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1.
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.
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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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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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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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Use of Vitamin D Supplements in Osteoarthritis: An Observational Study in a Tertiary Health Care Facility.
Thomas, JE, Bhat, AK, Rao, M, Guddattu, V, Sekhar M, S
Journal of the American College of Nutrition. 2019;(3):227-234
Abstract
OBJECTIVE The purpose of the study was to assess impact of vitamin D supplements on the disease progression and overall health of osteoarthritis (OA) patients. METHODOLOGY A cohort study was carried out for 8 months (August 2017-March 2018) in the Orthopedics Department of Kasturba Hospital, Manipal, India, a tertiary care hospital. One hundred and forty-two patients who were diagnosed with OA (grades 1-3) with low serum 25(OH)D levels (severely deficient, deficient, or insufficient) were selected for the study. These patients were categorized into two cohorts: a control cohort (CC) and a study cohort (SC). CC members were patients (n = 71) who had not received vitamin D supplements, and SC members were patients (n = 71) who had received vitamin D supplements. Severity grading of OA, pain score, and health assessment were performed using the Kellgren-Laurence grading score, visual analogue scale (VAS), and WOMAC, respectively, at baseline and after 3 months of follow-up. RESULTS Subjects in the both CC and SC reported no statistically significant difference (similar in both group) in severity grade (p = 0.303), pain score (p = 0.099), parathyroid hormone (PTH) (p = 0.083), and health status (p = 0.76) at baseline. After 3 months of follow-up (post vitamin D supplementation), OA patients have shown statistically significant difference in severity grades, serum 25(OH)D status, PTH level (p < 0.001), and overall health status (p = 0.001) in the SC with respect to baseline. Likewise, percentage distribution of positive changes was significantly higher in severity grade, pain score, serum 25(OH)D level, overall health status (p < 0.001), and PTH (p = 0.040) of SC as compared to CC at follow-up. CONCLUSION Vitamin D supplements have significantly improved serum 25(OH)D levels, PTH, severity grade, and pain score of OA patients. Most importantly, vitamin D supplements have shown improvement in the overall health of OA patients, emphasizing the place of vitamin D supplements in the management of OA. Clinical Trial Registry-India (CTRI) registration no: CTRI/2017/12/011031.
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Rosa canina - Rose hip pharmacological ingredients and molecular mechanics counteracting osteoarthritis - A systematic review.
Gruenwald, J, Uebelhack, R, Moré, MI
Phytomedicine : international journal of phytotherapy and phytopharmacology. 2019;:152958
Abstract
BACKGROUND The successful use of rose hip for the treatment of osteoarthritis is well documented. Several randomized placebo controlled double-blind studies, as mono or combination therapy, have demonstrated treatment efficacy as well as excellent tolerability. PURPOSE This review focuses on the molecular mechanism underlying the clinical effects of rose hip in osteoarthritis (OA). METHODS The database Medline was screened - using the search term "Rosa canina" or "rose hip" - for publications on pharmacological or mechanistic studies with relevance to OA; in addition for findings on pharmacologically active constituents as well as clinical studies. The screening results were complemented by following-up on cited literature. RESULTS In particular, 24 pharmacological studies on Rosa canina or preparations thereof were considered relevant. Potent antioxidant radical scavenging effects are well documented for numerous rose hip constituents besides Vitamin C. Furthermore, anti-inflammatory activities include the reduction of pro-inflammatory cytokines and chemokines, reduction of NF-kB signaling, inhibition of pro-inflammatory enzymes, including COX1/2, 5-LOX and iNOS, reduction of C-reactive protein levels, reduction of chemotaxis and chemoluminescence of PMNs, and an inhibition of pro-inflammatory metalloproteases. CONCLUSION The antioxidant and anti-inflammatory effects of Rosa canina match its clinical action - especially considering new findings on the pharmacological disease pattern of OA. The entirety of several compounds including phenolics, terpenoids, galactolipids, carotenoids, fruit acids and fatty oils can be considered responsible for the observed pharmacological and clinical effects. Further research is needed to eludicate how and in which manner single rose hip compounds interact with their molecular pharmacological targets.