{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T23:38:54Z","timestamp":1793835534646,"version":"4.6.1"},"reference-count":30,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,7,27]],"date-time":"2019-07-27T00:00:00Z","timestamp":1564185600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2019,7,27]],"date-time":"2019-07-27T00:00:00Z","timestamp":1564185600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Arthritis Res Ther"],"published-print":{"date-parts":[[2019,12]]},"DOI":"10.1186\/s13075-019-1960-5","type":"journal-article","created":{"date-parts":[[2019,7,27]],"date-time":"2019-07-27T13:02:36Z","timestamp":1564232556000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":90,"title":["Bio-optimized Curcuma longa extract is efficient on knee osteoarthritis pain: a double-blind multicenter randomized placebo controlled three-arm study"],"prefix":"10.1186","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2846-4398","authenticated-orcid":false,"given":"Y.","family":"Henrotin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Malaise","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Wittoek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"de Vlam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.-P.","family":"Brasseur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F. P.","family":"Luyten","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Q.","family":"Jiangang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Van den Berghe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Uhoda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Bentin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"De Vroey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Erpicum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. F.","family":"Donneau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y.","family":"Dierckxsens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,7,27]]},"reference":[{"key":"1960_CR1","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1016\/j.joca.2017.11.014","volume":"26","author":"AE Nelson","year":"2018","unstructured":"Nelson AE. Osteoarthritis year in review 2017: clinical. Osteoarthritis Cartilage. 2018;26:319\u201325.","journal-title":"Osteoarthritis Cartilage"},{"key":"1960_CR2","doi-asserted-by":"publisher","first-page":"16072","DOI":"10.1038\/nrdp.2016.72","volume":"2","author":"J Martel-Pelletier","year":"2016","unstructured":"Martel-Pelletier J, Barr AJ, Cicuttini FM, et al. Osteoarthritis. Nat Rev Dis Primers. 2016;2:16072.","journal-title":"Nat Rev Dis Primers"},{"issue":"6","key":"1960_CR3","doi-asserted-by":"publisher","first-page":"1821","DOI":"10.1093\/ije\/dyy187","volume":"47","author":"Angelico Mendy","year":"2018","unstructured":"Mendy A, Park J, Vieira ER. Osteoarthritis and risk of mortality in the USA: a population-based cohort study. Int J Epidemiol. 2018;10. \nhttps:\/\/doi.org\/10.1093\/ije\/dyy187\n\n.","journal-title":"International Journal of Epidemiology"},{"key":"1960_CR4","doi-asserted-by":"publisher","first-page":"476","DOI":"10.1016\/j.joca.2010.01.013","volume":"18","author":"W Zhang","year":"2010","unstructured":"Zhang W, Nuki G, Moskowitz RW, et al. OARSI recommendations for the management of hip and knee osteoarthritis: part III: changes in evidence following systematic cumulative update of research published through January 2009. Osteoarthr Cartil. 2010;18:476\u201399.","journal-title":"Osteoarthr Cartil"},{"key":"1960_CR5","doi-asserted-by":"publisher","first-page":"1145","DOI":"10.1136\/ard.2003.011742","volume":"62","author":"KM Jordan","year":"2003","unstructured":"Jordan KM, Arden NK, Doherty M, et al. Standing Committee for International Clinical Studies Including Therapeutic Trials ESCISIT. EULAR recommendations: an evidence-based approach to the management of knee osteoarthritis: Report of a Task Force of the Standing Committee for International Clinical Studies Including Therapeutic Trials (ESCISIT). Ann Rheum Dis. 2003;62:1145\u201355.","journal-title":"Ann Rheum Dis"},{"issue":"1","key":"1960_CR6","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1136\/ard.2007.084772","volume":"68","author":"W Zhang","year":"2009","unstructured":"Zhang W, Doherty M, Leeb BF, Alekseeva L, Arden NK, Bijlsma JW, Dincer F, Dziedzic K, Hauselmann HJ, Kaklamanis P, Kloppenburg M, Lohmander LS, Maheu E, Martin-Mola E, Pavelka K. Punzi EULAR evidence-based recommendations for the diagnosis of hand osteoarthritis: report of a task force of ESCISIT. Ann Rheum Dis. 2009;68(1):8\u201317.","journal-title":"Ann Rheum Dis"},{"key":"1960_CR7","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1016\/j.joca.2014.01.003","volume":"22","author":"TE McAlindon","year":"2014","unstructured":"McAlindon TE, Bannuru RR, Sullivan MC, et al. OARSI guidelines for the non-surgical management of knee osteoarthritis. Osteoarthr Cartil. 2014;22:363\u201388.","journal-title":"Osteoarthr Cartil"},{"key":"1960_CR8","doi-asserted-by":"publisher","first-page":"1534","DOI":"10.1136\/ard.2011.154047","volume":"70","author":"M Doherty","year":"2011","unstructured":"Doherty M, Hawkey C, Goulder M, Gibb I, Hill N, Aspley S, Reader S. A randomised controlled trial of ibuprofen, paracetamol or a combination tablet of ibuprofen\/paracetamol in community-derived people with knee pain. Ann Rheum Dis. 2011;70:1534\u201341.","journal-title":"Ann Rheum Dis"},{"key":"1960_CR9","doi-asserted-by":"publisher","first-page":"h1225","DOI":"10.1136\/bmj.h1225","volume":"350","author":"GC Machado","year":"2015","unstructured":"Machado GC, Maher CG, Ferreira PH, et al. Efficacy and safety of paracetamol for spinal pain and osteoarthritis: systematic review and meta-analysis of randomised placebo-controlled trials. BMJ. 2015;350:h1225. \nhttps:\/\/doi.org\/10.1136\/bmj.h1225\n\n.","journal-title":"BMJ"},{"key":"1960_CR10","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1016\/j.ejim.2015.03.008","volume":"26","author":"P Ungprasert","year":"2015","unstructured":"Ungprasert P, Cheungpasitporn W, Crowson CS, Matteson EL. Individual non-steroidal anti-inflammatory drugs and risk of acute kidney injury: a systematic review and meta-analysis of observational studies. Eur J Intern Med. 2015;26:285\u201391.","journal-title":"Eur J Intern Med"},{"key":"1960_CR11","doi-asserted-by":"publisher","first-page":"769","DOI":"10.1016\/S0140-6736(13)60900-9","volume":"382","author":"N Bhala","year":"2013","unstructured":"Coxib and traditional NSAID Trialists\u2019 (CNT) Collaboration, Bhala N, Emberson J, Merhi A, et al. Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analyses of individual participant data from randomised trials. Lancet. 2013;382:769\u201379.","journal-title":"Lancet"},{"key":"1960_CR12","doi-asserted-by":"publisher","first-page":"2093","DOI":"10.1016\/S0140-6736(16)30002-2","volume":"387","author":"B da Costa","year":"2016","unstructured":"da Costa B, Keichenbach S, Keller N, et al. Effectiveness of non-steroidal antiinflammatory drugs for the treatment of pain in knee and hip osteoarthritis: a network meta-analysis. Lancet. 2016;387:2093\u2013105.","journal-title":"Lancet"},{"key":"1960_CR13","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1002\/acr.21596","volume":"64","author":"MC Hochberg","year":"2012","unstructured":"Hochberg MC, Altman RD, April KT, et al. American College of Rheumatology 2012 recommendations for the use of nonpharmacologic and pharmacologic therapies in osteoarthritis of the hand, hip, and knee. Arthritis Care Res. 2012;64:465\u201374.","journal-title":"Arthritis Care Res"},{"issue":"4","key":"1960_CR14","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1186\/ar2016","volume":"8","author":"LG Ameye","year":"2006","unstructured":"Ameye LG, Chee WS. Osteoarthritis and nutrition. From nutraceuticals to functional foods: a systematic review of the scientific evidence. Arthritis Res Ther. 2006;8(4):127\u201335.","journal-title":"Arthritis Res Ther"},{"key":"1960_CR15","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.joca.2010.10.017","volume":"19","author":"Y Henrotin","year":"2011","unstructured":"Henrotin Y, Lambert C, Couchourel D, Ripoll C, Chiotelli E. Nutraceuticals: do they represent a new era in the management of osteoarthritis? A narrative review from the lessons taken with five products. Osteoarthr Cartil. 2011;19:1\u201321.","journal-title":"Osteoarthr Cartil"},{"key":"1960_CR16","doi-asserted-by":"publisher","first-page":"899","DOI":"10.1007\/s00011-009-0063-1","volume":"58","author":"M Mathy-Hartert","year":"2009","unstructured":"Mathy-Hartert M, Jacquemond-Collet I, Priem F, Sanchez C, Lambert C, Henrotin Y. Curcumin inhibits pro-inflammatory mediators and metalloproteinase-3 production by chondrocytes. Inflamm Res. 2009;58:899\u2013908.","journal-title":"Inflamm Res"},{"key":"1960_CR17","doi-asserted-by":"publisher","first-page":"1837","DOI":"10.3892\/mmr.2017.6771","volume":"16","author":"J Wang","year":"2017","unstructured":"Wang J, Ma J, Gu JH, Wang FY, Shang XS, Tao HR, Wang X. Regulation of type II collagen, matrix metalloproteinase-13 and cell proliferation by interleukin-1\u03b2 is mediated by curcumin via inhibition of NF-\u03baB signaling in rat chondrocytes. Mol Med Rep. 2017;16:1837\u201345.","journal-title":"Mol Med Rep"},{"key":"1960_CR18","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1016\/j.molmed.2012.01.004","volume":"18","author":"L Shen","year":"2012","unstructured":"Shen L, Ji HF. The pharmacology of curcumin: is it the degradation products? Trends Mol Med. 2012;18:138\u201344.","journal-title":"Trends Mol Med"},{"issue":"32","key":"1960_CR19","doi-asserted-by":"publisher","first-page":"28556","DOI":"10.1074\/jbc.M111.256180","volume":"286","author":"C Buhrmann","year":"2011","unstructured":"Buhrmann C, Mobasheri A, Busch F, Aldinger C, Stahlmann R, Montaseri A, Shakibaei M. Curcumin modulates nuclear factor kappaB (NF-kappaB)-mediated inflammation in human tenocytes in vitro: role of the phosphatidylinositol 3-kinase\/Akt pathway. J Biol Chem. 2011;286(32):28556\u201366.","journal-title":"J Biol Chem"},{"key":"1960_CR20","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1136\/bjsports-2016-097333","volume":"52","author":"X Liu","year":"2018","unstructured":"Liu X, Machado GC, Eyles JP, Ravi V, Hunter DJ. Dietary supplements for treating osteoarthritis: a systematic review and meta-analysis. Br J Sports Med. 2018;52:167\u201375.","journal-title":"Br J Sports Med"},{"issue":"3","key":"1960_CR21","doi-asserted-by":"publisher","first-page":"416","DOI":"10.1016\/j.semarthrit.2018.03.001","volume":"48","author":"Raveendhara R. Bannuru","year":"2018","unstructured":"Bannuru RR, Osani MC, Al-Eid F, Wang C. Efficacy of curcumin and Boswellia for knee osteoarthritis: systematic review and meta-analysis. Semin Arthritis Rheum. 2018;48(3):416-29.","journal-title":"Seminars in Arthritis and Rheumatism"},{"key":"1960_CR22","first-page":"1192","volume":"17","author":"A Sahebkar","year":"2016","unstructured":"Sahebkar A, Henrotin Y. Analgesic efficacy and safety of curcuminoids in clinical practice: a systematic review and meta-analysis of randomized controlled trials. Pain Med. 2016;17:1192\u2013202.","journal-title":"Pain Med"},{"key":"1960_CR23","doi-asserted-by":"publisher","first-page":"1039","DOI":"10.1002\/art.1780290816","volume":"29","author":"R Altman","year":"1986","unstructured":"Altman R, Asch E, Bloch D, et al. Development of criteria for the classification and reporting of osteoarthritis. Classification of osteoarthritis of the knee. Diagnostic and Therapeutic Criteria Committee of the American Rheumatism Association. Arthritis Rheum. 1986;29:1039\u201349.","journal-title":"Arthritis Rheum"},{"key":"1960_CR24","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1016\/j.joca.2004.12.002","volume":"13","author":"M Deberg","year":"2005","unstructured":"Deberg M, Labasse A, Christgau S, et al. New serum biochemical markers (Coll 2-1 and Coll 2-1 NO2) for studying oxidative-related type II collagen network degradation in patients with osteoarthritis and rheumatoid arthritis. Osteoarthritis Cartilage. 2005;13:258\u201365.","journal-title":"Osteoarthritis Cartilage"},{"key":"1960_CR25","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1136\/ard.2007.073452","volume":"67","author":"M Deberg","year":"2008","unstructured":"Deberg M, Dubuc JE, Labasse A, et al. One-year follow-up of Coll2-1, Coll2-1NO2 and myeloperoxydase serum levels in osteoarthritis patients after hip or knee replacement. Ann Rheum Dis. 2008;67:168\u201374.","journal-title":"Ann Rheum Dis"},{"key":"1960_CR26","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1186\/1472-6882-14-159","volume":"14","author":"Y Henrotin","year":"2014","unstructured":"Henrotin Y, Gharbi M, Dierckxsens Y, et al. Decrease of a specific biomarker of collagen degradation in osteoarthritis, Coll2-1, by treatment with highly bioavailable curcumin during an exploratory clinical trial. BMC Complement Altern Med. 2014;14:159\u201365.","journal-title":"BMC Complement Altern Med"},{"key":"1960_CR27","doi-asserted-by":"publisher","first-page":"77","DOI":"10.2174\/1874312901408010077","volume":"8","author":"T Appelboom","year":"2014","unstructured":"Appelboom T, Maes N, Albert A. A new Curcuma extract (Flexofytol\u00ae) in osteoarthritis: results from a Belgian real-life experience. Open Rheumatol J. 2014;8:77\u201381.","journal-title":"Open Rheumatol J"},{"key":"1960_CR28","doi-asserted-by":"publisher","first-page":"167","DOI":"10.4236\/ojra.2017.74017","volume":"7","author":"S De Breucker","year":"2017","unstructured":"De Breucker S, Rouvi\u00e8re H, M\u00e9lot C, Appelboom T. Flexofytol\u00ae (a Belgian curcumin extract) for the treatment of aged patients with osteoarthritis and comorbidity. Open J Rheumatol Autoimmune Dis. 2017;7:167\u201377.","journal-title":"Open J Rheumatol Autoimmune Dis"},{"issue":"5","key":"1960_CR29","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1097\/00006324-200205000-00011","volume":"79","author":"R du Toit","year":"2002","unstructured":"du Toit R, Pritchard N, Heffernan S, Simpson T, Fonn D. A comparison of three different scales for rating contact lens handling. Optom Vis Sci. 2002;79(5):313\u201320.","journal-title":"Optom Vis Sci"},{"key":"1960_CR30","doi-asserted-by":"publisher","first-page":"1800","DOI":"10.1111\/1750-3841.13348","volume":"81","author":"Y Wang","year":"2016","unstructured":"Wang Y, Wang L, Zhu X, Wang D, Li X. Choleretic activity of turmeric and its active ingredients. J Food Sci. 2016;81:1800\u20136.","journal-title":"J Food Sci"}],"container-title":["Arthritis Research &amp; Therapy"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13075-019-1960-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s13075-019-1960-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13075-019-1960-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,7,25]],"date-time":"2020-07-25T23:11:30Z","timestamp":1595718690000},"score":1,"resource":{"primary":{"URL":"https:\/\/arthritis-research.biomedcentral.com\/articles\/10.1186\/s13075-019-1960-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,7,27]]},"references-count":30,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2019,12]]}},"alternative-id":["1960"],"URL":"https:\/\/doi.org\/10.1186\/s13075-019-1960-5","relation":{},"ISSN":["1478-6362"],"issn-type":[{"value":"1478-6362","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,7,27]]},"assertion":[{"value":"15 November 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 July 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 July 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The study protocol was approved by the Central Ethics Committee of the University Hospital of Li\u00e8ge in Belgium (namely Comit\u00e9 d\u2019Ethique Hospitalo-Facultaire Universitaire de Li\u00e8ge), agreement number: 707. This RCT was also registered on Clinical  on 13 September 2016 (NCT02909621).","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"YH is a consultant for Tilman SA and the founder and chairman of Artialis SA, a spin-off company of the University of Li\u00e8ge developing biomarkers. Artialis SA is the manufacturer of coll2-1 immunoassay. YD is an employee of Tilman SA. All other authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"179"}}