results often extrapolated to the hip, and... (Comparative Study)
Comparative Study Review
Hip and knee osteoarthritis (OA) are leading causes of global disability. Most research to date has focused on the knee, with results often extrapolated to the hip, and this extends to treatment recommendations in clinical guidelines. Extrapolating results from research on knee OA may limit our understanding of disease characteristics specific to hip OA, thereby constraining development and implementation of effective treatments. This review highlights differences between hip and knee OA with respect to prevalence, prognosis, epigenetics, pathophysiology, anatomical and biomechanical factors, clinical presentation, pain and non-surgical treatment recommendations and management.
Topics: Humans; Osteoarthritis, Hip; Osteoarthritis, Knee; Prognosis
PubMed: 34600121
DOI: 10.1016/j.joca.2021.09.010 -
Ugeskrift For Laeger Oct 2020Osteoarthritis (OA) is defined by clinical symptoms and radiological signs. Cartilage is crucial in the development, but all tissue components in and around the joint... (Review)
Review
Osteoarthritis (OA) is defined by clinical symptoms and radiological signs. Cartilage is crucial in the development, but all tissue components in and around the joint are affected by the disease. OA aetiopathogenesis is multifactorial and may be primary (idiopathic) or secondary, with an influence of heritable factors. Contributing to OA development are age, joint trauma, other joint diseases, and overweight/obesity. The latter is of special interest being modifiable, and weight loss has proven very effective on symptoms of OA. Over the course of OA, inflammatory flares may be experienced, some associated with crystal formation in the joint, which opens for possible treatments, as argued in this review.
Topics: Humans; Obesity; Osteoarthritis; Overweight; Radiography; Weight Loss
PubMed: 33046193
DOI: No ID Found -
Frontiers in Immunology 2022Obesity remains the most important risk factor for the incidence and progression of osteoarthritis (OA). The leading cause of OA was believed to be overloading the... (Review)
Review
Obesity remains the most important risk factor for the incidence and progression of osteoarthritis (OA). The leading cause of OA was believed to be overloading the joints due to excess weight which in turn leads to the destruction of articular cartilage. However, recent studies have proved otherwise, various other factors like adipose deposition, insulin resistance, and especially the improper coordination of innate and adaptive immune responses may lead to the initiation and progression of obesity-associated OA. It is becoming increasingly evident that multiple inflammatory cells are recruited into the synovial joint that serves an important role in pathological changes in the synovial joint. Polarization of macrophages and macrophage-produced mediators are extensively studied and linked to the inflammatory and destructive responses in the OA synovium and cartilage. However, the role of other major innate immune cells such as neutrophils, eosinophils, and dendritic cells in the pathogenesis of OA has not been fully evaluated. Although cells of the adaptive immune system contribute to the pathogenesis of obesity-induced OA is still under exploration, a quantity of literature indicates OA synovium has an enriched population of T cells and B cells compared with healthy control. The interplay between a variety of immune cells and other cells that reside in the articular joints may constitute a vicious cycle, leading to pathological changes of the articular joint in obese individuals. This review addresses obesity and the role of all the immune cells that are involved in OA and summarised animal studies and human trials and knowledge gaps between the studies have been highlighted. The review also touches base on the interventions currently in clinical trials, different stages of the testing, and their shortcomings are also discussed to understand the future direction which could help in understanding the multifactorial aspects of OA where inflammation has a significant function.
Topics: Animals; Humans; Inflammation; Macrophages; Obesity; Osteoarthritis; Synovial Membrane
PubMed: 35860250
DOI: 10.3389/fimmu.2022.907750 -
Arthritis Research & Therapy Mar 2020Post-traumatic osteoarthritis (PTOA) develops after joint injury. Specifically, patients with anterior cruciate ligament (ACL) injury have a high risk of developing... (Review)
Review
Post-traumatic osteoarthritis (PTOA) develops after joint injury. Specifically, patients with anterior cruciate ligament (ACL) injury have a high risk of developing PTOA. In this review, we outline the incidence of ACL injury that progresses to PTOA, analyze the role of ACL reconstruction in preventing PTOA, suggest possible mechanisms thought to be responsible for PTOA, evaluate current diagnostic methods for detecting early OA, and discuss potential interventions to combat PTOA. We also identify important directions for future research. Although much work has been done, the incidence of PTOA among patients with a history of ACL injury remains high due to the complexity of ACL injury progression to PTOA, the lack of sensitive and easily accessible diagnostic methods to detect OA development, and the limitations of current treatments. A number of factors are thought to be involved in the underlying mechanism, including structural factors, biological factors, mechanical factors, and neuromuscular factor. Since there is a clear "start point" for PTOA, early detection and intervention is of great importance. Currently, imaging modalities and specific biomarkers allow early detection of PTOA. However, none of them is both sensitive and easily accessible. After ACL injury, many patients undergo surgical reconstruction of ACL to restore joint stability and prevent excessive loading. However, convincing evidence is still lacking for the superiority of ACL-R to conservative management in term of the incidence of PTOA. As for non-surgical treatment such as anti-cytokine and chemokine interventions, most of them are investigated in animal studies and have not been applied to humans. A complete understanding of mechanisms to stratify the patients into different subgroups on the basis of risk factors is critical. And the improvement of standardized and quantitative assessment techniques is necessary to guide intervention. Moreover, treatments targeted toward different pathogenic pathways may be crucial to the management of PTOA in the future.
Topics: Animals; Anterior Cruciate Ligament Injuries; Anterior Cruciate Ligament Reconstruction; Biomarkers; Disease Models, Animal; Humans; Osteoarthritis; Osteoarthritis, Knee
PubMed: 32209130
DOI: 10.1186/s13075-020-02156-5 -
Arthritis & Rheumatology (Hoboken, N.J.) Feb 2020To develop an evidence-based guideline for the comprehensive management of osteoarthritis (OA) as a collaboration between the American College of Rheumatology (ACR) and...
OBJECTIVE
To develop an evidence-based guideline for the comprehensive management of osteoarthritis (OA) as a collaboration between the American College of Rheumatology (ACR) and the Arthritis Foundation, updating the 2012 ACR recommendations for the management of hand, hip, and knee OA.
METHODS
We identified clinically relevant population, intervention, comparator, outcomes questions and critical outcomes in OA. A Literature Review Team performed a systematic literature review to summarize evidence supporting the benefits and harms of available educational, behavioral, psychosocial, physical, mind-body, and pharmacologic therapies for OA. Grading of Recommendations Assessment, Development and Evaluation methodology was used to rate the quality of the evidence. A Voting Panel, including rheumatologists, an internist, physical and occupational therapists, and patients, achieved consensus on the recommendations.
RESULTS
Based on the available evidence, either strong or conditional recommendations were made for or against the approaches evaluated. Strong recommendations were made for exercise, weight loss in patients with knee and/or hip OA who are overweight or obese, self-efficacy and self-management programs, tai chi, cane use, hand orthoses for first carpometacarpal (CMC) joint OA, tibiofemoral bracing for tibiofemoral knee OA, topical nonsteroidal antiinflammatory drugs (NSAIDs) for knee OA, oral NSAIDs, and intraarticular glucocorticoid injections for knee OA. Conditional recommendations were made for balance exercises, yoga, cognitive behavioral therapy, kinesiotaping for first CMC OA, orthoses for hand joints other than the first CMC joint, patellofemoral bracing for patellofemoral knee OA, acupuncture, thermal modalities, radiofrequency ablation for knee OA, topical NSAIDs, intraarticular steroid injections and chondroitin sulfate for hand OA, topical capsaicin for knee OA, acetaminophen, duloxetine, and tramadol.
CONCLUSION
This guideline provides direction for clinicians and patients making treatment decisions for the management of OA. Clinicians and patients should engage in shared decision-making that accounts for patients' values, preferences, and comorbidities. These recommendations should not be used to limit or deny access to therapies.
Topics: Hand Joints; Humans; Osteoarthritis; Osteoarthritis, Hip; Osteoarthritis, Knee
PubMed: 31908163
DOI: 10.1002/art.41142 -
International Journal of Molecular... Mar 2020Osteoarthritis (OA) is the most common joint disease that causes pain and disability in the adult population. OA is primarily caused by trauma induced by an external... (Review)
Review
Osteoarthritis (OA) is the most common joint disease that causes pain and disability in the adult population. OA is primarily caused by trauma induced by an external force or by age-related cartilage damage. Chondrocyte hypertrophy or chondrocyte senescence is thought to play a role in the initiation and progression of OA. Although chondrocyte hypertrophy and cell death are both crucial steps during the natural process of endochondral bone formation, the abnormal activation of these two processes after injury or during aging seems to accelerate the progression of OA. However, the exact mechanisms of OA progression and these two processes remain poorly understood. Chondrocyte senescence and hypertrophy during OA share various markers and processes. In this study, we reviewed the changes that occur during chondrocyte hypertrophy or senescence in OA and the attempts that were made to regulate them. Regulation of hypertrophic or senescent chondrocytes might be a potential therapeutic target to slow down or stop OA progression; thus, a better understanding of the processes is required for management.
Topics: Animals; Biomarkers; Cartilage, Articular; Cell Differentiation; Cell Proliferation; Cellular Senescence; Chondrocytes; Chondrogenesis; Disease Progression; Disease Susceptibility; Gene Expression Regulation; Humans; Hypertrophy; Osteoarthritis; Osteogenesis; Signal Transduction
PubMed: 32235300
DOI: 10.3390/ijms21072358