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      The spice for joint inflammation: anti-inflammatory role of curcumin in treating osteoarthritis

      Drug Design, Development and Therapy

      Dove Medical Press

      cartilage, chondrocyte, Curcuma, inflammation, joint, pain

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          Abstract

          Osteoarthritis is a degenerative disease of the joint affecting aging populations worldwide. It has an underlying inflammatory cause, which contributes to the loss of chondrocytes, leading to diminished cartilage layer at the affected joints. Compounds with anti-inflammatory properties are potential treatment agents for osteoarthritis. Curcumin derived from Curcuma species is an anti-inflammatory compound as such. This review aims to summarize the antiosteoarthritic effects of curcumin derived from clinical and preclinical studies. Many clinical trials have been conducted to determine the effectiveness of curcumin in osteoarthritic patients. Extracts of Curcuma species, curcuminoids and enhanced curcumin, were used in these studies. Patients with osteoarthritis showed improvement in pain, physical function, and quality of life after taking curcumin. They also reported reduced concomitant usage of analgesics and side effects during treatment. In vitro studies demonstrated that curcumin could prevent the apoptosis of chondrocytes, suppress the release of proteoglycans and metal metalloproteases and expression of cyclooxygenase, prostaglandin E-2, and inflammatory cytokines in chondrocytes. These were achieved by blocking the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) system in the chondrocytes, by preventing the activation of nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha, phosphorylation, and translocation of the p65 subunit of NF-κB complexes into the nucleus. In conclusion, curcumin is a potential candidate for the treatment of osteoarthritis. More well-planned randomized control trials and enhanced curcumin formulation are required to justify the use of curcumin in treating osteoarthritis.

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          Most cited references 40

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          OARSI recommendations for the management of hip and knee osteoarthritis, Part II: OARSI evidence-based, expert consensus guidelines.

          To develop concise, patient-focussed, up to date, evidence-based, expert consensus recommendations for the management of hip and knee osteoarthritis (OA), which are adaptable and designed to assist physicians and allied health care professionals in general and specialist practise throughout the world. Sixteen experts from four medical disciplines (primary care, rheumatology, orthopaedics and evidence-based medicine), two continents and six countries (USA, UK, France, Netherlands, Sweden and Canada) formed the guidelines development team. A systematic review of existing guidelines for the management of hip and knee OA published between 1945 and January 2006 was undertaken using the validated appraisal of guidelines research and evaluation (AGREE) instrument. A core set of management modalities was generated based on the agreement between guidelines. Evidence before 2002 was based on a systematic review conducted by European League Against Rheumatism and evidence after 2002 was updated using MEDLINE, EMBASE, CINAHL, AMED, the Cochrane Library and HTA reports. The quality of evidence was evaluated, and where possible, effect size (ES), number needed to treat, relative risk or odds ratio and cost per quality-adjusted life years gained were estimated. Consensus recommendations were produced following a Delphi exercise and the strength of recommendation (SOR) for propositions relating to each modality was determined using a visual analogue scale. Twenty-three treatment guidelines for the management of hip and knee OA were identified from the literature search, including six opinion-based, five evidence-based and 12 based on both expert opinion and research evidence. Twenty out of 51 treatment modalities addressed by these guidelines were universally recommended. ES for pain relief varied from treatment to treatment. Overall there was no statistically significant difference between non-pharmacological therapies [0.25, 95% confidence interval (CI) 0.16, 0.34] and pharmacological therapies (ES=0.39, 95% CI 0.31, 0.47). Following feedback from Osteoarthritis Research International members on the draft guidelines and six Delphi rounds consensus was reached on 25 carefully worded recommendations. Optimal management of patients with OA hip or knee requires a combination of non-pharmacological and pharmacological modalities of therapy. Recommendations cover the use of 12 non-pharmacological modalities: education and self-management, regular telephone contact, referral to a physical therapist, aerobic, muscle strengthening and water-based exercises, weight reduction, walking aids, knee braces, footwear and insoles, thermal modalities, transcutaneous electrical nerve stimulation and acupuncture. Eight recommendations cover pharmacological modalities of treatment including acetaminophen, cyclooxygenase-2 (COX-2) non-selective and selective oral non-steroidal anti-inflammatory drugs (NSAIDs), topical NSAIDs and capsaicin, intra-articular injections of corticosteroids and hyaluronates, glucosamine and/or chondroitin sulphate for symptom relief; glucosamine sulphate, chondroitin sulphate and diacerein for possible structure-modifying effects and the use of opioid analgesics for the treatment of refractory pain. There are recommendations covering five surgical modalities: total joint replacements, unicompartmental knee replacement, osteotomy and joint preserving surgical procedures; joint lavage and arthroscopic debridement in knee OA, and joint fusion as a salvage procedure when joint replacement had failed. Strengths of recommendation and 95% CIs are provided. Twenty-five carefully worded recommendations have been generated based on a critical appraisal of existing guidelines, a systematic review of research evidence and the consensus opinions of an international, multidisciplinary group of experts. The recommendations may be adapted for use in different countries or regions according to the availability of treatment modalities and SOR for each modality of therapy. These recommendations will be revised regularly following systematic review of new research evidence as this becomes available.
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            OARSI recommendations for the management of hip and knee osteoarthritis, part I: critical appraisal of existing treatment guidelines and systematic review of current research evidence.

            As a prelude to developing updated, evidence-based, international consensus recommendations for the management of hip and knee osteoarthritis (OA), the Osteoarthritis Research Society International (OARSI) Treatment Guidelines Committee undertook a critical appraisal of published guidelines and a systematic review (SR) of more recent evidence for relevant therapies. Sixteen experts from four medical disciplines (primary care two, rheumatology 11, orthopaedics one and evidence-based medicine two), two continents and six countries (USA, UK, France, Netherlands, Sweden and Canada) formed the guidelines development team. Three additional experts were invited to take part in the critical appraisal of existing guidelines in languages other than English. MEDLINE, EMBASE, Science Citation Index, CINAHL, AMED, Cochrane Library, seven Guidelines Websites and Google were searched systematically to identify guidelines for the management of hip and/or knee OA. Guidelines which met the inclusion/exclusion criteria were assigned to four groups of four appraisers. The quality of the guidelines was assessed using the AGREE (Appraisal of Guidelines for Research and Evaluation) instrument and standardised percent scores (0-100%) for scope, stakeholder involvement, rigour, clarity, applicability and editorial independence, as well as overall quality, were calculated. Treatment modalities addressed and recommended by the guidelines were summarised. Agreement (%) was estimated and the best level of evidence to support each recommendation was extracted. Evidence for each treatment modality was updated from the date of the last SR in January 2002 to January 2006. The quality of evidence was evaluated using the Oxman and Guyatt, and Jadad scales for SRs and randomised controlled trials (RCTs), respectively. Where possible, effect size (ES), number needed to treat, relative risk (RR) or odds ratio and cost per quality-adjusted life year gained (QALY) were estimated. Twenty-three of 1462 guidelines or consensus statements retrieved from the literature search met the inclusion/exclusion criteria. Six were predominantly based on expert opinion, five were primarily evidence based and 12 were based on both. Overall quality scores were 28%, 41% and 51% for opinion-based, evidence-based and hybrid guidelines, respectively (P=0.001). Scores for aspects of quality varied from 18% for applicability to 67% for scope. Thirteen guidelines had been developed for specific care settings including five for primary care (e.g., Prodigy Guidance), three for rheumatology (e.g., European League against Rheumatism recommendations), three for physiotherapy (e.g., Dutch clinical practice guidelines for physical therapy) and two for orthopaedics (e.g., National Institutes of Health consensus guidelines), whereas 10 did not specify the target users (e.g., Ontario guidelines for optimal therapy). Whilst 14 guidelines did not separate hip and knee, eight were specific for knee but only one for hip. Fifty-one different treatment modalities were addressed by these guidelines, but only 20 were universally recommended. Evidence to support these modalities ranged from Ia (meta-analysis/SR of RCTs) to IV (expert opinion). The efficacy of some modalities of therapy was confirmed by the results of RCTs published between January 2002 and 2006. These included exercise (strengthening ES 0.32, 95% confidence interval (CI) 0.23, 0.42, aerobic ES 0.52, 95% CI 0.34, 0.70 and water-based ES 0.25, 95% CI 0.02, 0.47) and nonsteroidal anti-inflammatory drugs (NSAIDs) (ES 0.32, 95% CI 0.24, 0.39). Examples of other treatment modalities where recent trials failed to confirm efficacy included ultrasound (ES 0.06, 95% CI -0.39, 0.52), massage (ES 0.10, 95% CI -0.23, 0.43) and heat/ice therapy (ES 0.69, 95% CI -0.07, 1.45). The updated evidence on adverse effects also varied from treatment to treatment. For example, while the evidence for gastrointestinal (GI) toxicity of non-selective NSAIDs (RR=5.36, 95% CI 1.79, 16.10) and for increased risk of myocardial infarction associated with rofecoxib (RR=2.24, 95% CI 1.24, 4.02) were reinforced, evidence for other potential drug related adverse events such as GI toxicity with acetaminophen or myocardial infarction with celecoxib remained inconclusive. Twenty-three guidelines have been developed for the treatment of hip and/or knee OA, based on opinion alone, research evidence or both. Twenty of 51 modalities of therapy are universally recommended by these guidelines. Although this suggests that a core set of recommendations for treatment exists, critical appraisal shows that the overall quality of existing guidelines is sub-optimal, and consensus recommendations are not always supported by the best available evidence. Guidelines of optimal quality are most likely to be achieved by combining research evidence with expert consensus and by paying due attention to issues such as editorial independence, stakeholder involvement and applicability. This review of existing guidelines provides support for the development of new guidelines cognisant of the limitations in existing guidelines. Recommendations should be revised regularly following SR of new research evidence as this becomes available.
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              Prevalence of knee osteoarthritis in the United States: arthritis data from the Third National Health and Nutrition Examination Survey 1991-94.

              To estimate the US national prevalence of tibiofemoral radiographic knee osteoarthritis (RKOA) with and without symptoms, and its influence on functional tasks. Radiographic and interview data from the National Health and Nutrition Examination Survey (NHANES III), a nationally representative cross-sectional health examination survey, were used to estimate lifetime RKOA prevalence in adults age 60 years and older. Demographic trends, self-reported activity limitations, physical performance test results, and patterns of recent analgesic use were analyzed. Among US adults, the prevalence of RKOA and symptomatic RKOA was 37.4% and 12.1%, respectively. RKOA prevalence was greater among women than men (42.1% vs 31.2%). Women had significantly more Kellgren-Lawrence Grade 3-4 changes (12.9% vs 6.5% in men). However, symptomatic RKOA prevalence did not differ by sex. Additionally, some 1.6% of US adults had knee joint replacement. Multivariable analysis showed significantly higher odds of both RKOA and symptomatic RKOA with greater body mass index (BMI > or = 30), greater age, non-Hispanic Black race/ethnicity, and among men with manual labor occupations. Only symptomatic RKOA was significantly associated with self-reported activity limitations: difficulty walking, stooping, standing from a seated position, and stair climbing. Adults with symptomatic RKOA used significantly more assistive walking devices, had slower measured gait velocities, and used significantly more prescription nonsteroidal antiinflammatory drugs and prescription narcotics, and nonprescription acetaminophen. NHANES III data provide an overall national assessment of the prevalence, demographic distributions, and functional impact of symptomatic knee OA, which affects more than 1 in 10, or 4.3 million older US adults.
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                Author and article information

                Journal
                Drug Des Devel Ther
                Drug Des Devel Ther
                Drug Design, Development and Therapy
                Drug Design, Development and Therapy
                Dove Medical Press
                1177-8881
                2016
                20 September 2016
                : 10
                : 3029-3042
                Affiliations
                Department of Pharmacology, Universiti Kebangsaan Malaysia Medical Centre, Cheras, Malaysia
                Author notes
                Correspondence: Kok-Yong Chin, Department of Pharmacology, Level 17, Preclinical Building, Universiti Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif, Bandar Tun Razak, 56000 Cheras, Kuala Lumpur, Malaysia, Tel +60 3 9145 9573, Email chinkokyong@ 123456ppukm.ukm.edu.my
                Article
                dddt-10-3029
                10.2147/DDDT.S117432
                5036591
                © 2016 Chin. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                Categories
                Review

                Pharmacology & Pharmaceutical medicine

                pain, joint, inflammation, curcuma, chondrocyte, cartilage

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