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1.
Epidemiology of osteoarthritis.
Allen, KD, Thoma, LM, Golightly, YM
Osteoarthritis and cartilage. 2022;(2):184-195
Abstract
OBJECTIVE To summarize the current state of the evidence regarding osteoarthritis (OA) prevalence, incidence and risk factors at the person-level and joint-level. DESIGN This was a narrative review that took a comprehensive approach regarding inclusion of potential risk factors. The review complements prior reviews of OA epidemiology, with a focus on new research and emerging topics since 2017, as well as seminal studies. RESULTS Studies continue to illustrate the high prevalence of OA worldwide, with a greater burden among older individuals, women, some racial and ethnic groups, and individuals with lower socioeconomic status. Modifiable risk factors for OA with the strongest evidence are obesity and joint injury. Topics of high interest or emerging evidence for a potential association with OA risk or progression include specific vitamins and diets, high blood pressure, genetic factors, metformin use, bone mineral density, abnormal joint shape and malalignment, and lower muscle strength/quality. Studies also continue to highlight the heterogenous nature of OA, with strong interest in understanding and defining OA phenotypes. CONCLUSIONS OA is an increasingly prevalent condition with worldwide impacts on many health outcomes. The strong evidence for obesity and joint injury as OA risk factors calls for heightened efforts to mitigate these risks at clinical and public health levels. There is also a need for continued research regarding how potential person- and joint-level risk factors may interact to influence the development and progression of OA.
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An Evidence-based Review of Medicinal Plants used in Traditional Persian Medicine for Treatment of Osteoarthritis.
Karami, S, Shamshiri, S, Abdollahi, M, Rahimi, R
Current drug discovery technologies. 2021;(2):244-271
Abstract
Osteoarthritis (OA) is known to be the leading cause of pain and disability in the elderly. The prevalence of this disease in adults over 60 years was 9.6% in men and 18% in women. The therapeutic goals of this disease generally include pain relief with the least side effects, improvement of articular function and improvement of life, in which pharmacological and nonpharmacological treatments are performed in different protocols. Due to the common side effects of pain relievers and complaints after invasive joint surgeries, there is a growing interest in the use of Traditional and Complementary protocols in OA treatment. In this paper, different sources of Traditional Persian Medicine (TPM) were searched to obtain any evidence evaluating any medicinal plants in the management of OA. Over 250 effective medicinal plants for the treatment of OA have been introduced in these sources, and by searching electronic databases including PubMed and Scopus, we have found that of these plants, 39 have direct or indirect evidence in the treatment of this complication by different mechanism of actions such as effect on Body mass index (BMI), obesity and dyslipidemia, anti-inflammatory, anti-nociceptive and antioxidant activity. The most important medicinal plants with direct evidence in the management of OA are Allium sativum, Commiphora mukul, Linum usitatissimum, Matricaria chamomilla, Nigella sativa, Zingiber officinale, and Piper nigrum. Medicinal plants seem to be a valuable source for discovering and identifying new drugs for treatment of OA; however, since most of the studies are preclinical, further clinical trials are required to achieve more conclusive results.
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Cardiovascular Drugs and Osteoarthritis: Effects of Targeting Ion Channels.
Vaiciuleviciute, R, Bironaite, D, Uzieliene, I, Mobasheri, A, Bernotiene, E
Cells. 2021;(10)
Abstract
Osteoarthritis (OA) and cardiovascular diseases (CVD) share many similar features, including similar risk factors and molecular mechanisms. A great number of cardiovascular drugs act via different ion channels and change ion balance, thus modulating cell metabolism, osmotic responses, turnover of cartilage extracellular matrix and inflammation. These drugs are consumed by patients with CVD for many years; however, information about their effects on the joint tissues has not been fully clarified. Nevertheless, it is becoming increasingly likely that different cardiovascular drugs may have an impact on articular tissues in OA. Here, we discuss the potential effects of direct and indirect ion channel modulating drugs, including inhibitors of voltage gated calcium and sodium channels, hyperpolarization-activated cyclic nucleotide-gated channels, β-adrenoreceptor inhibitors and angiotensin-aldosterone system affecting drugs. The aim of this review was to summarize the information about activities of cardiovascular drugs on cartilage and subchondral bone and to discuss their possible consequences on the progression of OA, focusing on the modulation of ion channels in chondrocytes and other joint cells, pain control and regulation of inflammation. The implication of cardiovascular drug consumption in aetiopathogenesis of OA should be considered when prescribing ion channel modulators, particularly in long-term therapy protocols.
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Relationship between the Gut Microbiome and Osteoarthritis Pain: Review of the Literature.
Sánchez Romero, EA, Meléndez Oliva, E, Alonso Pérez, JL, Martín Pérez, S, Turroni, S, Marchese, L, Villafañe, JH
Nutrients. 2021;(3)
Abstract
BACKGROUND Osteoarthritis (OA) is the most common form of chronic pain in Europe (34%), representing a great economic and social cost to society. There are studies that suggest an intestine-brain-articulation axis and hint at the existence of low-grade intestinal inflammation in OA, which would be related to an alteration of the microbiota and to the impairment of the epithelial barrier, with leakage of the microbial components. PURPOSE The purpose of this study was to review the association between gut microbiome and pain in the OA population through a review of the literature. METHODS A literature search was conducted to identify all available studies on the association between the gut microbiome and pain in the OA population, with no publication date limit until September 2020 and no language limit, in the MEDLINE, CINAHL, Web of Science and Cochrane Central Register of Controlled Trials databases. RESULTS Only three of 2084 studies detected and analyzed by performing the proposed searches in the detailed databases, were finally selected for this review, of which one was with and two were without intervention. These studies only weakly support a relationship between the gut microbiome and OA, specifically a correlation between certain taxa or microbial products and the inflammatory landscape and severity of OA symptoms, including knee pain. Conclusions: Despite encouraging results, this review highlights the paucity of high-quality studies addressing the potential role of the gut microbiome in OA-related pain, along with the disparity of the techniques used so far, making it impossible to draw firm conclusions on the topic.
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Current status of functional MRI of osteoarthritis for diagnosis and prognosis.
Juras, V, Chang, G, Regatte, RR
Current opinion in rheumatology. 2020;(1):102-109
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Abstract
PURPOSE OF REVIEW Osteoarthritis is a major source of disability, pain and socioeconomic cost worldwide. The epidemiology of the disorder is multifactorial including genetic, biological and biomechanical components, some of them detectable by MRI. This review provides the most recent update on MRI biomarkers which can provide functional information of the joint structures for diagnosis, prognosis and treatment response monitoring in osteoarthritis trials. RECENT FINDINGS Compositional or functional MRI can provide clinicians with valuable information on glycosaminoglycan content (chemical exchange saturation transfer, sodium MRI, T1ρ) and collagen organization (T2, T2, apparent diffusion coefficient, magnetization transfer) in joint structures. Other parameters may also provide useful information, such as volumetric measurements of joint structures or advanced image data postprocessing and analysis. Automated tools seem to have a great potential to be included in these efforts providing standardization and acceleration of the image data analysis process. SUMMARY Functional or compositional MRI has great potential to provide noninvasive imaging biomarkers for osteoarthritis. Osteoarthritis as a whole joint condition needs to be diagnosed in early stages to facilitate selection of patients into clinical trials and/or to measure treatment effectiveness. Advanced evaluation including machine learning, neural networks and multidimensional data analysis allow for wall-to-wall understanding of parameter interactions and their role in clinical evaluation of osteoarthritis.
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Mangiferin: Possible uses in the prevention and treatment of mixed osteoarthritic pain.
Garrido-Suárez, BB, Garrido, G, Piñeros, O, Delgado-Hernández, R
Phytotherapy research : PTR. 2020;(3):505-525
Abstract
Osteoarthritis (OA) pain has been proposed to be a mixed pain state, because in some patients, central nervous system factors are superimposed upon the more traditional peripheral factors. In addition, a considerable amount of preclinical and clinical evidence has shown that, accompanying the central neuroplasticity changes and partially driven by a peripheral nociceptive input, a real neuropathic component occurs that are particularly linked to disease severity and progression. Hence, innovative strategies targeting neuroprotection and particularly neuroinflammation to prevent and treat OA pain could be introduced. Mangiferin (MG) is a glucosylxanthone that is broadly distributed in higher plants, such as Mangifera indica L. Previous studies have documented its analgesic, anti-inflammatory, antioxidant, neuroprotective, and immunomodulatory properties. In this paper, we propose its potential utility as a multitargeted compound for mixed OA pain, even in the context of multimodal pharmacotherapy. This hypothesis is supported by three main aspects: the cumulus of preclinical evidence around this xanthone, some preliminary clinical results using formulations containing MG in clinical musculoskeletal or neuropathic pain, and by speculations regarding its possible mechanism of action according to recent advances in OA pain knowledge.
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Applications of Photobiomodulation Therapy to Musculoskeletal Disorders and Osteoarthritis with Particular Relevance to Canada.
Gendron, DJ, Hamblin, MR
Photobiomodulation, photomedicine, and laser surgery. 2019;(7):408-420
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Abstract
Background: Musculoskeletal disorders caused by osteoarthritis (MSDs/OA) are a growing problem in the modern industrialized society in Canada. Overall aging of the general population and a progressive lack of exercise contribute to this alarming increase. Moreover, a range of chronic conditions including cardiovascular and mental diseases show significantly higher comorbidity with MSDs/OA. Conventional medical treatment for MSDs/OA includes nonsteroidal anti-inflammatory drugs and opiate pain killers. These drugs have major drawbacks such as a relative lack of efficacy, potential for addiction, and even death (Vioxx scandal). Photobiomodulation (PBM) was discovered over 50 years ago but has still not attained widespread acceptance by the medical community. This is partly due to uncertainty about the precise molecular mechanisms of action and a bewildering array of different wavelengths and dosimetric parameters employed in reported studies. Objective: The goal of this review was to survey literature reports of PBM, also known as low-level laser therapy used for treatment of MSDs/OA, concentrating on the growth over time, different wavelengths employed, and application to different joints. Methods: We searched the PubMed database for publication of study on PBM to treat the most common joints. Results: We show that the field of PBM to treat MSDs/OA is expanding exponentially over the past 20 years. A trend has emerged over time for more power to achieve better effective treatments, and the understanding of the physiological effect of safe parameters has improved. There is, however, no consensus on the best set of parameters to treat a specific patient indication. Conclusions: Finally, we highlight gaps in our knowledge and the barriers to further clinical trials. We suggest that the growing body of evidence indicating efficacy, and the almost total lack of side effects, should encourage continued clinical research to support clinical applications where better rehabilitation treatments are much needed.
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The Role of Autophagy in Chondrocyte Metabolism and Osteoarthritis: A Comprehensive Research Review.
Luo, P, Gao, F, Niu, D, Sun, X, Song, Q, Guo, C, Liang, Y, Sun, W
BioMed research international. 2019;:5171602
Abstract
Chondrocytes are the sole cellular constituents of normal cartilage. The degeneration and apoptosis of these cells are considered the main cause of osteoarthritis (OA). Previous studies have suggested that the enhancement of autophagy in chondrocytes can delay the progression of osteoarthritis by affecting intracellular metabolic activity, i.e., by regulating the metabolism of nutrients, which can delay cell aging and death. In this review, we explored the relationship between autophagy and chondrocyte metabolism and provided new ideas for the prevention and treatment of OA.
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The burden of metabolic syndrome on osteoarthritic joints.
Dickson, BM, Roelofs, AJ, Rochford, JJ, Wilson, HM, De Bari, C
Arthritis research & therapy. 2019;(1):289
Abstract
BACKGROUND The prevalence of osteoarthritis (OA) increases with obesity, with up to two thirds of the elderly obese population affected by OA of the knee. The metabolic syndrome (MetS), frequently associated with central obesity and characterised by elevated waist circumference, raised fasting plasma glucose concentration, raised triglycerides, reduced high-density lipoproteins, and/or hypertension, is implicated in the pathogenesis of OA. This narrative review discusses the mechanisms involved in the influence of MetS on OA, with a focus on the effects on macrophages and chondrocytes. MAIN TEXT A skewing of macrophages towards a pro-inflammatory M1 phenotype within synovial and adipose tissues is thought to play a role in OA pathogenesis. The metabolic perturbations typical of MetS are important drivers of pro-inflammatory macrophage polarisation and activity. This is mediated via alterations in the levels and activities of the cellular nutrient sensors 5' adenosine monophosphate-activated protein kinase (AMPK) and mammalian target of rapamycin complex 1 (mTORC1), intracellular accumulation of metabolic intermediates such as succinate and citrate, and increases in free fatty acids (FFAs) and hyperglycaemia-induced advanced glycation end-products (AGEs) that bind to receptors on the macrophage surface. Altered levels of adipokines, including leptin and adiponectin, further influence macrophage polarisation. The metabolic alterations in MetS also affect the cartilage through direct effects on chondrocytes by stimulating the production of pro-inflammatory and catabolic factors and possibly by suppressing autophagy and promoting cellular senescence. CONCLUSIONS The influence of MetS on OA pathogenesis involves a wide range of metabolic alterations that directly affect macrophages and chondrocytes. The relative burden of intra-articular versus systemic adipose tissue in the MetS-associated OA remains to be clarified. Understanding how altered metabolism interacts with joints affected by OA is crucial for the development of further strategies for treating this debilitating condition, such as supplementing existing therapies with metformin and utilising ω-3 fatty acid derivatives to restore imbalances in ω-3 and ω-6 fatty acids.
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Dietary supplements for treating osteoarthritis: a systematic review and meta-analysis.
Liu, X, Machado, GC, Eyles, JP, Ravi, V, Hunter, DJ
British journal of sports medicine. 2018;(3):167-175
Abstract
OBJECTIVE To investigate the efficacy and safety of dietary supplements for patients with osteoarthritis. DESIGN An intervention systematic review with random effects meta-analysis and meta-regression. DATA SOURCES MEDLINE, EMBASE, Cochrane Register of Controlled Trials, Allied and Complementary Medicine and Cumulative Index to Nursing and Allied Health Literature were searched from inception to April 2017. STUDY ELIGIBILITY CRITERIA Randomised controlled trials comparing oral supplements with placebo for hand, hip or knee osteoarthritis. RESULTS Of 20 supplements investigated in 69 eligible studies, 7 (collagen hydrolysate, passion fruit peel extract, Curcuma longa extract, Boswellia serrata extract, curcumin, pycnogenol and L-carnitine) demonstrated large (effect size >0.80) and clinically important effects for pain reduction at short term. Another six (undenatured type II collagen, avocado soybean unsaponifiables, methylsulfonylmethane, diacerein, glucosamine and chondroitin) revealed statistically significant improvements on pain, but were of unclear clinical importance. Only green-lipped mussel extract and undenatured type II collagen had clinically important effects on pain at medium term. No supplements were identified with clinically important effects on pain reduction at long term. Similar results were found for physical function. Chondroitin demonstrated statistically significant, but not clinically important structural improvement (effect size -0.30, -0.42 to -0.17). There were no differences between supplements and placebo for safety outcomes, except for diacerein. The Grading of Recommendations Assessment, Development and Evaluation suggested a wide range of quality evidence from very low to high. CONCLUSIONS The overall analysis including all trials showed that supplements provided moderate and clinically meaningful treatment effects on pain and function in patients with hand, hip or knee osteoarthritis at short term, although the quality of evidence was very low. Some supplements with a limited number of studies and participants suggested large treatment effects, while widely used supplements such as glucosamine and chondroitin were either ineffective or showed small and arguably clinically unimportant treatment effects. Supplements had no clinically important effects on pain and function at medium-term and long-term follow-ups.