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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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2.
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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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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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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Curcumagalactomannoside/Glucosamine Combination Improved Joint Health Among Osteoarthritic Subjects as Compared to Chondroitin Sulfate/Glucosamine: Double-Blinded, Randomized Controlled Study.
Khanna, A, Das, SS, Smina, TP, Thomas, JV, Kunnumakkara, AB, Maliakel, B, Krishnakumar, IM, Mohanan, R
Journal of alternative and complementary medicine (New York, N.Y.). 2020;(10):945-955
Abstract
Objective: A combination of curcumagalactomannosides (CGM) (400 mg) with glucosamine hydrochloride (GLN) (500 mg) was evaluated against a standard dietary supplement combination chondroitin sulfate (CHN) (415 mg)/GLN (500 mg) for their effectiveness in alleviating the pain and symptoms among osteoarthritic subjects. Design: Randomized, double-blinded and active-controlled study. Settings/Location: The study was conducted in a hospital-based research center in Vadodara, Gujarat, India. Subjects: Eighty subjects (38 males and 42 females), with confirmed osteoarthritis (OA) (Class I-III), were randomized into two parallel groups designated as Group I (CGM-GLN) and Group II (CHN-GLN). Interventions: All the study subjects were supplemented with their corresponding intervention capsules (ether CGM along with GLN or CHN along with GLN), as a single oral dose twice a day, once in the morning 10-15 min before breakfast and again in the evening before dinner, for 84 days. Outcome measures: A validated treadmill uphill walking protocol was used for the study, and the efficiency of supplementation was evaluated using visual analogue scale (VAS) score, Karnofsky Performance Scale (KPS) score, and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaire at the baseline, 28th, and 84th day following the treatment. Mechanism of action of CGM-GLN combination was analyzed by measuring the levels of serum inflammatory markers interleukin 1 beta (IL-1β), interleukin 6 (IL-6), and soluble vascular cell adhesion molecule-1 (sVCAM) at the baseline and 84th day. Results: CGM-GLN was found to offer significant beneficial effects to pain, stiffness, and physical function of OA subjects compared with CHN-GLN, which was evident from the improvement in walking performance, VAS score, KPS score, and WOMAC score. The efficiency of CGM-GLN was almost double compared with the CHN-GLN by the end of the study (84th day). A significant reduction of inflammatory serum marker levels was observed among CGM-GLN subjects compared with CHN-GLN subjects. Compared with the baseline, CGM-GLN produced 54.52%, 59.08%, and 22.03% reduction in IL-1β, IL-6, and sVCAM levels, respectively. Whereas CHN-GLN group of subjects expressed only 23.17%, 21.38%, and 6.82% reduction in IL-1β, IL-6, and sVCAM levels, respectively. Conclusions: In conclusion, the present study demonstrated the potential benefits of CGM-GLN supplements in alleviating the symptoms and function of OA subjects compared with the standard CHN-GLN treatment. The augmented efficacy of CGM-GLN combination could be attributed to the enhanced anti-inflammatory effect of CGM.
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Polygenic risk scores indicates genetic overlap between peripheral pain syndromes and chronic postsurgical pain.
van Reij, RRI, Voncken, JW, Joosten, EAJ, van den Hoogen, NJ
Neurogenetics. 2020;(3):205-215
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Abstract
Chronic postsurgical pain (CPSP) is a debilitating chronic pain condition that has a substantial effect on quality of life. CPSP shows considerable clinical overlap with different chronic peripheral pain syndromes, suggesting a shared aetiology. This study aims to assess the genetic overlap between different chronic pain syndromes and CPSP, providing relevant biological context for potential chronic pain markers of CPSP. To analyse the genetic overlap between CPSP and chronic peripheral pain syndromes, recent GWAS studies were combined for polygenic risk scores (PRS) analysis, using a cohort of CPSP patients as starting point. Biological contextualisation of genetic marker, overlap between CPSP and chronic pain syndromes, was assessed through Gene Ontology (GO), using Pathway Scoring Algorithm (PASCAL) and REVIGO. PRS analyses suggest a significant genetic overlap between CPSP and 3 chronic pain disorders: chronic widespread pain (CWP, p value threshold = 0.003, R2 0.06, p = 0.003), rheumatoid arthritis (RA, p value threshold = 0.0177, R2 = 0.04, p = 0.017) and possibly sciatica (p value threshold = 0.00025, R2 = 0.03, p = 0.045). Whereas no significant genetic overlap was found with cluster headache and migraine, the outcome for osteoarthritis (OA) was inconsistent between the cohorts. This is likely related to cohort composition, as repeated random reallocation of patients' nullified CPSP/OA outcome variation between the discovery and replication cohorts. GO analyses suggested an aetiological involvement of genetic markers that control neurological signalling (specifically sodium channels) and inflammatory response. The current study reaffirms the impact of sample size, cohort composition and open data accessibility on the unbiased identification of genetic overlap across disorders. In conclusion, this study is the first to report genetic overlap between regulatory processes implicated in CPSP and chronic peripheral pain syndromes. Interaction between neurological signalling and inflammatory response may explain the genetic overlap between CPSP, CWP and RA. Enhanced understanding of mechanisms underlying chronification of pain will aid the development of new therapeutic strategies for CPSP with sodium channel biochemistry as a potential candidate.
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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.
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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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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.