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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.
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Measurement of synovial tissue volume in knee osteoarthritis using a semiautomated MRI-based quantitative approach.
Perry, TA, Gait, A, O'Neill, TW, Parkes, MJ, Hodgson, R, Callaghan, MJ, Arden, NK, Felson, DT, Cootes, TF
Magnetic resonance in medicine. 2019;(5):3056-3064
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PURPOSE Synovitis is common in knee osteoarthritis and is associated with both knee pain and progression of disease. Semiautomated methods have been developed for quantitative assessment of structure in knee osteoarthritis. Our aims were to apply a novel semiautomated assessment method using 3D active appearance modeling for the quantification of synovial tissue volume (STV) and to compare its performance with conventional manual segmentation. METHODS Thirty-two sagittal T1 -weighted fat-suppressed contrast-enhanced MRIs were assessed for STV by a single observer using 1) manual segmentation and 2) a semiautomated approach. We compared the STV analysis using the semiautomated and manual segmentation methods, including the time taken to complete the assessments. We also examined the reliability of STV assessment using the semiautomated method in a subset of 12 patients who had participated in a clinical trial of vitamin D therapy in knee osteoarthritis. RESULTS There was no significant difference in STV using the semiautomated quantitative method compared to manual segmentation, mean difference = 207.2 mm3 (95% confidence interval -895.2 to 1309.7). The semiautomated method was significantly quicker than manual segmentation (18 vs. 71 min). For the semiautomated method, intraobserver agreement was excellent (intraclass correlation coefficient (3,1) = 0.99) and interobserver agreement was very good (intraclass correlation coefficient (3,1) = 0.83). CONCLUSION We describe the application of a semiautomated method that is accurate, reliable, and quicker than manual segmentation for assessment of STV. The method may help increase efficiency of image assessment in large imaging studies and may also assist investigation of treatment efficacy in knee osteoarthritis.
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Sulphurous mud-bath therapy for treatment of chronic low back pain caused by lumbar spine osteoarthritis.
Costantino, M, Conti, V, Corbi, G, Marongiu, F, Marongiu, MB, Filippelli, A
Internal and emergency medicine. 2019;(1):187-190
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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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Comparative Analyses of Pharmaceuticals or Food Supplements Containing Chondroitin Sulfate: Are Their Bioactivities Equivalent?
Stellavato, A, Restaino, OF, Vassallo, V, Finamore, R, Ruosi, C, Cassese, E, De Rosa, M, Schiraldi, C
Advances in therapy. 2019;(11):3221-3237
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INTRODUCTION Oral supplementation of chondroitin sulfate (CS) and glucosamine (GlcN), symptomatic slow-acting molecules, is recommended by European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis and Musculoskeletal Diseases (ESCEO) and other European Union (EU) guidelines for the restoration of the articular cartilage surface in patients affected by osteoarthritis (OA). They are commercialized as pharmaceutical grade products and as food supplements in combination with plant extracts hyaluronic acid, methylsulfonylmethane, and other components. Food supplements do not need to undergo the strict regulatory controls of pharmaceutical grade products; thus, composition and contaminants that could be present may not be evidenced before commercialization and these uncertainties may give rise to concerns about the bioactivity of these formulations. METHODS In this paper 10 different food supplements (FS) from diverse European countries were analyzed in comparison with two pharmaceutical grade products (Ph) using updated analytical approaches and biochemical cell-based assays. The purity, the titer, and the origin of CS in Ph and FS samples were initially assessed in order to successively compare the biological function. Both food supplements and pharmaceutical formulations were tested in vitro, using the same final CS concentration, on primary chondrocytes and synoviocytes in terms of (i) cell viability, (ii) activation of the NF-κB-mediated inflammation pathway, (iii) cartilage oligomeric matrix protein (COMP-2), IL-6, and IL-8 production. RESULTS All the FS presented a certain insoluble fraction; the CS and the GlcN contents were lower than the declared ones in 9/10 and 8/10 samples, respectively. All FS contained keratan sulfate (KS) at up to 50% of the total glycosaminoglycan amount declared on the label. Primary cells treated with the samples diluted to present the same CS concentration in the medium showed cytotoxicity in 7/10 FS while Ph preserved viability and reduced NF-κB, COMP-2, and secreted inflammatory cytokines. CONCLUSION Among all samples tested, the pharmaceutical grade products demonstrated effective modulation of biomarkers counteracting the inflammation status and improving viability and the physiological condition of OA human primary chondrocyte and synoviocyte cells. In contrast to that, most FS were cytotoxic at the tested concentrations, and only 3/10 of them showed similarities to Ph sample behavior in vitro. FUNDING This work was partially supported by PON01_1226 NUTRAFAST, MIUR Ministero dell'Università e della Ricerca Scientifica. Bioteknet financed two short-term grants for graduate technicians. The journal's Rapid Service and Open Access fees were funded by IBSA CH.
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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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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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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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Safety of Symptomatic Slow-Acting Drugs for Osteoarthritis: Outcomes of a Systematic Review and Meta-Analysis.
Honvo, G, Reginster, JY, Rabenda, V, Geerinck, A, Mkinsi, O, Charles, A, Rizzoli, R, Cooper, C, Avouac, B, Bruyère, O
Drugs & aging. 2019;(Suppl 1):65-99
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BACKGROUND Symptomatic slow-acting drugs for osteoarthritis (SYSADOAs) are an important drug class in the treatment armamentarium for osteoarthritis (OA). OBJECTIVE We aimed to re-assess the safety of various SYSADOAs in a comprehensive meta-analysis of randomized placebo-controlled trials, using, as much as possible, data from full safety reports. METHODS We performed a systematic review and random-effects meta-analyses of randomized, double-blind, placebo-controlled trials that assessed adverse events (AEs) with various SYSADOAs in patients with OA. The databases MEDLINE, Cochrane Central Register of Controlled Trials (Ovid CENTRAL) and Scopus were searched. The primary outcomes were overall severe and serious AEs, as well as AEs involving the following Medical Dictionary for Regulatory Activities (MedDRA) system organ classes (SOCs): gastrointestinal, cardiac, vascular, nervous system, skin and subcutaneous tissue, musculoskeletal and connective tissue, renal and urinary system. RESULTS Database searches initially identified 3815 records. After exclusions according to the selection criteria, 25 studies on various SYSADOAs were included in the qualitative synthesis, and 13 studies with adequate data were included in the meta-analyses. Next, from the studies previously excluded according to the protocol, 37 with mainly oral nonsteroidal anti-inflammatory drugs (NSAIDs) permitted as concomitant medication were included in a parallel qualitative synthesis, from which 18 studies on various SYSADOAs were included in parallel meta-analyses. This post hoc parallel inclusion was conducted because of the high number of studies allowing concomitant anti-OA medications. Indeed, primarily excluding studies with concomitant anti-OA medications was crucial for a meta-analysis on safety. The decision for parallel inclusion was made for the purpose of comparative analyses. Glucosamine sulfate (GS), chondroitin sulfate (CS) and avocado soybean unsaponifiables (ASU; Piascledine®) were not associated with increased odds for any type of AEs compared with placebo. Overall, with/without concomitant OA medication, diacerein was associated with significantly increased odds of total AEs (odds ratio [OR] 2.22; 95% confidence interval [CI] 1.58-3.13; I2 = 52.8%), gastrointestinal disorders (OR 2.85; 95% CI 2.02-4.04; I2 = 62.8%) and renal and urinary disorders (OR 3.42; 95% CI 2.36-4.96; I2 = 17.0%) compared with placebo. In studies that allowed concomitant OA medications, diacerein was associated with significantly more dermatological disorders (OR 2.47; 95% CI 1.42-4.31; I2 = 0%) and more dropouts due to AEs (OR 3.18; 95% CI 1.85-5.47; I2 = 13.4%) than was placebo. No significant increase in serious or severe AEs was found with diacerein versus placebo. CONCLUSIONS GS and CS can be considered safe treatments for patients with OA. All eligible studies on ASU included in our analysis used the proprietary product Piascledine® and allowed other anti-OA medications; thus, the safety of ASU must be confirmed in future studies without concomitant anti-OA medications. Given the safety concerns with diacerein, its usefulness in patients with OA should be assessed, taking into account individual patient characteristics.
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Consensus recommendations for managing osteoarthritic pain with topical NSAIDs in Asia-Pacific.
Rafanan, BS, Valdecañas, BF, Lim, BP, Malairungsakul, A, Tassanawipas, W, Shiyi, C, Tse, LF, Luong, TK
Pain management. 2018;(2):115-128
Abstract
Osteoarthritis prevalence is expected to increase markedly in the Asia-Pacific region due to rapid population aging. Identifying effective and safe therapeutic options to manage osteoarthritic pain is viewed as a priority. The Asia-Pacific Experts on Topical Analgesics Advisory Board developed consensus statements for use of topical NSAIDs in musculoskeletal pain. Evidence supporting these statements in osteoarthritic pain was reviewed. Best available evidence indicates that topical NSAIDs have a moderate effect on relief of osteoarthritic pain, comparable to that of oral NSAIDs but with a better risk-to-benefit ratio. International clinical practice guidelines recommend topical NSAIDs on par with or ahead of oral NSAIDs for pain management in patients with knee and hand osteoarthritis, and as the first-line choice in persons aged ≥75 years.