<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.4 20241031//EN"
        "https://jats.nlm.nih.gov/publishing/1.4/JATS-journalpublishing1-4.dtd">
<article  article-type="other"        dtd-version="1.4">
            <front>

                <journal-meta>
                                                                <journal-id>etd</journal-id>
            <journal-title-group>
                                                                                    <journal-title>Ege Tıp Dergisi</journal-title>
            </journal-title-group>
                            <issn pub-type="ppub">1016-9113</issn>
                                        <issn pub-type="epub">2147-6500</issn>
                                                                                            <publisher>
                    <publisher-name>Ege Üniversitesi</publisher-name>
                </publisher>
                    </journal-meta>
                <article-meta>
                                        <article-id pub-id-type="doi">10.19161/etd.648590</article-id>
                                                                                                                                                                                            <title-group>
                                                                                                                        <trans-title-group xml:lang="en">
                                    <trans-title>New therapy methods in osteoarthritis</trans-title>
                                </trans-title-group>
                                                                                                                                                                                                <article-title>Osteoartrozda yeni tedavi yöntemleri</article-title>
                                                                                                    </title-group>
            
                                                    <contrib-group content-type="authors">
                                                                        <contrib contrib-type="author">
                                                                    <contrib-id contrib-id-type="orcid">
                                        https://orcid.org/0000-0001-5325-4424</contrib-id>
                                                                <name>
                                    <surname>Özer</surname>
                                    <given-names>Diren</given-names>
                                </name>
                                                                    <aff>Ege Üniversitesi Tıp Fakültesi, Fiziksel Tıp ve Rehabilitasyon Anabilim Dalı</aff>
                                                            </contrib>
                                                    <contrib contrib-type="author">
                                                                    <contrib-id contrib-id-type="orcid">
                                        https://orcid.org/0000-0002-9781-2712</contrib-id>
                                                                <name>
                                    <surname>Eyigör</surname>
                                    <given-names>Sibel</given-names>
                                </name>
                                                                    <aff>Ege Üniversitesi Tıp Fakültesi, Fiziksel Tıp ve Rehabilitasyon Anabilim Dalı</aff>
                                                            </contrib>
                                                                                </contrib-group>
                        
                                        <pub-date pub-type="pub" iso-8601-date="20191025">
                    <day>10</day>
                    <month>25</month>
                    <year>2019</year>
                </pub-date>
                                                                <fpage>14</fpage>
                                        <lpage>21</lpage>
                        
                        <history>
                                    <date date-type="received" iso-8601-date="20181019">
                        <day>10</day>
                        <month>19</month>
                        <year>2018</year>
                    </date>
                                                    <date date-type="accepted" iso-8601-date="20190815">
                        <day>08</day>
                        <month>15</month>
                        <year>2019</year>
                    </date>
                            </history>
                                        <permissions>
                    <copyright-statement>Copyright © 1962, Ege Tıp Dergisi</copyright-statement>
                    <copyright-year>1962</copyright-year>
                    <copyright-holder>Ege Tıp Dergisi</copyright-holder>
                </permissions>
            
                                                                                                <trans-abstract xml:lang="en">
                            <p>Osteoarthritis (OA) is the most common form of arthritis. Despite the many challenges presented by clinical trials in OA, improvements in our understanding of disease pathogenesis and a move to treat pain, as well as underlying disease process, mean there are now many new pharmacological therapies currently in various stages of clinical trials. Some challenges remain, but opportunities for improving symptoms and disease process in OA in the clinic with new pharmacological agents would appear to be on the close horizon</p></trans-abstract>
                                                                                                                                    <abstract><p>Osteoartroz (OA) en yaygın artrit şeklidir. OA&#039;da klinik çalışmaların sunduğu birçok zorluğa rağmen, hastalık patogenezi, hastalık süreci ve ağrının tedavisinin yanı sıra altta yatan hastalığın tedavisinde birçok yeni farmakolojik tedaviler ve klinik araştırmalar vardır. Yeni farmakolojik ajanlar ile klinikte OA&#039;da semptomların ve hastalık sürecinin iyileştirilmesine yönelik fırsatlar ufukta görünmektedir.</p></abstract>
                                                            
            
                                                                                        <kwd-group>
                                                    <kwd>Osteoartroz (OA)</kwd>
                                                    <kwd>  ilaç</kwd>
                                                    <kwd>  klinik çalışma</kwd>
                                                    <kwd>  tedavi</kwd>
                                            </kwd-group>
                            
                                                <kwd-group xml:lang="en">
                                                    <kwd>Osteoarthritis (OA)</kwd>
                                                    <kwd>  drug</kwd>
                                                    <kwd>  clinical trial</kwd>
                                                    <kwd>  reatment</kwd>
                                            </kwd-group>
                                                                                                                                        </article-meta>
    </front>
    <back>
                            <ref-list>
                                    <ref id="ref1">
                        <label>1</label>
                        <mixed-citation publication-type="journal">Watt FE, Gulati M. New Drug Treatments for Osteoarthritis: What is on the horizon? EMJ 2017;2: 50-8.</mixed-citation>
                    </ref>
                                    <ref id="ref2">
                        <label>2</label>
                        <mixed-citation publication-type="journal">Ondresik M, Maia FRA, Morais AS, et al. Management of knee osteoarthritis. Current status and future trends. Biotechnol Bioeng 2017;114:717-39.</mixed-citation>
                    </ref>
                                    <ref id="ref3">
                        <label>3</label>
                        <mixed-citation publication-type="journal">Cucchiarini M, Henrionnet C, Mainard D, et al. New trends in articular cartilage repair. J Exp Orthop 2015; 2:8. DOI 10.1186/s40634-015-0026-0</mixed-citation>
                    </ref>
                                    <ref id="ref4">
                        <label>4</label>
                        <mixed-citation publication-type="journal">Mobasheri A. The Future of Osteoarthritis Therapeutics: Targeted Pharmacological Therapy. Curr Rheumatol Rep 2013;15:364. doi: 10.1007/s11926-013-0385-4.</mixed-citation>
                    </ref>
                                    <ref id="ref5">
                        <label>5</label>
                        <mixed-citation publication-type="journal">Smith SR, Deshpande BR, Collins JE, Katz JN, Losina E. Comparative pain reduction of oral non-steroidal anti-inflammatory drugs and opioids for knee osteoarthritis: systematic analytic review. Osteoarthritis Cartilage 2016;24(6):962-72.</mixed-citation>
                    </ref>
                                    <ref id="ref6">
                        <label>6</label>
                        <mixed-citation publication-type="journal">Bingham CO, Buckland-Wright JC, Garnero P, et al. Risedronate decreases biochemical markers of cartilage degradation but does not decrease symptoms or slow radiographic progression in patients with medial compartment osteoarthritis of the knee: results of the two-year multinational knee osteoarthritis structural arthritis study. Arthritis Rheum 2006;54(11):3494-507.</mixed-citation>
                    </ref>
                                    <ref id="ref7">
                        <label>7</label>
                        <mixed-citation publication-type="journal">Rossini M, Adami S, Fracassi E, et al. Effects of intra- articular clodronate in the treatment of knee osteoarthritis: results of a double- blind, randomized placebo-controlled trial. Rheumatol Int 2015;35(2):255-63.</mixed-citation>
                    </ref>
                                    <ref id="ref8">
                        <label>8</label>
                        <mixed-citation publication-type="journal">Laslett LL, Kingsbury SR, Hensor EM, Bowes MA, Conaghan PG. Effect of bisphosphonate use in patients with symptomatic and radiographic knee osteoarthritis: data from the Osteoarthritis Initiative. Ann Rheum Dis 2014;73(5):824-30.</mixed-citation>
                    </ref>
                                    <ref id="ref9">
                        <label>9</label>
                        <mixed-citation publication-type="journal">Walzer SM, Weinmann D, Toegel S. Medical Plant Extracts for Treating Knee Osteoarthritis: a Snapshot of Recent Clinical Trials and Their Biological Background. Curr Rheumatol Rep 2015;17(18):54. doi: 10.1007/s11926-015-0530-3.</mixed-citation>
                    </ref>
                                    <ref id="ref10">
                        <label>10</label>
                        <mixed-citation publication-type="journal">Pelletier JP, Roubille C, Raynauld JP, et al. Disease-modifying effect of strontium ranelate in a subset of patients from the Phase III knee osteoarthritis study SEKOIA using quantitative MRI: reduction in bone marrow lesions protects against cartilage loss. Ann Rheum Dis 2015;74(2):422-9.</mixed-citation>
                    </ref>
                                    <ref id="ref11">
                        <label>11</label>
                        <mixed-citation publication-type="journal">Roubille C, Pelletier JM, Raynauldet JP, et al. Meniscal extrusion promotes knee osteoarthritis structural progression: protective effect of strontium ranelate treatment in a phase III clinical trial. Arthritis Res Ther 2015;17:82. doi: 10.1186/s13075-015-0579-4</mixed-citation>
                    </ref>
                                    <ref id="ref12">
                        <label>12</label>
                        <mixed-citation publication-type="journal">Bijlsma JW, Berenbaum F, Lafeber FP. Osteoarthritis: an update with relevance for clinical practice. Lancet 2011;377(9783):2115-26.</mixed-citation>
                    </ref>
                                    <ref id="ref13">
                        <label>13</label>
                        <mixed-citation publication-type="journal">Lark MW, Bayne EK, Flanagan J, et al. Aggrecan degradation in human cartilage. Evidence for both matrix metalloproteinase and aggrecanase activity in normal, osteoarthritic, and rheumatoid joints. J Clin Invest 1997;100(1):93-106.</mixed-citation>
                    </ref>
                                    <ref id="ref14">
                        <label>14</label>
                        <mixed-citation publication-type="journal">Nagase H, Kashiwagi M. Aggrecanases and cartilage matrix degradation. Arthritis Res Ther 2003;5(2):94-103.</mixed-citation>
                    </ref>
                                    <ref id="ref15">
                        <label>15</label>
                        <mixed-citation publication-type="journal">Stanton H, Rogerson FM, East CJ, et al. ADAMTS5 is the major aggrecanase in mouse cartilage in vivo and in vitro. Nature 2005;434(7033):648-52.</mixed-citation>
                    </ref>
                                    <ref id="ref16">
                        <label>16</label>
                        <mixed-citation publication-type="journal">Swearingen CJ, Majumdar S, Simsek I, et al. Radiographic Outcomes from a Randomized, Double-Blind, Placebo-Controlled, Phase 1 Study of a Novel, Intra-Articular, Injectable, Wnt Inhibitor (SM04690) in the Treatment of Osteoarthritis of the Knee. Abstract 2350. ACR/ARHP Annual Meeting, 2016. Washington, DC.</mixed-citation>
                    </ref>
                                    <ref id="ref17">
                        <label>17</label>
                        <mixed-citation publication-type="journal">Cook SD. Preclinical and clinical evaluation of osteogenic protein-1 (BMP-7) in bony sites. Orthopedics 1999;22:669–671.</mixed-citation>
                    </ref>
                                    <ref id="ref18">
                        <label>18</label>
                        <mixed-citation publication-type="journal">Fidelix TS, Soares BG, Trevisani VF. Diacerein for osteoarthritis. Cochrane Database Syst Rev 2006;1, CD005117.</mixed-citation>
                    </ref>
                                    <ref id="ref19">
                        <label>19</label>
                        <mixed-citation publication-type="journal">Fransen M, Agaliotis M, Nairn L, et al. Glucosamine and chondroitin for knee osteoarthritis: a double-blind randomised placebo-controlled clinical trial evaluating single and combination regimens. Ann Rheum Dis 2015 May;74(5):851-8.</mixed-citation>
                    </ref>
                                    <ref id="ref20">
                        <label>20</label>
                        <mixed-citation publication-type="journal">Ciullini Mannurita S, Vignoli M, Bianchi L, et al. CACP syndrome: identification of five novel mutations and of the first case of UPD in the largest European cohort. Eur J Hum Genet 2014;22(2):197–201.</mixed-citation>
                    </ref>
                                    <ref id="ref21">
                        <label>21</label>
                        <mixed-citation publication-type="journal">He WW, Kuang MJ, Zhao J, Sun L, Lu B, Wang Y. Efficacy and safety of intraarticular hyaluronic acid and corticosteroid for knee osteoarthritis: A meta-analysis. Int J Surg 2017 Jan 27;39:95</mixed-citation>
                    </ref>
                                    <ref id="ref22">
                        <label>22</label>
                        <mixed-citation publication-type="journal">Cardiel M, Tak P, Bensen W, et al. A phase 2 randomized, double-blind study of AMG 108, a fully human monoclonal antibody to IL-1R, in patients with rheumatoid arthritis. Arthritis Res Ther 2010; 12(5): R192.</mixed-citation>
                    </ref>
                                    <ref id="ref23">
                        <label>23</label>
                        <mixed-citation publication-type="journal">Gilbert A, Bikker A, Neil S. Advances in the development of novel aggrecanase inhibitors, Expert Opin Ther Pat 2011; 21:1-12.</mixed-citation>
                    </ref>
                                    <ref id="ref24">
                        <label>24</label>
                        <mixed-citation publication-type="journal">Burleigh A, Chanalaris A, Gardiner MD, et al. Joint immobilization prevents murine osteoarthritis and reveals the highly mechanosensitive nature of protease expression in vivo. Arthritis Rheum 2012;64(7):2278-88.</mixed-citation>
                    </ref>
                                    <ref id="ref25">
                        <label>25</label>
                        <mixed-citation publication-type="journal">Walsh DA, Mapp PI, Kelly S. Calcitonin gene-related peptide in the joint: contributions to pain and inflammation. Br J Clin Pharmacol 2015;80(5):965-78.</mixed-citation>
                    </ref>
                                    <ref id="ref26">
                        <label>26</label>
                        <mixed-citation publication-type="journal">Chong KW, Chanalaris A, Burleigh A, et al. Fibroblast growth factor 2 drives changes in gene expression following injury to murine cartilage in vitro and in vivo. Arthritis Rheum 2013; 65(9):2346-55.</mixed-citation>
                    </ref>
                                    <ref id="ref27">
                        <label>27</label>
                        <mixed-citation publication-type="journal">Chevalier X, Ravaud P, Maheu E, et al. Adalimumab in patients with hand osteoarthritis refractory to analgesics and NSAIDs: a randomised, multicentre, double-blind, placebo-controlled trial. Ann Rheum Dis 2015;74(9):1697-705.</mixed-citation>
                    </ref>
                                    <ref id="ref28">
                        <label>28</label>
                        <mixed-citation publication-type="journal">Hellio le Graverand MP, Clemmer RS, Redifer P, et al. A 2-year randomised, double-blind, placebo- controlled, multicentre study of oral selective iNOS inhibitor, cindunistat (SD-6010), in patients with symptomatic osteoarthritis of the knee. Ann Rheum Dis 2013;72(2):187-95.</mixed-citation>
                    </ref>
                                    <ref id="ref29">
                        <label>29</label>
                        <mixed-citation publication-type="journal">Neogi T. The epidemiology and impact of pain in osteoarthritis. Osteoarthritis Cartilage 2013;21(9):1145-53.</mixed-citation>
                    </ref>
                                    <ref id="ref30">
                        <label>30</label>
                        <mixed-citation publication-type="journal">Watt FE, Ismail HM, Didangelos A, et al. Src and fibroblast growth factor 2 independently regulate signaling and gene expression induced by experimental injury to intact articular cartilage. Arthritis Rheum 2013;65(2): 397-407.</mixed-citation>
                    </ref>
                                    <ref id="ref31">
                        <label>31</label>
                        <mixed-citation publication-type="journal">Goldring MB. The role of cytokines as inflammatory mediators in osteoarthritis: lessons from animal models. Connective Tissue Res 1999;40(1):1-11.</mixed-citation>
                    </ref>
                                    <ref id="ref32">
                        <label>32</label>
                        <mixed-citation publication-type="journal">Sacitharan P, Lwin S, Gharios GB, Edwards JR. Spermidine restores dysregulated autophagy and polyamine synthesis in aged and osteoarthritic chondrocytes via EP300 Exp Mol Med 2018;50(9): 123. doi: 10.1038/s12276-018-0149-3.</mixed-citation>
                    </ref>
                                    <ref id="ref33">
                        <label>33</label>
                        <mixed-citation publication-type="journal">Long L, Soeken K, Ernst E. Herbal medicines for the treatment ofosteoarthritis: a systematic review. Rheumatology (Oxford) 2001;40(7):779–93.</mixed-citation>
                    </ref>
                                    <ref id="ref34">
                        <label>34</label>
                        <mixed-citation publication-type="journal">Whitehouse MW, Butters DE. Combination anti-inflammatory therapy: synergism in rats of NSAIDs/corticosteroids with some herbal/animal products. Inflammopharmacology 2003;11(4):453</mixed-citation>
                    </ref>
                                    <ref id="ref35">
                        <label>35</label>
                        <mixed-citation publication-type="journal">Di Y, Han C, Zhao L, Ren Y. Is local platelet-rich plasma injection clinically superior to hyaluronic acid for treatment of knee osteoarthritis? A systematic review of randomized controlled trials.Arthritis Res Ther 2018;20(1):128.</mixed-citation>
                    </ref>
                                    <ref id="ref36">
                        <label>36</label>
                        <mixed-citation publication-type="journal">Rabago D, Zgierska A, Fortney L, et al. Hypertonic Dextrose Injections (Prolotherapy) for Knee Osteoarthritis: Results of a Single-Arm Uncontrolled Study with 1-Year Follow-Up. Altern Complement Med 2012 Apr;18(4):408-14.</mixed-citation>
                    </ref>
                                    <ref id="ref37">
                        <label>37</label>
                        <mixed-citation publication-type="journal">Sampson S, Bemden A, Aufiero D. Stem cell therapies for treatment of cartilage and bone disorders: osteoarthritis, avascular necrosis, and non-union fractures. PM R 2015;7(4 Suppl):S26-S32.</mixed-citation>
                    </ref>
                                    <ref id="ref38">
                        <label>38</label>
                        <mixed-citation publication-type="journal">Fernandez-Cuadros ME, Perez-Moro OS, Mirón-Canelo JA. Could Ozone Be Used as a Feasible Future Treatment in Osteoarthritis of the Knee? Divers Equal Health Care 2016;13(3): 232-239.</mixed-citation>
                    </ref>
                                    <ref id="ref39">
                        <label>39</label>
                        <mixed-citation publication-type="journal">Vannabouathong C, Bhandari M, Bedi A, et al. Nonoperative Treatments for Knee Osteoarthritis: An Evaluation of Treatment Characteristics and the Intra-Articular Placebo Effect: A Systematic Review. JBJS Rev 2018;6(7):e5 . doi: 10.2106/JBJS.RVW.17.00167.</mixed-citation>
                    </ref>
                                    <ref id="ref40">
                        <label>40</label>
                        <mixed-citation publication-type="journal">Kraus VB, Blanco FJ, Englund M, et al. OARSI Clinical Trials Recommendations: Soluble biomarker assessments in clinical trials in osteoarthritis. Osteoarthritis Cartilage 2015;23(5):686-97.</mixed-citation>
                    </ref>
                                    <ref id="ref41">
                        <label>41</label>
                        <mixed-citation publication-type="journal">Kluzek S, Sanchez-Santos MT, Leyland KM, et al. Painful knee but not hand osteoarthritis is an independent predictor of mortality over 23 years follow-up of a population-based cohort of middle-aged women. Ann Rheum Dis 2015;75(10):1749-56.</mixed-citation>
                    </ref>
                            </ref-list>
                    </back>
    </article>
