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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.
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[Cartilage/chondrocyte research and osteoarthritis. Mechanobiology for development of osteoarthritis.].
Ogawa, H, Akiyama, H
Clinical calcium. 2018;(6):789-795
Abstract
Articular cartilage is exquisitely sensitive to their mechanical environment, and mechanical loading may be the most important external factor regulating cartilage metabolism. Mechanical loading regulates chondrocyte activity, and pathological excessive loading leads to abnormal mechanotransduction, which in turn induces cartilage degradation. Several studies report that moderate levels of exercise exerts beneficial effects, such as improvements in pain and physical function, and also mitigates joint destruction through the down-regulation of the expression of matrix proteases. Calcium signaling is an initial step in chondrocyte mechanotransduction that has been linked to many cellular processes, and recent studies found that calcium ion channels distinctively mechanically activated by physiological or pathological mechanical loading through transient receptor potential vanilloid 4(TRPV4)or Piezo ion channels. We review here the recent progress on mechanotransduction of chondocytes, highlighting the calcium ion channels.
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Calcium-Containing Crystals and Osteoarthritis: an Unhealthy Alliance.
Conway, R, McCarthy, GM
Current rheumatology reports. 2018;(3):13
Abstract
PURPOSE OF REVIEW Osteoarthritis (OA) is the most common form of joint disease globally and is associated with significant morbidity and disability. Increasing evidence points to an important inflammatory component in the development and progression of OA. The precise pathways involved in OA inflammatory processes remain to be clarified. Basic calcium phosphate (BCP) and calcium pyrophosphate dihydrate (CPP) crystals can induce inflammation and arthritis and recent studies point to a potential pathogenic role in OA. In the light of this evidence, we explore the relationship and potential mechanistic pathways linking calcium-containing crystals and OA. RECENT FINDINGS CPP crystals induce inflammation through the NLRP3 inflammasome while BCP crystals mediate both NLRP3 dependent and independent effects. BCP crystals have been demonstrated to induce key mitogenic and inflammatory pathways and contribute to cartilage degradation. Calcium-containing crystals induce key inflammatory pathways and may represent an attractive novel target in OA, a condition devoid of effective treatments.
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4.
Role of Fat-Soluble Vitamins in Osteoarthritis Management.
Zheng, XY, Liang, J, Li, YS, Tu, M
Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases. 2018;(3):132-137
Abstract
Osteoarthritis (OA) is a chronic degenerative joint disease, in which metabolic imbalance in bone is observed. The pathological mechanism of metabolic imbalance is not clear yet, but the nutritional factors, particularly the vitamins, might be intrinsic to the development and progression of OA. In this review article, we have explored databases such as PubMed, Scopus, and Google Scholar articles until the beginning of 2017 and reviewed the role of fat-soluble vitamins in pathological and therapeutic aspects of OA. Vitamin D plays an important role in the development and maintenance of the skeleton, as well as bone and cartilage metabolism, and its deficiency is implicated in the pathological process of OA. Vitamin E enhances chondrocyte growth and exhibits an anti-inflammatory activity, as well as plays an important role in the prevention of cartilage degeneration. In human OA cartilage, vitamin K deficiency produces abnormal growth plate calcification and inappropriate mineralization of cartilage. Thus, these fat-soluble vitamins play a key role in the pathophysiology of OA, and supplementation of these vitamins may provide innovative approaches for OA management. However, vitamin A has a different role, which is a regulator of cartilage and skeletal formation. When metabolite levels of vitamin A are elevated in synovial fluid, they appear to drive OA development. The role of inhibitors of vitamin A here remains unclear. More investigations are needed to examine the effects of fat-soluble vitamins on the various molecular pathways of OA, as well as to assess the efficacy and safety of their usage clinically.
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5.
Natural Products for Promoting Joint Health and Managing Osteoarthritis.
Henrotin, Y, Mobasheri, A
Current rheumatology reports. 2018;(11):72
Abstract
PURPOSE OF REVIEW Osteoarthritis, the most common joint disease, is associated with substantial medical costs, lost productivity, and reduced quality of life. However, available pharmaceutical treatments have limitations in terms of efficacy and long-term safety. RECENT FINDINGS In vitro evidence suggests that some natural products may possess anti-inflammatory and anti-oxidative properties and may inhibit the release of key osteoarthritis-related cytokines. There is, therefore, ongoing interest in identifying natural products that safely promote joint health and treat osteoarthritis. Numerous plant extracts, including curcumin, Boswellia extract, and pycnogenol, have shown effect sizes (ES) for reducing pain and functional disability larger than those observed with analgesics and products such as glucosamine and chondroitin. The ES for methylsulfonylmethane and avocado/soybean unsaponifiables are also considered to be clinically relevant. Data from a small number of studies using natural products for treating osteoarthritis are promising but require confirmation in further well-designed clinical trials.
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6.
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.
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7.
Metabolomics of osteoarthritis: emerging novel markers and their potential clinical utility.
Zhai, G, Randell, EW, Rahman, P
Rheumatology (Oxford, England). 2018;(12):2087-2095
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Abstract
OA is a multifactorial and progressive disease with no cure yet. Substantial efforts have been made and several biochemical and genetic markers have been reported, but neither alone nor in combination is adequate to identify early OA changes or determine disease progression with sufficient predictive values. Recent advances in metabolomics and its application to the study of OA have led to elucidation of involvement of several metabolic pathways and new specific metabolic markers for OA. Some of these metabolic pathways affect amino acid metabolism, including branched chain amino acids and arginine, and phospholipid metabolism involving conversion of phosphatidylcholine to lysophosphatidylcholine. These metabolic markers appear to be clinically actionable and may potentially improve the clinical management of OA patients. In this article, we review the recent studies of metabolomics of OA, discuss those novel metabolic markers and their potential clinical utility, and indicate future research directions in the field.
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Potentials and Limits of Physiotherapy in Osteoarthritis.
Richter, K, Muller-Ladner, U, Dischereit, G, Uwe, L
Current rheumatology reviews. 2018;(2):117-122
Abstract
BACKGROUND In view of the already existing and the expected growing costs due to the pathological osteoarthritic joint alterations and the related consequences, preventive and conservative strategies which can avoid or delay osteoarthritic joint alterations are welcomed from a socioeconomical perspective. Here, it should be mentioned that corresponding primary prevention measures should take place early by already educating children about a healthy diet and motivating them to regular physical exercise. In overt or symptomatic osteoarthritis, a good joint function and reduction of disease-related pain as well as a delay in the progression of osteoarthritis should be the primary goals of non-surgical therapeutic approaches. OBJECTIVE The current body of studies is already able to prove the effectiveness of differential indicative physiotherapeutic and physical measures and should be further developed in the future. Nevertheless, the implementation of the available knowledge from the studies under evidencebased medicine criteria proves difficult during the daily routine in clinics. On one hand, an assessment of the effectiveness of physical therapy within the framework of a multimodal treatment approach (e.g. thermotherapy in combination with manual therapy) is difficult to define. RESULT AND CONCLUSION On the other hand, an objective assessment of treatment success, owing to the heterogeneity among the patients (above all varied disease activity, functional limitations, accompanying diseases and therapy) will also remain complicated.
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Which supplements can I recommend to my osteoarthritis patients?
Liu, X, Eyles, J, McLachlan, AJ, Mobasheri, A
Rheumatology (Oxford, England). 2018;(suppl_4):iv75-iv87
Abstract
OA is a chronic and disabling joint disease with limited evidence-based pharmacological treatment options available that improve outcomes for patients safely. Faced with few effective pharmacological treatments, the use has grown of dietary supplements and complementary medicines for symptomatic relief among people living with OA. The aim of this review is to provide a summary of existing evidence and recommendations supporting the use of supplements for OA. Systematic reviews and randomized controlled trials investigating oral supplements for treating OA were identified. Limited research evidence supports recommendations for the oral use of Boswellia serrata extract and Pycnogenol, curcumin and methylsulfonylmethane in people with OA despite the poor quality of the available studies. Few studies adequately reported possible adverse effects related to supplementation, although the products were generally recognized as safe. Further high quality trials are needed to improve the strength of evidence to support this recommendation and better guide optimal treatment of people living with OA.
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10.
Epigenetics of Skeletal Diseases.
Del Real, A, Riancho-Zarrabeitia, L, López-Delgado, L, Riancho, JA
Current osteoporosis reports. 2018;(3):246-255
Abstract
PURPOSE OF REVIEW Epigenetic mechanisms modify gene activity in a stable manner without altering DNA sequence. They participate in the adaptation to the environment, as well as in the pathogenesis of common complex disorders. We provide an overview of the role of epigenetic mechanisms in bone biology and pathology. RECENT FINDINGS Extensive evidence supports the involvement of epigenetic mechanisms (DNA methylation, post-translational modifications of histone tails, and non-coding RNAs) in the differentiation of bone cells and mechanotransduction. A variety of epigenetic abnormalities have been described in patients with osteoporosis, osteoarthritis, and skeletal cancers, but their actual pathogenetic roles are still unclear. A few drugs targeting epigenetic marks have been approved for neoplastic disorders, and many more are being actively investigated. Advances in the field of epigenetics underscore the complex interactions between genetic and environmental factors as determinants of osteoporosis and other common disorders. Likewise, they help to explain the mechanisms by which prenatal and post-natal external factors, from nutrition to psychological stress, impact our body and influence the risk of later disease.