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1.
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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2.
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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Efficacy of a Combination of Conservative Therapies vs an Education Comparator on Clinical Outcomes in Thumb Base Osteoarthritis: A Randomized Clinical Trial.
Deveza, LA, Robbins, SR, Duong, V, Bennell, KL, Vicenzino, B, Hodges, PW, Wajon, A, Jongs, R, Riordan, EA, Fu, K, et al
JAMA internal medicine. 2021;(4):429-438
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Abstract
IMPORTANCE A combination of conservative treatments is commonly used in clinical practice for thumb base osteoarthritis despite limited evidence for this approach. OBJECTIVE To determine the efficacy of a 6-week combination of conservative treatments compared with an education comparator. DESIGN, SETTING, AND PARTICIPANTS Randomized, parallel trial with 1:1 allocation ratio among people aged 40 years and older with symptomatic and radiographic thumb base osteoarthritis in a community setting in Australia. INTERVENTIONS The intervention group (n = 102) received education on self-management and ergonomic principles, a base-of-thumb splint, hand exercises, and diclofenac sodium, 1%, gel. The comparator group (n = 102) received education on self-management and ergonomic principles alone. Intervention use was at participants' discretion from 6 to 12 weeks. MAIN OUTCOMES AND MEASURES Hand function (Functional Index for Hand Osteoarthritis; 0-30) and pain (visual analog scale; 0-100 mm) were measured at week 6 (primary time point) and week 12. An α of .027 was used at week 6 to account for co-primary outcomes. RESULTS Of the 204 participants randomized, 195 (96%) and 194 (95%) completed follow-ups at 6 and 12 weeks, respectively; the mean (SD) age of the population was 65.6 (8.1) years, and 155 (76.0%) were female. At week 6, hand function improved significantly more in the intervention group than the comparator (between-group difference, -1.7 units; 97.3% CI, -2.9 to -0.5; P = .002). This trend was sustained at 12 weeks (-2.4 units; 95% CI, -3.5 to -1.3; P < .001). Pain scores improved similarly at week 6 (between-group difference, -4.2 mm; 97.3% CI, -11.3 to 3.0; P = .19). At week 12, pain reduction was significantly greater in the intervention group (-8.6 mm; 95% CI, -15.2 to -2.0; P = .01). There were 34 nonserious adverse events, all in the intervention group-mostly skin reactions and exercise-related pain exacerbations. CONCLUSIONS AND RELEVANCE In this randomized clinical trial of people with thumb base osteoarthritis, combined treatments provided small to medium and potentially clinically beneficial effects on hand function but not pain. TRIAL REGISTRATION Australian New Zealand Clinical Trials Registry Identifier: ACTRN12616000353493.
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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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Bioinformatics analysis of differentially expressed genes in subchondral bone in early experimental osteoarthritis using microarray data.
Wang, Z, Ji, Y, Bao, HW
Journal of orthopaedic surgery and research. 2020;(1):310
Abstract
BACKGROUND Osteoarthritis (OA) is the most common arthritic disease in humans, affecting the majority of individuals over 65 years of age. The aim of this study is to identify the gene expression profile specific to subchondral bone in OA by comparing the different expression profiles in experimental and sham-operation groups. METHODS Gene expression profile GSE30322 was downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were obtained by limma package. And Database for Annotation, Visualization and Integrated Discovery (DAVID) databases were further used to identify the potential gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Furthermore, a protein-protein interaction (PPI) network was constructed and significant modules were extracted. RESULTS Totally, 588 DEGs were identified including 199 upregulated DEGs and 389 downregulated DEGs screened in OA and sham-operation. GO showed that DEGs were significantly enhanced for ribosomal subunit export from nucleus and molting cycle. KEGG pathway analysis revealed that target genes were enriched in thiamine metabolism. CONCLUSION These key candidate DEGs that affect the progression of OA, and these genes might serve as potential therapeutic targets for OA.
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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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Foot structure and lower limb function in individuals with midfoot osteoarthritis: a systematic review.
Lithgow, MJ, Munteanu, SE, Buldt, AK, Arnold, JB, Kelly, LA, Menz, HB
Osteoarthritis and cartilage. 2020;(12):1514-1524
Abstract
OBJECTIVE To determine how foot structure and lower limb function differ between individuals with and without midfoot osteoarthritis (OA). DESIGN Electronic databases were searched from inception until May 2020. To be eligible, studies needed to (1) include participants with radiographically confirmed midfoot OA, with or without midfoot symptoms, (2) include a control group of participants without radiographic midfoot OA or without midfoot symptoms, and (3) report outcomes of foot structure, alignment, range of motion or any measures of lower limb function during walking. Screening and data extraction were performed by two independent assessors, with disagreements resolved by a third independent assessor. The methodological quality of included studies was assessed using the National Institutes of Health Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. RESULTS A total of 1,550 records were screened by title and abstract and 11 met the inclusion criteria. Quantitative synthesis indicated that individuals who had midfoot OA had a more pronated foot posture, greater first ray mobility, less range of motion in the subtalar joint and first metatarsophalangeal joints, longer central metatarsals and increased peak plantar pressures, pressure time integrals and contact times in the heel and midfoot during walking. Meta-analysis could not be performed as the data were not sufficiently homogenous. CONCLUSIONS There are several differences in foot structure and lower limb function between individuals with and without midfoot OA. Future research with more consistent case definitions and detailed biomechanical models would further our understanding of potential mechanisms underlying the development of midfoot OA.
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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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Effect of Two Meal Replacement strategies on Cardiovascular Risk Parameters in Advanced Age Patients with Obesity and Osteoarthritis.
López-Gómez, JJ, Izaola-Jauregui, O, Primo-Martín, D, Torres-Torres, B, Gómez-Hoyos, E, Ortolá-Buigues, A, Martín-Ferrero, MA, De Luis-Román, DA
Nutrients. 2020;(4)
Abstract
BACKGROUND AND AIMS Meal replacement diets consist of replacing one or more meals with an artificial nutritional supplement. The objective of this study was to compare the effect of one against two meal replacement strategies on body composition and cardiovascular risk parameters in patients with obesity. METHODS A randomized clinical trial was designed with a modified hypocaloric diet with an artificial nutritional preparation replacing one or two meals for three months in patients with obesity and osteoarthritis pending orthopedic surgery. An anthropometric evaluation and a measurement of the body composition were done with bioelectrical impedance measurement at the beginning and at three months. RESULTS A total of 112 patients were recruited. Fifty-two patients (46.4%) were randomized to one replacement and 60 patients (53.6%) to two meal replacements. Eighty-one patients (72.3%) were women, and the average age was 61 (11.03) years. The percentage of weight loss at three months was 8.27 (4.79)% (one meal replacement: 7.98 (5.97)%; two meal replacements: 8.50 (3.48)%; p = 0.56). A decrease in fat mass measured by the fat mass index (FMI) was detected (one meal replacement: -2.15 (1.45) kg/m2 vs. two meal replacements: -2.78 (2.55) kg/m2; p > 0.05), and a relative increase in fat-free mass was observed (one meal replacement: +3.57 (4.61)% vs. two meal replacements: +2.14 (4.45)%; p > 0.05). A decrease in HOMA-IR, systolic blood pressure (SBP), and total cholesterol was observed in both groups without differences between them. CONCLUSIONS The substitution strategies of one or two meal replacements were effective in weight loss and fat mass decrease without differences between the two groups. An improvement in lipid parameters, glycemic control, and systolic blood pressure was observed without differences between strategies.
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Efficacy and safety of a supplement combination for hand osteoarthritis pain: protocol for an internet-based randomised placebo-controlled trial (The RADIANT study).
Liu, X, Robbins, S, Eyles, J, Fedorova, T, Virk, S, Deveza, LA, McLachlan, A, Hunter, D
BMJ open. 2020;(2):e035672
Abstract
INTRODUCTION Hand osteoarthritis (HOA) is a highly prevalent disabling joint disease. The current management regimens are limited. Potentially as a consequence, many people turn to complementary and alternative medicines for symptomatic relief. A combination of two or more supplements is common in clinical practice; however, evidence for the efficacy of this approach is lacking. The aim of this study is to investigate the efficacy of a supplement combination for treating symptomatic HOA in comparison to placebo. METHODS AND ANALYSIS The RADIANT study is an internet-based, parallel, superiority, double-blind, placebo-controlled, randomised, two-arm clinical trial. A participatory design is used to facilitate the study procedures. One hundred and six participants aged over 40 years with painful HOA and structural change on X-ray (Kellgren and Lawrence grade (KLG) ≥2) will be recruited from the community and randomly allocated to receive either a supplement combination composed of: (1) combined supplement containing Boswellia serrata extract, pine bark extract and methylsulfonylmethane and (2) curcumin or placebo for 12 weeks. The primary outcome will be 12-week change in hand pain on a visual analogue scale (VAS). Main secondary outcomes include adverse events, change in hand function, patient global assessment of disease activity and quality of life. A range of additional measures will be recorded, and an individual patient placebo response will be performed. The primary analysis will be conducted using an intention-to-treat approach. Adverse events will be monitored weekly throughout the study. ETHICS AND DISSEMINATION This protocol has been approved by the University of Sydney Human Research Ethics Committee (HREC No. 2018/766). Dissemination will occur through conferences, social media, scientific publications and PhD thesis. TRIAL REGISTRATION NUMBER Australian New Zealand Clinical Trials Registry (ACTRN12619000835145); Pre-results.