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1 ISSN São Paulo Medical Journal/Evidence for Health Care, 205 January ; 33():-68 S Ã O P A U L O E V I D E N C E F O R H E A L T H C A R E January - Volume 33 - Number Randomized clinical trial: Lateral wedge insole for knee osteoarthritis Prospective cohort study: Follow-up of women with inadequate Pap smears Retrospective study: Rates and reasons for blood donor deferral, Shiraz, Iran Prevalence study: Frequency of Epstein-Barr virus DNA sequences in human gliomas Medline, Lilacs, SciELO, Science Citation Index Expanded, Journal Citation Reports/ Sciences Edition (impact factor 0.703) and EBSCO Publishing Memorial da América Latina Federada da São Paulo Medical Journal does not charge authors for publication.

2 Unidade Itaim Unidade Anália Franco Rede D Or São Luiz. Preparado para o seu paciente. Pronto para você. A humanização e a tecnologia avançada fazem das Unidades do Hospital São Luiz referências em atendimento e infraestrutura, e o lugar ideal para você oferecer o melhor atendimento aos seus pacientes. Unidade Morumbi Unidade Jabaquara Itaim: () Anália Franco: () Morumbi: () Jabaquara: () Diretor técnico responsável Dr. José Jair James de Arruda Pinto CRM 47763

3 INDEX Correspondence to: ASSOCIAÇÃO PAULISTA DE MEDICINA Publicações Científicas Av. Brig. Luís Antônio, o andar São Paulo (SP) Brasil CEP Tel. (+55 ) ou (+55 ) Fax: (+55 ) serial&pid=56-380&ing=en&nrm=iso Editorial Why has the rise in obesity not reversed the decline in cardiovascular mortality? Cardiometabolic death rate trends in Brazil (980-20) Paulo Andrade Lotufo Original article 4 Experimental osteoarthritis model by means of medial meniscectomy in rats and effects of diacerein administration and hyaluronic acid injection Marcia Uchôa Rezende, Arnaldo José Hernandez, Claudia Regina Gomes Cardim Mendes Oliveira, Raul Bolliger Neto 3 Lateral wedge insole for knee osteoarthritis: randomized clinical trial Gustavo Constantino de Campos, Marcia Uchôa Rezende, Thiago Pasqualin, Renato Frucchi, Raul Bolliger Neto 20 Follow-up of women with inadequate Pap smears: a prospective cohort study Fanny López-Alegría, Dino Roberto Soares De Lorenzi, Orlando Quezada Poblete 28 Analysis of heparanase isoforms and cathepsin B in the plasma of patients with gastrointestinal carcinomas: analytical cross-sectional study Carina Mucciolo Melo, Clarice Silvia Taemi Origassa, Thérèse Rachell Theodoro, Leandro Luongo Matos, Thaís Aguilar Miranda, Camila Melo Accardo, Rodrigo Ippolito Bouças, Eloah Rabello Suarez, Madalena Maria Nunes Silva Pares, Daniel Reis Waisberg, Giovanna Canato Toloi, Helena Bonciani Nader, Jaques Waisberg, Maria Aparecida Silva Pinhal 36 Rates and reasons for blood donor deferral, Shiraz, Iran. A retrospective study Leila Kasraian, Neda arestani 43 Pattern, clinical features and response to corticoids of glomerular diseases in a Brazilian population. An analytical cross-sectional study Anaiara Lucena Queiroz, Dulce Maria Sousa Barreto, Geraldo Bezerra da Silva Junior, José Edísio da Silva Tavares Neto, Francisco Israel Costa, Régia Maria do Socorro Vidal Patrocínio, Elizabeth De Francesco Daher, Paulo Roberto Carvalho de Almeida Short communication 5 Frequency of Epstein-Barr virus DNA sequences in human gliomas Renata Fragelli Fonseca, Siane Lopes Bittencourt Rosas, José Antônio Oliveira, Anselmo Teixeira, Gilda Alves, Maria da Glória Costa Carvalho Case reports 55 Malignant ventricular tachycardia in acromegaly: a case report Zhe An, Yu-quan He, Guo-hui Liu, Li-li Ge, Wen-qi Zhang 60 Central diabetes insipidus: alert for dehydration in very low birth weight infants during the neonatal period. A case report Maria Lúcia Silveira Ferlin, Débora Simone Sales, Fábia Pereira Martins Celini, Carlos Eduardo Martinelli Junior Letter to the editor 64 Magnetic resonance imaging characteristics of intramuscular lipomas Ivan Chernev, Nadege Petit-Clair Response to letter to editor: Débora Balabram, Carla Cristina de Sousa Resende Cabral, Omar de Paula Ricardo Filho, Cristóvão Pinheiro de Barros Cochrane highlights 67 Pharmacological interventions for sleepiness and sleep disturbances caused by shift work Juha Liira, Jos H. Verbeek, Giovanni Costa, Tim R. Driscoll, Mikael Sallinen, Leena K. Isotalo, Jani H. Ruotsalainen Comments: Antonio Javier Marcos Salan 68 Multifocal versus monofocal intraocular lenses after cataract extraction Daniel Calladine, Jennifer R. Evans, Sweata Shah, Martin Leyland Comments: Noé Luiz Mendes de Marchi I Instructions for authors (www.scielo.br/spmj) Sao Paulo Med J. 205; 33():i-ii i

4 ORGANIZATION Founded in 932, a bimonthly publication of the Associação Paulista de Medicina Editors: Paulo Andrade Lotufo and Álvaro Nagib Atallah. Editorial advisor: Rachel Riera. Editorial assistant: Marina de Britto. Scientific journalist and editor: Patrícia Logullo (MTB: ). Editorial auxiliary: Joyce de Fátima Silva Nakamura. Associate editors: Adriana Seber, Aécio Flávio Teixeira de Góis, Airton Tetelbom Stein, Alexander Wagner Silva de Souza, Antonio José Gonçalves, Aytan Miranda Sipahi, Cristina Muccioli, Delcio Matos, Domingo Marcolino Braile, Edina Mariko Koga da Silva, Fernando Antonio de Almeida, Flávio Faloppa, Heráclito Barbosa de Carvalho, José Antônio Rocha Gontijo, José Carlos Costa Baptista-Silva, José Maria Soares Júnior, José Roberto Lapa e Silva, Laércio Joel Franco, Maria do Patrocínio Tenório Nunes, Milton de Arruda Martins, Moacir Fernandes de Godoy, Olavo Pires de Camargo, Renato Corrêa Baena, Sergio Tufik, Vania dos Santos Nunes. Proofreading: David Elliff. Desktop publishing: Zeppelini Editorial (www.zeppelini.com.br). Listed in: Medline, Lilacs, SciELO, Science Citation Index Expanded and Journal Citation Reports/Sciences Edition (impact factor 0.588) and EBSCO publishing. International Board: Alexandre Wagner Silva de Souza (University Medical Center Groningen, Groningen, Netherlands), Charles J. Menkes (Cochin Hospital, Paris, France), José Fragata (Hospital Cuf Infant Santo, Lisbon), Luiz Dratcu (Guy s Hospital, London, and Maudsley NHS Trust, York Clinic, London), Marcelo Cypel (University Health Network, Toronto, Canada), Karla Soares-Weiser (Enhance Reviews Ltd, Wantage, United Kingdom), Tirone E. David (Toronto General Hospital, Toronto, Canada), Mário Viana de Queiroz (Hospital de Santa Maria, Lisbon), Wadih Arap (MD Anderson Cancer Center, University of Texas, Houston, United States), Wellington Cardoso (Boston University, Boston, United States). All articles published, including editorials and letters, represent the opinions of the authors and do not reflect the official policy of the Associação Paulista de Medicina or the institution with which the authors are affiliated, unless this is clearly specified. All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopy, recording, or any information storage and retrieval system, without permission in writing from the publisher. Copyright 205 by Associação Paulista de Medicina. SPMJ website: access to the entire São Paulo Medical Journal/Revista Paulista de Medicina website is free to all. We will give at least six months notice of any change in this policy. SPMJ printed version: six issues/year; volume/year, beginning on first Thursday in January. One-year subscription for the year 205: individual US$ 65; institutional US$ 230. Scientific Council Abrão Rapoport Hospital Heliópolis, São Paulo Adriana Costa e Forti Faculdade de Medicina, Universidade Federal do Ceará Alexandre Fogaça Cristante Faculdade de Medicina da Universidade de São Paulo Álvaro Nagib Atallah Escola Paulista de Medicina, Universidade Federal de São Paulo Auro del Giglio Faculdade de Medicina da Fundação ABC Carlos Alberto Morais Sá Universidade do Rio de Janeiro - UNIRIO Carmen Cabanelas Pazos de Moura Instituto Carlos Chagas Filho, Universidade Federal do Rio de Janeiro Cármino Antonio De Souza Faculdade de Ciências Médicas, Universidade Estadual de Campinas Dario Birolini Faculdade de Medicina, Universidade de São Paulo Eduardo Maia Freese de Carvalho Faculdade de Medicina, Universidade Federal de Pernambuco, Centro de Pesquisas Aggeu Magalhães - CpqAM/FIOCRUZ. Egberto Gaspar de Moura Instituto de Biologia Roberto Alcantara Gomes, Universidade Estadual do Rio de Janeiro Eliézer Silva Hospital Israelita Albert Einstein, São Paulo Emílio Antonio Francischetti - Faculdade de Medicina da Universidade Estadual do Rio de Janeiro Emmanuel de Almeida Burdmann Faculdade de Medicina de São José do Rio Preto Fabio Bessa Lima Instituto de Ciências Biomédicas, Universidade de São Paulo Florence Kerr-Corrêa Faculdade de Medicina de Botucatu, Universidade Estadual de São Paulo Francisco José Penna Faculdade de Medicina Universidade Federal de Minas Gerais Geraldo Rodrigues de Lima Escola Paulista de Medicina, Universidade Federal de São Paulo Irineu Tadeu Velasco Faculdade de Medicina da Universidade de São Paulo João Renato Rebello Pinho Instituto Adolfo Lutz, Secretaria de Estado da Saúde de São Paulo Joel Spadaro Faculdade de Ciências Médicas de Botucatu, Universidade Estadual de São Paulo Jorge Pinto Ribeiro Faculdade de Medicina, Universidade Federal do Rio Grande do Sul Jorge Sabbaga Hospital Alemão Oswaldo Cruz, São Paulo José Antonio Marin-Neto Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo José Carlos Nicolau Instituto do Coração, Universidade de São Paulo José Geraldo Mill Faculdade de Medicina, Universidade Federal do Espírito Santo José Mendes Aldrighi Faculdade de Saúde Pública, Universidade de São Paulo José Roberto Lapa e Silva Instituto de Doenças do Tórax, Universidade Federal do Rio de Janeiro Leopoldo Soares Piegas Instituto Dante Pazzanese de Cardiologia, São Paulo Luiz Jacintho da Silva Faculdade de Ciências Médicas, Universidade Estadual de Campinas Luiz Paulo Kowalski Hospital AC Camargo, São Paulo Márcio Abrahão Escola Paulista de Medicina, Universidade Federal de São Paulo Maria Inês Schmidt Faculdade de Medicina, Universidade Federal do Rio Grande do Sul Maurício Mota de Avelar Alchorne Escola Paulista de Medicina, Universidade Federal de São Paulo Mauro Schechter Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro Milton de Arruda Martins Faculdade de Medicina, Universidade de São Paulo Moysés Mincis Faculdade de Ciências Médicas de Santos Nelson Hamerschlak Hospital Israelita Albert Einstein, São Paulo Noedir Antônio Groppo Stolf Faculdade de Medicina, Universidade de São Paulo Pérsio Roxo Júnior Faculdade de Medicina de Ribeirão Preto Raul Cutait Hospital Sírio-Libanês, São Paulo Raul rão Fleury Instituto Lauro de Souza Lima, Coordenadoria dos Institutos de Pesquisa da Secretaria de Saúde de São Paulo Raul Marino Junior Faculdade de Medicina, Universidade de São Paulo Ricardo Brandt de Oliveira Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo Roberto A. Franken Faculdade de Ciências Médicas da Santa Casa de Misericórdia de São Paulo Ruy Laurenti Faculdade de Saúde Pública, Universidade de São Paulo Soubhi Kahhale Faculdade de Medicina, Universidade de São Paulo Wilson Roberto Catapani Faculdade de Medicina do ABC, Santo André Wilson Cossermelli Reclin Reumatologia Clínica, São Paulo Diretoria Executiva da Associação Paulista de Medicina (Triênio ) Presidente: Florisval Meinão º Vice-Presidente: Roberto Lotfi Júnior 2º Vice-Presidente: Donaldo Cerci da Cunha 3º Vice-Presidente: Paulo De Conti 4º Vice-Presidente: Akira Ishida Secretário Geral: Paulo Cezar Mariani º Secretário: Antonio José Gonçalves Diretor Administrativo: Lacildes Rovella Júnior Diretor Administrativo Adjunto: Roberto de Mello º Diretor de Patrimônio e Finanças: Carlos Alberto Martins Tosta 2º Diretor de Patrimônio e Finanças: Claudio Alberto Galvão Bueno Da Silva Diretor Cientí fico: Paulo Andrade Lotufo Diretor Cientí fico Adjunto: Álvaro Nagib Atallah Diretor de Defesa Profi ssional: João Sobreira de Moura Neto Diretor de Defesa Pro fissional Adjunto: Marun David Cury Diretor de Comunicações: Ivan Melo De Araújo Diretor de Comunicações Adjunto: Amilcar Martins Giron Diretor de Marketing: Ademar Anzai Diretor de Marketing Adjunto: Nicolau D Amico Filho Diretora de Eventos: Mara Edwirges Rocha Gândara Diretora de Eventos Adjunta: Regina Maria Volpato Bedone Diretor de Tecnologia de Informação: Antônio Carlos Endrigo Diretor de Tecnologia de Informação Adjunto: Marcelo Ferraz De Campos Diretor de Previdência e Mutualismo: Paulo Tadeu Falanghe Diretor de Previdência e Mutualismo Adjunto: Clóvis Francisco Constantino Diretor Social: Alfredo de Freitas Santos Filho Diretora Social Adjunto: Christina Hajaj Gonzalez Diretora de Responsabilidade Social: Evangelina de Araujo Vormittag Diretor de Responsabilidade Social Adjunto: José Eduardo Paciência Rodrigues Diretor Cultural: Guido Arturo Palomba Diretor Cultural Adjunto: José Luiz Gomes do Amaral Diretora de Serviços aos Associados: Vera Lúcia Nocchi Cardim Diretor de Serviços aos Associados Adjunto: João Carlos Sanches Anéas Diretor de Economia Médica: Tomás Patrício Smith-Howard Diretora de Economia Médica Adjunta: Marly Lopes Alonso Mazzucato º Diretor Distrital: Everaldo Porto Cunha 2º Diretora Distrital: Lourdes Teixeira Henriques 3º Diretor Distrital: Camillo Soubhia Júnior 4º Diretor Distrital: Wilson Olegário Campagnone 5º Diretor Distrital: Flavio Leite Aranha Junior 6º Diretora Distrital: Cleusa Cascaes Dias 7º Diretora Distrital: Irene Pinto Silva Masci 8º Diretor Distrital: Helencar Ignácio 9º Diretora Distrital: Margarete Assis Lemos 0º Diretor Distrital: Enio Luiz Tenório Perrone º Diretora Distrital: Zilda Maria Tosta Ribeiro 2º Diretor Distrital: Luís Eduardo Andreossi 3º Diretor Distrital: Marcio Aguilar Padovani 4º Diretor Distrital: Marcelo Torrente Silva ii Sao Paulo Med J. 205; 33():i-ii

5 DOI: 0.590/ EDITORIAL Why has the rise in obesity not reversed the decline in cardiovascular mortality? Cardiometabolic death rate trends in Brazil (980-20) Por que o aumento da obesidade não reverte o declínio da mortalidade por doença cardiovascular? Tendências de mortalidade por evento cardiometabólico no Brasil (980-20) Paulo Andrade Lotufo I Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, Brazil I MD, PhD. Titular Professor, Discipline of Internal Medicine, Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, Brazil. In the November 2000 issue of this journal, the editorial made a prediction that the decreasing trend of cardiovascular death rates in Brazil that had been seen in the 990s would flatten out, as the first effect of the increasing prevalence of obesity in this country. The premises for this statement were consistent: as the average body mass index increases, diabetes prevalence rates consequently rise and act directly on the incidence and case-fatality rates of cardiovascular diseases, thus causing the descending trend of cardiovascular deaths to flatten out and then possibly start an upward trend. Fourteen years after this editorial, I regret to inform all our readers that this prophecy (which I wrote) did not come to pass. The reality is that obesity is increasing in Brazil, 2 as it is everywhere, 3 and cardiovascular mortality rates are declining in Brazil, 4 as in most other countries. 5 To explain this apparent paradox, hypotheses such as the notion that the body mass index is not a good surrogate of adiposity as a risk for atherosclerosis and high blood pressure have been put forward. 6 Another reason may relate to the improvement of medical care, starting with greater control over risk factors at the primary care level, and especially the introduction of new protocols for cardiovascular emergency and a role for statins/aspirin/beta-blockers after myocardial infarction. 7 Another possibility is that this paradox may have been caused by a nosological artifact: a shift in the underlying cause of death from cardiovascular diseases to diabetes. The rationale for considering that there may be a classification bias is that, in most cases, people with diabetes die due to heart disease and stroke. However, this has been changing since 996, with the adoption of the 0 th revision of the International Classification of Diseases (ICD-0), in which both diabetes and a well-defined final cardiovascular event can be considered to be the underlying cause of death. This nosological artifact has been found not to be limited to Brazil and has also been shown in countries like Mexico and the United States. 8 This rationale has been used recently for comparisons of mortality data between countries. 9 To test this hypothesis, I analyzed the trends in assignment of the underlying cause of death over a period of three decades from 980 to 20, according to gender. This analysis concentrated on the age group from 30 to 69 years, because there are few cardiovascular deaths at younger ages (only 2.5% of cardiovascular deaths were among individuals under 30 years of age during this period), and because a high proportion of such deaths among individuals over the age of 70 years cannot be compared due to comorbidities. Since Brazil adopted ICD-0 only in 996, mortality data were classified according to the 9 th revision (ICD-9) from 980 to 995 and thereafter using ICD-0. I analyzed all cardiovascular diseases (chapters VII and IX of ICD-9 and ICD-0, respectively), coronary heart disease (CHD, codes: 40-5 and I-20-25) and stroke (code: and I-6-69), separately. Furthermore, I added the cases with diabetes (codes: 205 and E-0-5) to all the cardiovascular diseases, thus creating a category called cardiometabolic deaths. Sao Paulo Med J. 205; 33():-3

6 EDITORIAL Lotufo PA The investigation plan included: () review of the numbers in all the categories above, with calculation of the proportion of deaths relating to diagnoses that were listed as ill-defined causes of death; (2) adjustment of all crude death rates using the World Standard Population; (3) calculation of temporal changes to death rates using the Joinpoint 4.. software. 0 Figure displays the temporal trends of death rates due to cardiovascular diseases and diabetes for men and women in Brazil from 980 to 20. The average percentage change for men was different between the periods and , with a faster pace in the second period. For women, a decline in rates was observed from 980 to 992; the rates flattened out in ; and a new downward trend began in 996. Despite the improvement in coverage of the mortality information system and more reliable quality of death notification, which could have artificially inflated the rates, a persistent decline for cardiometabolic death rates can be seen in all periods. By examining a period with good quality of mortality data, such as 2005 to 20, it was possible to measure the average annual percentage change in cardiovascular diseases, CHD, stroke and diabetes (Table ). Significant declines in rates were estimated for all these diseases, except for diabetes in men. Comparison between the sexes showed that only for CHD was the reduction in rates faster for women. These temporal changes to death rates in Brazil show that the decline is occurring in the whole country, despite the shifting of nosological causes from cardiovascular diseases to diabetes. The faster decline of stroke death rates, compared with CHD, reveals that the phase of delayed cardiovascular epidemiological transition has ended. Moreover, the agenda for cardiovascular epidemiology needs to deeply consider the meaning of adiposity as a risk factor. Unfortunately, the early studies by Jean Vague in the 950s,,2 in which the components of obesity were evaluated separately, were endorsed by Table. Annual average percentage change (and 95% confidence interval) of age-adjusted death rates in Brazil over the period 2005 to 20 All cardiovascular diseases (ICD-0: chapter IX) Coronary heart disease (ICD-0: I-20-24) Cerebrovascular diseases (ICD-0: I-60-69) Diabetes (ICD-0: E0-5) Men -2.2 (-2.4 to -.82) -.33 (-.49 to -.6) (-3.57 to -2.96) 0.67 (-0.25 to.59) ICD-0 = International Classification of Diseases, 0 th revision. Women (-2.70 to -.99) (-3.90 to -.24) -3.4 (-3.50 to -2.78) -.92 (-2.45 to -.39) men women = (-. to -0.35) = -.7 (-.99 to -.43) = -.03 (-.54 to -0.52) = (-2.5 to -6.97) = -2.6 (-2.5 to -.80) *cardiometabolic diseases means all cardiovascular diseases (chapters VII and IX of ICD-9 and ICD-0, respectively) and diabetes (codes: 205 and E-0-5); the joinpoints and the annual percentage change were calculated using the Joinpoint software. Figure. Trends in cardiometabolic disease* death rates in Brazil from 980 to 20 with the annual percentage change of each joinpoint according to sex. 2 Sao Paulo Med J. 205; 33():-3

7 Why has the rise in obesity not reversed the decline in cardiovascular mortality? Cardiometabolic death rate trends in Brazil (980-20) EDITORIAL epidemiologists only in the early 980s. 3 Almost all articles on cardiometabolic trends contain classical final remarks such as further investigation are needed. Here, this statement is not a cliché. We need to understand the multiple components of this concept called obesity. Finally, I promise to limit my prophecies over the next three years of my term as editor-chief of this journal. 3. Lapidus L, Bengtsson C, Larsson B, et al. Distribution of adipose tissue and risk of cardiovascular disease and death: a 2 year follow up of participants in the population study of women in Gothenburg, Sweden. Br Med J (Clin Res Ed). 984;289(6454): Sources of funding: None Conflict of interest: None REFERENCES. Lotufo PA. Increasing obesity in Brazil: predicting a new peak of cardiovascular mortality. Sao Paulo Med J. 2000;8(6): Malta DC, Andrade SC, Claro RM, Bernal RT, Monteiro CA. Trends in prevalence of overweight and obesity in adults in 26 Brazilian state capitals and the Federal District from 2006 to 202. Rev Bras Epidemiol. 204;7 Suppl : Ng M, Fleming T, Robinson M, et al. Global, regional, and national prevalence of overweight and obesity in children and adults during : a systematic analysis for the Global Burden of Disease Study 203. Lancet. 204;384(9945): Lotufo PA, Goulart AC, Fernandes TG, Benseñor IM. A reappraisal of stroke mortality trends in Brazil ( ). Int J Stroke. 203;8(3): Moran AE, Forouzanfar MH, Roth GA, et al. Temporal trends in ischemic heart disease mortality in 2 world regions, 980 to 200: the Global Burden of Disease 200 study. Circulation. 204;29(4): van der Leeuw J, van der Graaf Y, Nathoe HM, et al. The separate and combined effects of adiposity and cardiometabolic dysfunction on the risk of recurrent cardiovascular events and mortality in patients with manifest vascular disease. Heart. 204;00(8): Rosamond WD, Chambless LE, Heiss G, et al. Twenty-two-year trends in incidence of myocardial infarction, coronary heart disease mortality, and case fatality in 4 US communities, Circulation. 202;25(5): Murray CJ, Dias RH, Kulkarni SC, et al. Improving the comparability of diabetes mortality statistics in the U.S. and Mexico. Diabetes Care. 2008;3(3): Di Cesare M, Bennett JE, Best N, et al. The contributions of risk factor trends to cardiometabolic mortality decline in 26 industrialized countries. Int J Epidemiol. 203;42(3): National Cancer Institute. Surveillance Research. Cancer Control and Population Sciences. Statistical Methodology and Applications Branch. Mission Statement. Available from: gov/branches/smab/. Accessed in 204 (Nov ).. Lotufo PA, Benseñor IM. Stroke mortality in Brazil: one example of delayed epidemiological cardiovascular transition. Int J Stroke. 2009;4(): Vague J. The degree of masculine differentiation of obesities: a factor determining predisposition to diabetes, atherosclerosis, gout, and uric calculous disease. Am J Clin Nutr. 956;4(): Date of first submission: October 28, 204 Last received: December 3, 204 Accepted: December 3, 204 Address for correspondence: Paulo Andrade Lotufo Centro de Pesquisa Clínica e Epidemiológica, Hospital Universitário, Universidade de São Paulo Av. Prof. Lineu Prestes, Butantã São Paulo (SP) Brasil Tel. (+55 ) Sao Paulo Med J. 205; 33():-3 3

8 ORIGINAL ARTICLE DOI: 0.590/ Experimental osteoarthritis model by means of medial meniscectomy in rats and effects of diacerein administration and hyaluronic acid injection Modelo experimental de osteoartrite através da meniscectomia medial em ratos e efeitos da administração de diacereína e da injeção de ácido hialurônico Marcia Uchôa Rezende I, Arnaldo José Hernandez II, Claudia Regina Gomes Cardim Mendes Oliveira I, Raul Bolliger Neto I Department of Orthopedics and Traumatology, Faculdade de Medicina, Universidade de São Paulo (FMUSP), São Paulo, Brazil I MD, PhD. Collaborating Professor, Department of Orthopedics and Traumatology, Faculdade de Medicina, Universidade de São Paulo (FMUSP), São Paulo, Brazil. II MD, PhD. Associate Professor, Department of Orthopedics and Traumatology, Faculdade de Medicina, Universidade de São Paulo (FMUSP), São Paulo, Brazil. KEY WORDS: Osteoarthritis. Knee. Anthraquinones. Hyaluronic acid. Models, animal. PALAVRAS-CHAVE: Osteoartrite. Joelho. Antraquinonas. Ácido hialurônico. Modelos animais. ABSTRACT CONTEXT AND OBJECTIVE: The development of a slow and progressive mechanical model for osteoarthritis is important for correlation with clinical practice, and for evaluating the effects of disease-modifying medications. A mechanical osteoarthritis model was developed to evaluate the effects of intra-articular hyaluronic acid (HA) injection and oral diacerein administration. DESIGN AND SETTING: Experimental study at the Department of Orthopedics and Traumatology, Universidade de São Paulo. METHOD: Total medial meniscectomy was performed on seven groups of ten Wistar rats each, comprising four control groups (C) and three study groups (S). C.I: operated, non-medicated; C.II: operated, injections of HA vehicle; C.III: non-operated, non-medicated; C.IV: operated, non-medicated, sacrificed three months post-meniscectomy; S.I: operated, receiving intra-articular HA injections; S.II: operated, oral diacerein from the third to the seventh postoperative month; S.III: operated, received both medications. All the animals (except C.IV) were sacrificed seven months post-meniscectomy. All femurs and tibias were assessed histologically. RESULTS: The most severe degenerative histological changes were in the tibias of the operated knees. On the contralateral side, all groups had mild changes on the tibial surface. The femoral surface had slight changes. C.I showed severe changes. S.II results matched those of C.IV. HA protected the tibial surface. S.II and S.III had similar results. CONCLUSIONS: ) The experimental model produced mild arthritis after three months and severe arthritis after seven months; 2) diacerein reduced the degenerative changes in both knees; 3) HA protected the joint cartilage; 4) Combining the two drugs did not improve the results. RESUMO CONTEXTO E OBJETIVO: Desenvolver um modelo osteoartrítico mecânico lento e progressivo é importante para correlação com a prática clínica e para avaliar os efeitos de medicamentos modificadores da doença. Um modelo mecânico de osteartrite foi desenvolvido para avaliar os efeitos de injeção intra-articular de hialuronato de sódio (AH) e de administração de diacereína oral. DESENHO E LOCAL: Estudo experimental no Departamento de Ortopedia e Traumatologia, Universidade de São Paulo. MÉTODO: Meniscectomia medial total foi feita em sete grupos de dez ratos Wistar, sendo quatro grupos controle (C) e três grupos estudo (E). C.I: operado, não medicado; C.II: operado, recebendo injeções do veículo do AH; C.III: não operado, não medicado; C.IV: operado, não medicado, sacrificado três meses pósmeniscectomia; EI: operado, recebendo injeções de AH intra-articular; E.II: operado, recebendo diacereína oral do terceiro ao sétimo mês pós-operatório; E.III: operado, recebeu ambas medicações. Todos os animais (exceto C.IV) foram sacrificados sete meses pós-meniscectomia. Todos os fêmures e tíbias foram analisados histologicamente. RESULTADOS: As alterações histológicas degenerativas mais graves encontram-se nas tíbias dos joelhos operados. No lado contra-lateral, todos os grupos apresentaram alterações leves na superfície tibial. A superfície femoral teve ligeiras alterações. C.I apresentou alterações graves. S.II equiparou seus resultados aos do grupo C.IV. AH protegeu a superfície tibial. S.II e S.III apresentaram resultados semelhantes. CONCLUSÕES: ) O modelo experimental gerou artrite leve aos três e grave aos sete meses; 2) Diacereína reduziu as alterações degenerativas de ambos os joelhos; 3) AH protege a cartilagem articular; 4) A associação dos dois fármacos não melhora os resultados. 4 Sao Paulo Med J. 205; 33():4-2

9 Experimental osteoarthritis model by means of medial meniscectomy in rats and effects of diacerein administration and hyaluronic acid injection ORIGINAL ARTICLE INTRODUCTION Osteoarthritis (OA) is classified as primary, idiopathic or secondary. Primary OA is either localized or generalized, based on whether less than three or three or more joints are affected, respectively. Idiopathic knee OA can be also divided according to the affected site into medial, lateral and/or patellofemoral compartment OA. Secondary OA is clearly a consequence of an earlier injury to the joint. 2 The fact that the pathological changes observed are similar in the two basic types of OA suggests that the final biochemical pathways that result in cartilage degeneration may also be similar. If so, pharmacological intervention directed toward basic biochemical malfunctions may be possible in all forms of OA. 2 Analgesics and non-steroidal anti-inflammatory drugs (NSAIDs) are used in accordance with the guidelines for treatment of osteoarthritis; 3 however, these medications do not prevent degenerative changes. NSAIDs have been correlated with serious adverse effects, and particularly renal and gastrointestinal effects. Selective cyclooxygenase-2 (COX-2) inhibitors reduce the incidence of upper gastrointestinal tract ulcerations; however, their side effects include fluid retention, hypertension, congestive heart failure, renal insufficiency and a risk of cardiovascular thrombosis. 4 On the other hand, it is claimed that drugs known as slowacting disease-modifying drugs relieve pain and slow down the progression of osteoarthritis. 4 Among these are intermittent intra-articular injection of hyaluronic acid and continuous oral intake of diacerein. Evidence of reduced degenerative changes has been shown with both of these medications. 4-6 Although experimental models for osteoarthritis may have their limitations and criticisms, OA-like pathological changes have been described in the knee joints of several species of animals. 2 These models have mainly consisted of mice, rabbits, dogs and sheep. 2,7- Sectioning of the anterior cruciate ligament 9,0 and partial or total meniscectomy in dogs, 2 rabbits 2,3-5 and sheep 5, have frequently been used as models for osteoarthritis. Less frequently used, but more aggressive models for osteoarthritis have been produced through combining ligament injury with meniscectomy in rabbits. 2,4,5 In view of the possibility that drug therapy may delay the development of this condition, we proposed an experimental model for osteoarthritis consisting of medial meniscectomy in rats, in order to register the degenerative changes and investigate the effects of so-called slow-acting disease-modifying drugs. Specifically in this study, we evaluated the two drugs mentioned above (oral diacerein and intra-articular hyaluronic acid) for reducing the development of osteoarthritis. The drugs were administered in the early stages of the disease either individually or in combination. OBJECTIVE The primary objective was to develop an experimental model for osteoarthritis in rats, by means of medial meniscectomy. The secondary objective was to investigate the effects of two drugs, diacerein (orally) and hyaluronic acid (intra-articular), separately and in association, when administered in the early stages of the disease caused by the experimental model for OA. METHODS This study was approved by the local Ethics Committee (CAPPesq), under the number 690/98. The study was conducted at LIM-4, IOT-HC-USP. Seventy adult male Wistar rats (age range from 8 to 6 weeks and weight range from 80 to 360 grams) were randomly assigned to four control groups (C) and three study groups (S): C.I - Ten rats were subjected to total medial meniscectomy of the right knee and were sacrificed 28 weeks (seven months) post-surgery. C.II - Ten rats were subjected to total medial meniscectomy of the right knee and were injected with the hyaluronic acid vehicle; they were sacrificed 28 weeks (seven months) post-surgery. C.III - Ten rats were not subjected to any procedure, and were sacrificed 28 weeks (seven months) after inclusion. C.IV - Ten rats were subjected to total medial meniscectomy of the right knee and were sacrificed twelve weeks (three months) post-surgery. S.I - Ten rats were subjected to total medial meniscectomy of the right knee and were injected with hyaluronic acid; they were sacrificed 28 weeks (seven months) post-surgery. S.II Ten rats were subjected to medial meniscectomy of the right knee and received oral diacerein; they were sacrificed 28 weeks (seven months) post-surgery. S.III Ten rats were subjected to medial meniscectomy of the right knee and received both oral diacerein and injected hyaluronic acid; they were sacrificed 28 weeks (seven months) post-surgery. All the rats with the exception of those in group C.III, which were not subjected to any operation, received intra-peritoneal anesthesia and the following procedures were performed. A 3-cm longitudinal incision was made on the medial aspect of the right knee. By retracting the quadriceps muscle anteriorly, the tibial collateral ligament was exposed and sectioned 3 mm from the joint line, and was then retracted. The medial meniscus was extracted (Figure ). The tibial collateral ligament was sutured with nylon 5-0. The quadriceps and skin were sutured with nylon 4-0. The wound was cleansed using saline and chlorhexidine gluconate solution. After the animals had recovered from the anesthesia, they received 2.5 mg of oral dipyrone. After surgery, the animals were kept in standard cages (three animals/cage). Sao Paulo Med J. 205; 33():4-2 5

10 ORIGINAL ARTICLE Rezende MU, Hernandez AJ, Oliveira CRGCM, Bolliger Neto R Four times a week, the animals were stimulated to walk up and down boxes for two hours during the night period. All the rats were weighed weekly, in order to adjust the oral medication dosage. The animals in groups S.I and S.III received intra-articular injections of hyaluronic acid in the right knee once a week for five weeks starting at the end of the 2 th postoperative week (third month), and two more injections in the 25 th and 26 th postoperative weeks. The animals in group C.II received only the hyaluronic acid vehicle, but in accordance with the same schedule as those in groups S.I and S.III. In order to receive the intra-articular injections, the animals were put into an anesthetic chamber that was supplied with 3% halothane and oxygen at a flow rate of 3 l/min. After becoming sedated, the animals were retrieved from the chamber and were prepared by means of shaving and antisepsis. The animals in groups S.I and S.III were injected with 0.04 ml of hyaluronic acid (Hyalgan/Polireumin; 2 ml = kda), and the group C.II animals were injected with 0.04 ml of the hyaluronic acid vehicle. The technique was performed with the knee flexed at 90 degrees. The needle was introduced perpendicularly to the skin and laterally to the patellar ligament, at the depression just above the joint line, in the direction of the intercondylar notch. Oral diacerein (50 mg/kg in a dilution with 0. g/l of evaporated milk) was administered to the animals in groups S.II and S.III, daily from the third postoperative month to the seventh month, until one day before these rats were sacrificed (28 th week). The animals were sacrificed by means of injection of intraperitoneal ketamine at a dose of 0 mg/kg in association with 0.8 mg/kg of diazepam. After sacrifice, both knees were removed, placed in 0% formaldehyde solution and then sent for histological analysis. The knees were kept in this solution for one day and then demineralized in 7.5% nitric acid for three days. Longitudinal slides of the distal femur and proximal tibia were stained with hematoxylin and eosin. The pathologist was blinded to the groups under analysis. Semi-quantitative histological changes were recorded in accordance with a table of arthritic alterations that was designed by the pathologist and co-author (CRGCMO), based on the studies by Moskowitz et al., 8 Colombo et al. 2,4 and Mazières et al. 6 (Table ). The arthritic grade was calculated by adding the points scored from the alterations seen on the slide. The final score defined the degree of arthritis in accordance with the following criteria: mild if the score was up to 2.5; moderate if the score was between 3 and 7; or severe if the score was between 7.5 and 0. Animals that died before the end of the experiment, or that, from histological evaluation, presented any disease that would interfere with the osteocartilaginous metabolism, were excluded from the study. Descriptive statistics on the ordinal (quantitative) sample values were calculated. The Mann-Whitney U-test was used in the comparisons between ordinal nonparametric and unrelated data, while the Wilcoxon test was used when the data were related (paired). The Kruskal-Wallis (variance analysis) test was used for comparison of more than two nonparametric strings. Pearson s correlation and regression tests were performed between ordinal strings. The significance level of 5% (a = 0.05) was chosen. RESULTS Seven animals died before the scheduled sacrifice date: three in group C.II and one each in groups C.I, C.III, C.IV and S.III. After sacrificing and slide analysis, one animal in group C.I was found to present plasmocytoma in both knees, and was excluded from the sample. A total of eight animals were excluded. Figure 2 shows the external and intra-articular macroscopic evaluations on the non-operated and operated non-medicated knees, 28 weeks after inclusion. Figures 3 and 4 show slides from the control and study groups. Figure. Medial meniscectomy by means of a medial access in a Wistar rat. Tibial collateral ligament is sectioned 3 mm from the joint line and retracted to expose the medial meniscus. After meniscectomy, the ligament is sutured with nylon 5-0. Table. Scoring system used to sum degenerative changes Lesions on slides Points Cloning of chondrocytes 0.5 Subchondral bone sclerosis 0.5 Surface fibrillation 0.5 Matrix degeneration 0.5 Superficial fissure 0.5 Fissure down to middle layer 0.5 Deep-layer fissure Matrix fibrillation Subchondral myxoid degeneration 2 Subchondral cyst 3 Sum 0 6 Sao Paulo Med J. 205; 33():4-2

11 Experimental osteoarthritis model by means of medial meniscectomy in rats and effects of diacerein administration and hyaluronic acid injection ORIGINAL ARTICLE A C Figure 2. Macroscopic appearance of non-operated and operated knees of Wistar rats at 0 months of age. Nonoperated (C.III group) external view (A) and internal view (B). Right operated knee and left non-operated knee (C.I group) external view (C) and internal view (D). Nylon stitches on the medial aspect of the knee. B D Tables 2, 3 and 4 summarize the degenerative changes found on the distal femur and proximal tibial of all groups. The proximal tibias of the meniscectomized knees had greater degenerative changes. Seven months (28 weeks) after surgery, the proximal tibia in the rats that were subjected to surgery but were not medicated showed a score corresponding to severe arthritis, i.e. 8.6 ± 2.3 (median 0; range 5 0, with a worst possible score of 0), while the group that received daily oral doses of diacerein from the third to the seventh postsurgical month scored 2 ± 2.9 (median ; third quartile 2; range 0.5-0) in the proximal tibia. All the groups that were operated on showed a statistically significant difference in degenerative changes between the operated and nonoperated sides, on the proximal tibia. In Table 5, we compared the degenerative changes in all groups. The differences were significant on the right side (operated knees: right femur, P = 0.008; and right tibia P = 0.000), between the groups. The degenerative changes (Tables 2, 4 and 5) to the tibias of rats that were subjected to operations but were not medicated and were sacrificed at 28 weeks scored 8.56 on average (median 0; severe arthritis). These results were significantly worse than those found in the tibias of rats sacrificed 2 weeks after surgery (score.75; mild arthritis by definition; P = 0.00) and significantly worse than those found in animals of the same age that were not subjected to operations (C.III; P = 0.00). Injection of hyaluronic acid diminished the degenerative changes found in the rat groups that were subjected to operations but not medicated (C.I x S.I; P = 0.03) and in the rat groups that were only injected with the vehicle of the hyaluronic A B C D E F Figure 3. Histology of the control groups of Wistar rats. (A) Normal histology (00x, hematoxylin and eosin, HE); (B) Severe arthritis of the tibia with erosion (arrows) and subchondral cyst (large arrow) (C.I group; 25 x, HE); (C) Severe arthritis with deep fissure and erosion (arrows) (C.I group; 00 x, HE); (D) Mild arthritis of the femoral surface (C.II group; 25 x, HE); (E) Non-operated knee from control group C.III showing natural aging process and cloning of chondrocytes; (F) Tibial surface 2 weeks after meniscectomy (C.IV group; 00 x, HE). Sao Paulo Med J. 205; 33():4-2 7

12 ORIGINAL ARTICLE Rezende MU, Hernandez AJ, Oliveira CRGCM, Bolliger Neto R A B C Figure 4. Histology of the study groups of Wistar rats. (A) tibial surface in S.I group with erosion (large arrow) and fibrillation (arrow); (B) Operated tibial condyle S.II group showing cloning of chondrocytes, matrix degeneration and superficial fissures; (C) Operated tibial condyle (S.III group) showing cloning of chondrocytes and matrix degeneration. acid (C.II x S.I; P = 0.03). Daily administration of oral diacerein from the 2 th to the 28 th week after surgery (S.II) showed significantly better results (average tibial degenerative changes of 2 points (median ) on the right side and 0.2 (median 0) on the non-operated side) compared with those that were operated but not medicated (C.I) (P = for the operated side and P = for the non-operated side; Table 5). S.II showed no statistically significant difference in the results obtained from the two knees (distal femur and proximal tibia) of the animals that were sacrificed at 2 weeks after surgery (time point at which the medication was delivered to group S.II), P = 0.32 (right distal femur); P = 0.09 (left distal femur); P = 0.38 (right proximal tibia) and P = 0.48 (left proximal tibia); Table 5. Furthermore, daily oral diacerein combined with intra-articular injection of hyaluronic acid did not show better results: P = (proximal right tibia). Daily oral diacerein led to better results than injection of hyaluronic acid given in the third and sixth month after surgery (right tibia, P = 0.009; right femur, P = 0.34). The initial animal weights ranged from ± 27. grams (C.III) to ± 5.6 grams (C.II) with no differences between the groups (P = 0.25). The final weights ranged from 470. ± 8.4 grams (C.IV) to ± 55.8 (S.I) with no particular difference between the groups (P = 0.36). None of the femoral changes correlated with the weight (either initial or final). The degenerative changes to the operated tibia, which were clinically more significant, showed no particular correlation with the animal s weight at the beginning of the study. The only significant association found in the study was a correlation between final weight (FW) and degenerative changes (DG) in the right tibia in group S.I. The linear regression equation for this was DG = x FW (P = 0.02). DISCUSSION The main goal of this study was to provide an animal model of secondary OA that would be suitable for testing drugs that might retard or reverse cartilage degradation. For this purpose, we tested two specific drugs. Table 2. Means and standard deviations of degenerative change scores for the femur and tibia in all groups Degenerative change scores Groups Femur Tibia Right Left Right Left C.I 3.06 ± ± ± ±.07 C.II.4 ± ± ± ±.27 C.III 0.50 ± ± 0.00 ± ±.37 C.IV 0.69 ± ± ± ± 0.26 S.I 2.6 ± ± ± ±.37 S.II 0.5 ± ± ± ± 0.26 S.III.00 ± ± ± ± 0.90 C.I = operated, non-medicated; C.II = operated, injections of HA vehicle; C.III = non-operated, non-medicated; C.IV = operated, non-medicated, sacrificed three months post-meniscectomy; S.I = operated, receiving intraarticular HA injections; S.II = operated, oral diacerein from the third to the seventh postoperative month; S.III = operated, received both medications. We proposed a new experimental model of secondary OA caused by total medial meniscectomy and ligament repair. In this model, young adult Wistar rats were subjected to total medial meniscectomy that had to be managed by means of sectioning and suturing the tibial collateral ligament. This is a slow but aggressive model of OA that leads to stiffness and severe degenerative changes, i.e. exposure of the subchondral bone and osteophyte formation seven months after the operation. We chose rats mainly because of the ease of working with 70 animals of a smaller size, but also because studies on rabbits that remained confined to cages showed better results with disease-modifying drugs 7 than studies on larger animals that were free to walk during the study. 5,8 Therefore, in this study, we used small animals that were free to walk during the nighttime. Male rats were chosen in order to avoid the effects of female hormones on joint degeneration. 9 According to Silberberg and Silberberg, 7 the degree in which OA develops in a fat-rich diet model depends on the lineage, gender, age at the introduction of the diet and the length of time for which this diet is given. Thus, we tried to reduce the number of variables as much as possible, so as to have a homogeneous set of animals, which was represented by the similar weight results. 8 Sao Paulo Med J. 205; 33():4-2

13 Experimental osteoarthritis model by means of medial meniscectomy in rats and effects of diacerein administration and hyaluronic acid injection ORIGINAL ARTICLE Table 3. Median, minimum, maximum and first and third quartiles (Q and Q3) of femoral degenerative change scores in all groups: comparison between right and left sides using Wilcoxon test (α = 0.05) Femur Groups Right Left Min Q Median Q 3 Max Min Q Median Q 3 Max P C.I C.II C.III < 0.05 C.IV S.I S.II S.III C.I = operated, non-medicated; C.II = operated, injections of HA vehicle; C.III = non-operated, non-medicated; C.IV = operated, non-medicated, sacrificed three months post-meniscectomy; S.I = operated, receiving intra-articular HA injections; S.II = operated, oral diacerein from the third to the seventh postoperative month; S.III = operated, received both medications; Min = minimum; Max = maximum. Table 4. Median, minimum, maximum and first and third quartiles (Q and Q3) of tibial degenerative change scores in all groups: comparison between right and left sides using Wilcoxon test (α = 0.05) Tibia Groups Right Left Min Q Median Q 3 Max Min Q Median Q 3 Max P C.I C.II C.III C.IV S.I S.II S.III C.I = operated, non-medicated; C.II = operated, injections of HA vehicle; C.III = non-operated, non-medicated; C.IV = operated, non-medicated, sacrificed three months post-meniscectomy; S.I = operated, receiving intra-articular HA injections; S.II = operated, oral diacerein from the third to the seventh postoperative month; S.III = operated, received both medications; Min = minimum; Max = maximum. In Tables 2, 3 and 4, we summarized the results from the degenerative changes found in the right operated and left non-operated knees. It is well known that as few as four animals per group may suffice for screening if the test drugs are highly effective. Otherwise, eight or more animals may be required. 2 Despite losses in almost all groups, we were able to establish the degenerative changes found three months after the operation (C.IV) and seven months after the operation (C.I), and also the natural aging process in the animals that did not undergo surgery (C.III). In this study, animals of approximately 0 months of age (C.III) had mild degenerative changes in both knees due to cloning of chondrocytes, superficial fissures, surface fibrillation and, in some cases, subchondral bone sclerosis and matrix degeneration. Animals that were subjected to surgery and sacrificed 2 weeks after meniscectomy, showed mild arthritis (mean and median score of.75) of the right knee (tibia) and almost no degenerative changes in the left knee (mean score = 0.9, median = 0), probably because the animals were young (between five and seven months of age) and because there had been little time for arthritis to affect the contralateral knee. 20 The animals in the C.I group showed the worst degenerative changes (8.56 in the right tibia and.9 in the left tibia). The degree of arthritis in the operated knee was significantly worse than among the animals sacrificed at 2 weeks (C.IV) and among the animals that were not subjected to surgery (P = 0.00 for both, in the right tibia; Tables 4 and 5). The degree of arthritis on the left side in the C.I group was significantly different from that of animals that did not undergo surgery (C.III) (P = 0.00) but the difference was not clinically relevant. Both groups had mild arthritis: mean score.9, median 0.75, in C.I; and mean.06, median 0.25, in C.III. Unilateral inflammation can induce distal bilateral degeneration of articular cartilage through neurogenic mechanisms, thus suggesting involvement of neuropeptides. 20 It is possible that if the study had been carried out for a longer period of time, a more relevant difference would have been shown between the non-operated side and the degenerative changes expected through aging. One of the questions in the present study was whether injection of hyaluronic acid ( kda, 0 mg/ml) once a week for five weeks in the third postoperative month and then two more weekly injections 2,22 in the sixth month (weeks 25 and 26) would Sao Paulo Med J. 205; 33():4-2 9

14 ORIGINAL ARTICLE Rezende MU, Hernandez AJ, Oliveira CRGCM, Bolliger Neto R delay or prevent degenerative changes in the operated knee. It is known that the half-life of hyaluronate in the joint is 3 hours, which leads to a residence time of about seven days in the joint. 2 The two extra injections in the sixth postoperative month were based on the study by Schiavinato et al., 22 so as to limit the period without any medication to a maximum of 0 weeks. Hyaluronic acid is known to have analgesic properties 23 and has been shown in some animal studies to prevent degenerative changes and stiffness caused by immobilization, ligament instability and meniscectomy, depending on the timing, dose and molecular weight. 0,7,8,22,24,25 In human studies, 26,27 it has been shown to relieve pain and increase function, and it may potentially delay the structural progression of the disease. In our study, the protection for the joint cartilage given through injection of hyaluronic acid (S.I group) was greater than what was achieved through injection of the vehicle for hyaluronic acid (Tables 2 to 5). Questions remain regarding the appropriate dose, frequency and type of hyaluronic acid that will yield better results. We injected 0.04 ml of hyaluronic acid or vehicle for hyaluronic acid. This dose is similar to the 0. ml/kg that were injected in rabbits or dogs in other studies. 7,8,28,29 However, the results were extremely heterogeneous. This may be due to several reasons, such as the degree of arthritis when the dose is initially injected, whether intra-articular injection of the medication was accomplished and whether the animal responded to the medication. In reality, injection of any medication is feasible in a normal rat s knee. Some animals, three months after surgery, already had stiffness and/or synovitis in the operated knee. Those animals were difficult to inject and had worse results. Three rats presented severe arthritis, scoring 0 points; three rats showed moderate arthritis scoring between 5 and 7; and four rats scored between and 2 (mild arthritis). Table 4 shows the scores for the group S.: first quartile (2), third quartile (0) and median (4.5). Table 3 shows the less pronounced femoral changes. Although on average injection of hyaluronic acid modified the course of post-meniscectomy osteoarthritis, this may not have been the best experimental model for testing intra-articular medications. Because of the already-mentioned possibility that unilateral inflammation could induce distal bilateral degeneration of joint cartilage via neurogenic mechanisms, 20 the idea of an oral medication with the possibility of disease-modifying effect is quite appealing. Diacerein (and its active derived metabolite rhein) is an anthraquinone disulfonic acid disease-modifying osteoarthritis drug. It has been shown in vitro to inhibit dose-dependent cathepsin B activity and time and dose-dependent interleukin- -beta-stimulated proteoglycan release from the cartilage matrix; and in vivo to reduce all cartilage degeneration parameters and joint stiffness. 6,30 It modulates the expression of matrix-degrading Table 5. Comparison of degenerative change scores between groups for each side and bone end of the knee joint: overall comparison using Kruskal-Wallis test (α = 0.05) and comparison between group pairs using Mann-Whitney U test (α = 0.05) Groups Right femur Left femur Right tibia Left tibia Overall C.I versus C.II C.I versus C.III C.I versus C.IV C.I versus S.I C.I versus S.II C.I versus S.III C.II versus C.III C.II versus C.IV C.II versus S.I C.II versus S.II C.II versus S.III C.III versus C.IV C.III versus S.I C.III versus S.II C.III versus S.III C.IV versus S.I C.IV versus S.II C.IV versus S.III S.I versus S.II S.I versus S.III S.II versus S.III C.I = operated, non-medicated; C.II = operated, injections of HA vehicle; C.III = non-operated, non-medicated; C.IV = operated, non-medicated, sacrificed three months post-meniscectomy; S.I = operated, receiving intraarticular HA injections; S.II = operated, oral diacerein from the third to the seventh postoperative month; S.III = operated, received both medications. enzymes and cell proliferation of articular chondrocytes through inhibiting ERK and JNK-AP- dependent pathways. 3 It downregulates pro-inflammatory cytokine expression (interleukin--beta (IL-b), IL-2 and TNF-alpha). 32 In this study, the animals that received 50 mg/kg of oral diacerein daily from the third to the seventh postoperative month showed the best results on all slides (femur and tibia bilaterally, whether operated on or not). There was no difference between the findings seven months after surgery in the group that received daily doses of diacerein and the group that was sacrificed three months after the operation. Diacerein prevented progression of osteoarthritis in the operated knee and the normal age-related or even neurogenic mediated arthritis of the contralateral side (Tables 2 to 5). The combination of oral diacerein and injection of hyaluronic acid did not improve the results obtained through an oral dose of diacerein alone (Tables 2 to 5). These results were not affected by the animal s weight. However, none of the animals were obese and they all had similar weights. 0 Sao Paulo Med J. 205; 33():4-2

15 Experimental osteoarthritis model by means of medial meniscectomy in rats and effects of diacerein administration and hyaluronic acid injection ORIGINAL ARTICLE The meniscectomy osteoarthritic model in rats proved to be a useful model for testing osteoarthritis disease-modifying drugs. The limitations of the study relate mainly to the histological analysis, which was mostly done using hematoxylin-eosin, thereby missing early matrix changes, and the short follow-up. Future goals would include improvement of histological analysis and testing of other disease-modifying osteoarthritic drugs. CONCLUSIONS ) The meniscectomy experimental model in rats presented here was effective in producing mild arthritis three months postoperatively and severe arthritis seven months postoperatively; 2) oral diacerein was effective in reducing the degenerative changes in both knees; 3) there was some protection for joint cartilage through intermittent intra-articular injection of hyaluronic acid; 4) using the two drugs in association did not improve the results. REFERENCES. 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. 986;29(8): Colombo C, Butler M, O Byrne E, et al. A new model of osteoarthritis in rabbits. I. Development of knee joint pathology following lateral meniscectomy and section of the fibular collateral and sesamoid ligaments. Arthritis Rheum. 983;26(7): 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 Osteoarthritis Cartilage. 200;8(4): Setnikar I. Antireactive properties of chondroprotective drugs. Int J Tissue React. 992;4(5): Ghosh P, Read R, Numata Y, et al. The effects of intraarticular administration of hyaluronan in a model of early osteoarthritis in sheep. II. Cartilage composition and proteoglycan metabolism. Semin Arthritis Rheum. 993;22(6 Suppl ): Savarino L, Fioravanti A, Leo G, Aloisi R, Mian M. Anthraquinone-2,6- disulfonic acid as a disease-modifying osteoarthritis drug: an in vitro and in vivo study. Clin Orthop Relat Res. 2007;46: Silberberg M, Silberberg R. Osteoarthrosis in mice fed diets enriched with animal or vegetable fat. Arch Pathol. 960;70: Moskowitz RW, Davis W, Sammarco J, et al. Experimentally induced degenerative joint lesions following partial meniscectomy in the rabbit. Arthritis Rheum. 973;6(3): Marshall JL. Periarticular osteophytes. Initiation and formation in the knee of the dog. Clin Orthop Relat Res. 969;62: Pond MJ, Nuki G. Experimentally-induced osteoarthritis in the dog. Ann Rheum Dis. 973;32(4): Cake M, Read R, Edwards S, et al. Changes in gait after bilateral meniscectomy in sheep: effect of two hyaluronan preparations. J Orthop Sci. 2008;3(6): Cox JS, Nye CE, Schaefer WW, Woodstein IJ. The degenerative effects of partial and total resection of the medial meniscus in dogs knees. Clin Orthop Relat Res. 975;(09): Shapiro F, Glimcher MJ. Induction of osteoarthrosis in the rabbit knee joint. Clin Orthop Relat Res. 980;(47): Colombo C, Butler M, Hickman L, et al. A new model of osteoarthritis in rabbits. II. Evaluation of anti-osteoarthritic effects of selected antirheumatic drugs administered systemically. Arthritis Rheum. 983;26(9): Butler M, Colombo C, Hickman L, et al. A new model of osteoarthritis in rabbits. III. Evaluation of anti-osteoarthritic effects of selected drugs administered intraarticularly. Arthritis Rheum. 983;26(): Mazières B, Berdah L, Thiéchart M, Viguier G. [Diacetylrhein on a postcontusion model of experimental osteoarthritis in the rabbit]. Rev Rhum Ed Fr. 993;60(6 Pt 2):77S-8S. 7. Sakakibara Y, Miura T, Iwata H, et al. Effect of high-molecular-weight sodium hyaluronate on immobilized rabbit knee. Clin Orthop Relat Res. 994;(299): Smith GN Jr, Myers SL, Brandt KD, Mickler EA. Effect of intraarticular hyaluronan injection in experimental canine osteoarthritis. Arthritis Rheum. 998;4(6): Rosner IA, Goldberg VM, Getzy L, Moskowitz RW. Effects of estrogen on cartilage and experimentally induced osteoarthritis. Arthritis Rheum. 979;22(): Decaris E, Guingamp C, Chat M, et al. Evidence for neurogenic transmission inducing degenerative cartilage damage distant from local inflammation. Arthritis Rheum. 999;42(9): Brandt KD, Smith GN Jr, Simon LS. Intraarticular injection of hyaluronan as treatment for knee osteoarthritis: what is the evidence? Arthritis Rheum. 2000;43(6): Schiavinato A, Lini E, Guidolin D, et al. Intraarticular sodium hyaluronate injections in the Pond-Nuki experimental model of osteoarthritis in dogs. II. Morphological findings. Clin Orthop Relat Res. 989;(24): Gomis A, Miralles A, Schmidt RF, Belmonte C. Intra-articular injections of hyaluronan solutions of different elastoviscosity reduce nociceptive nerve activity in a model of osteoarthritic knee joint of the guinea pig. Osteoarthritis Cartilage. 2009;7(6): Amiel D, Frey C, Woo SL, Harwood F, Akeson W. Value of hyaluronic acid in the prevention of contracture formation. Clin Orthop Relat Res. 985;(96): Hsieh YS, Yang SF, Lue KH, Chu SC, Lu KH. Effects of different molecular weight hyaluronan products on the expression of urokinase plasminogen activator and inhibitor and gelatinases during the early stage of osteoarthritis. J Orthop Res. 2008;26(4): Sao Paulo Med J. 205; 33():4-2

16 ORIGINAL ARTICLE Rezende MU, Hernandez AJ, Oliveira CRGCM, Bolliger Neto R 26. Listrat V, Ayral X, Patarnello F, et al. Arthroscopic evaluation of potential structure modifying activity of hyaluronan (Hyalgan) in osteoarthritis of the knee. Osteoarthritis Cartilage. 997;5(3): Guidolin DD, Ronchetti IP, Lini E, Guerra D, Frizziero L. Morphological analysis of articular cartilage biopsies from a randomized, clinical study comparing the effects of kda sodium hyaluronate (Hyalgan) and methylprednisolone acetate on primary osteoarthritis of the knee. Osteoarthritis Cartilage. 200;9(4): Yoshimi T, Kikuchi T, Obara T, et al. Effects of high-molecular-weight sodium hyaluronate on experimental osteoarthosis induced by the resection of rabbit anterior cruciate ligament. Clin Orthop Relat Res. 994;(298): Williams JM, Plaza V, Hui F, et al. Hyaluronic acid suppresses fibronectin fragment mediated cartilage chondrolysis: II. In vivo. Osteoarthritis Cartilage. 997;5(4): Rezende MU, Gurgel HM, Vilaça Junior PR, et al. Diacerhein versus glucosamine in a rat model of osteoarthritis. Clinics (Sao Paulo). 2006;6(5): Legendre F, Bogdanowicz P, Martin G, et al. Rhein, a diacerheinderived metabolite, modulates the expression of matrix degrading enzymes and the cell proliferation of articular chondrocytes by inhibiting ERK and JNK-AP- dependent pathways. Clin Exp Rheumatol. 2007;25(4): Malaguti C, Vilella CA, Vieira KP, et al. Diacerhein downregulate proinflammatory cytokines expression and decrease the autoimmune diabetes frequency in nonobese diabetic (NOD) mice. Int Immunopharmacol. 2008;8(6): Sources of funding: None Conflict of interest: None Date of first submission: February 8, 203 Last received: September 30, 203 Accepted: December 3, 203 Address for correspondence: Marcia Uchôa Rezende Rua Dr. Ovídio Pires de Campos, 333 Cerqueira César São Paulo (SP) Brasil CEP Tel. (+ 55 ) Sao Paulo Med J. 205; 33():4-2

17 DOI: 0.590/ ORIGINAL ARTICLE Lateral wedge insole for knee osteoarthritis: randomized clinical trial Palmilha valgizante para osteoartrite de joelhos: ensaio clínico randomizado Gustavo Constantino de Campos I, Marcia Uchôa Rezende II, Thiago Pasqualin III, Renato Frucchi III, Raul Bolliger Neto IV Institute of Orthopedics and Traumatology, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, Brazil I MD. Doctoral Student, Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, Brazil. II MD, MSc, PhD. Head of Osteometabolic Disease Group, Hospital das Clínicas (HC), Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, Brazil. III MD. Medical Volunteer, Osteometabolic Disease Group, Hospital das Clínicas (HC), Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, Brazil. IV MD, MSc, PhD. Attending Physician in Institute of Orthopedics and Traumatology, Hospital das Clínicas (HC), Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, Brazil. KEY WORDS: Osteoarthritis. Orthotic devices. Randomized controlled trial [publication type]. Orthopedics. Knee joint. PALAVRAS-CHAVE: Osteoartrite. Aparelhos ortopédicos. Ensaio clínico controlado aleatório. Ortopedia. Articulação do joelho. ABSTRACT CONTEXT AND OBJECTIVE: Optimal management of knee osteoarthritis requires a combination of pharmacological and non-pharmacological methods. The use of lateral wedge insoles to treat medial knee osteoarthritis is recommended, but there is still controversy about its efficacy. The purpose of this study was to ascertain whether the use of lateral wedge insoles can diminish pain and improve function in patients with medial knee osteoarthritis. DESIGN AND SETTING: Prospective randomized trial conducted in a tertiary-level hospital. METHODS: We prospectively enrolled 58 patients with medial knee osteoarthritis and randomized them to use either a lateral wedge insole with subtalar strapping (Group W), or a neutral insole with subtalar strapping (Group N - control). All the patients were instructed to use the insole for five to ten hours per day. A visual analogue pain scale, the Western Ontario and McMaster Universities Arthritis Index (WOMAC) and the Lequesne questionnaire were applied at baseline and at weeks 2, 8 and 24. RESULTS: At weeks 8 and 24, both groups showed lower scores for WOMAC (P = 0,023 and P = 0,02 respectively). There were no statistically significant differences between the groups regarding the visual analogue pain scale, WOMAC or Lequesne results at any time evaluated. CONCLUSION: The use of a lateral wedge insole with subtalar strapping improved the patients symptoms and function but was not superior to placebo insoles. CLINICAL TRIAL REGISTRATION: NCT RESUMO CONTEXTO E OBJETIVO: O manejo ideal da osteoartrite de joelhos requer combinação entre modalidades farmacológicas e não farmacológicas. O uso de palmilhas valgizantes no tratamento da osteoartrite medial do joelho é recomendado, mas sua eficácia ainda é controversa. Este estudo objetiva verificar se o uso da palmilha valgizante pode diminuir a dor e melhorar a função dos pacientes com osteoartrite medial dos joelhos. DESENHO E LOCAL: Ensaio clínico prospectivo e randomizado conduzido em hospital de atenção terciária. MÉTODOS: Alocamos prospectivamente 58 pacientes com osteoartrite medial dos joelhos que foram randomizados para fazer uso de palmilha valgizante com amarrilho subtalar (Grupo W) ou palmilha neutra com amarrilho subtalar (Grupo N - controle). Todos os pacientes foram orientados a utilizar a palmilha entre cinco e dez horas por dia. Foram aplicados os questionários Western Ontario and McMaster Universities Arthritis Index (WOMAC) e Lequesne, além da escala visual analógica da dor, nos momentos pré e após 2, 8 e 24 semanas. RESULTADOS: Após 8 e 24 semanas, ambos os grupos apresentaram redução dos valores de WOMAC (P = 0,023 e P = 0,02 respectivamente). Não houve diferença estatisticamente significativa entre os grupos nos resultados de WOMAC, Lequesne e escala visual analógica de dor, em nenhum dos momentos avaliados. CONCLUSÃO: O uso de palmilha valgizante com amarrilho subtalar melhorou os sintomas e a função dos pacientes, mas não foi melhor que placebo. REGISTRO DE ENSAIO CLÍNICO: NCT Sao Paulo Med J. 205; 33():3-9 3

18 ORIGINAL ARTICLE Campos GC, Rezende MU, Pasqualin T, Frucchi R, Bolliger Neto R INTRODUCTION Osteoarthritis is a major cause of chronic musculoskeletal pain and disability in the elderly population. Knee osteoarthritis is one of the most common forms of osteoarthritis and the most frequent chronic condition that leads to functional limitation in older adults, affecting more people than any other joint disease. 2 Recent guidelines recommend that optimal management of osteoarthritis requires a combination of non-pharmacological and pharmacological methods. 3 All patients should be given access to information and education about the objectives of treatment and the importance of changes in lifestyle, exercise, pacing of activities, weight reduction and other measures to reduce the load on the damaged joint(s), such as walking aids, knee braces and insoles, as well as muscle strengthening and weight loss. 3 Involvement of the medial compartment of the knee is ten times more common than involvement of the lateral compartment. 4,5 Knee osteoarthritis in the medial compartment is strongly associated with biomechanical factors, particularly progressive varus deformity, which systematically increases the load on the medial compartment, thus further increasing the risk of damage to this compartment. 6,7 Biomechanical and clinical studies have shown that lateral wedge insoles can promote a reduction in the adduction moment of 4 to 2% during gait, thus reducing the load on the medial knee compartment 8-0 and promoting symptomatic benefit for some patients with medial compartment tibiofemoral osteoarthritis. The use of lateral wedged insoles for patients with medial compartment knee osteoarthritis is certainly a very interesting treatment option because of its low cost, low complexity and virtually absence of side effects. 2,3 However, apart from Japan, where several studies have demonstrated its efficacy, 0,4-6 the recent literature on the use of lateral wedges for medial compartment knee osteoarthritis is insufficient to draw any substantial conclusions. Two recent systematic reviews have shown limited evidence to support the use of lateral wedge orthotics for reducing pain, increasing function or slowing disease progression. 7,8 Eligibility criteria The eligibility criteria were that patients needed to meet the American College of Rheumatology criteria for knee osteoarthritis 9 and to present varus malalignment of the knee; absence of hip osteoarthritis; absence of ankle pain; absence of previous fracture on the index knee; absence of previous surgery on the index knee; absence of rheumatoid arthritis; and lack of intra-articular injection in the index knee in the past six months. The patients also needed to have been receiving the usual care for osteoarthritis for at least six months and to be able to understand and agree with the informed consent statement. Exclusion criteria The exclusion criteria for this study were: - Undergoing surgery during the study period. - Undergoing intra-articular injection during the study period. - Developing infection of the index joint during the study period. One hundred and thirty-eight patients were interviewed, and fifty-eight patients met the inclusion criteria (Figure ). All the patients in our department receive the same treatment protocol, which we call the usual care for knee osteoarthritis. Enrollment Eligibility Allocation Follow-up Patients interviewed (n = 38) Met inclusion criteria (n = 58) Week Zero n = 29 Randomization Week Zero n = 29 OBJECTIVE The purpose of this study was to ascertain whether the use of lateral wedge insoles can diminish pain and improve function in patients with medial knee osteoarthritis. METHODS This prospective single-blind parallel group controlled trial was conducted under the principles of the Helsinki Declaration and was approved by CAPPesq (Ethics Committee for analysis of research projects) under the protocol number 839/20. It followed the CONSORT (Consolidated Standards of Reporting Trials) Statement and evaluated 58 patients with knee osteoarthritis (Figure ). It was registered at clinicaltrials.gov under the number NCT Figure. Study flow diagram. Week 2 n = 29 Week 8 n = 29 Week 24 n = 29 Week 2 n = 29 Week 8 n = 29 Week 24 n = 29 Statistical analysis (n = 58) 4 Sao Paulo Med J. 205; 33():3-9

19 Lateral wedge insole for knee osteoarthritis: randomized clinical trial ORIGINAL ARTICLE The usual care consists of patient education through lectures, handouts, audiovisual material and guidance given by orthopedic surgeons, nutritionists, psychologists, occupational therapists, physical therapists, physical educators and social workers. All patients, except those with contraindications, take analgesics (on demand), such as paracetamol and codeine. We do not routinely give non-steroidal anti-inflammatory drug (NSAIDs) to our patients. All the patients invited to participate in the present study agreed to do so. The study was conducted in an outpatient setting at a tertiary hospital. One week before start to use the orthotic devices, the patients who met the criteria gave responses on the visual analogue scale for pain (VAS) and to the Western Ontario and McMaster Universities Arthritis Index (WOMAC) 20 and Lequesne questionnaire. 2 Anthropometric data was also collected, such as age, gender, race, height, weight and body mass index (BMI). Plain radiographs of the knees were available for all the patients, in anteroposterior view with unilateral weight bearing and in lateral and patellar axial views. Three of us (GCC, TP, RF) examined all the radiographs in order to classify the severity of the osteoarthritis using the Kellgren-Lawrence scheme. 22 In 8 cases, there was interobserver disagreement. In all of these cases, we took into consideration the classification level given by the majority (two observers). None of the radiographs resulted in total discordance (three different classifications). The patients were randomly divided into two groups of 29 patients by means of simple randomization. The randomization was performed using a computer-generated program (available from: and was done by an investigator who did not have any involvement in the rest of the study. The patients were confidentially allocated to the lateral wedge insole group (Group W) or the neutral insole group (Group N). Although the patients did not know which group they were in, they were not considered to be blind to this, since they could see the shape of the insole. All the patients used insoles on both feet. Group W patients with unilateral knee osteoarthritis used a lateral wedge insole on the affected limb and a neutral insole on the contralateral limb. Group W patients with bilateral disease used a lateral wedge insole on both limbs. Group N patients used a neutral insole on both limbs. The wedge insoles were made with a full length lateral wedge of 8 mm (equivalent to about eight degrees of inclination) attached to a figure eight strap around the ankle (Figure 2). The neutral insoles were exactly the same orthosis, but without a lateral wedge. All the patients were encouraged to use the insoles for 5-0 hours per day. The VAS, WOMAC and Lequesne questionnaires were again applied during scheduled visits in weeks two, eight and 24. The primary outcomes measured were knee pain and knee function improvement, which were expressed through the results of the questionnaires applied. The secondary outcomes were the presence of adverse effects (such as ankle pain) and any correlation between anthropometric data and clinical outcomes. The sample size was estimated by calculating n such that it enabled statistical power of 80% and a significance level of 5%. For the primary outcome of VAS, we took the standard deviation (SD) of.9 that had been found in a previous study 23 and stipulated that the difference to be detected should be at least.5 points. Using a two-tailed hypothesis test, we found that the number of patients per group should be 25. Taking estimates of 20% for dropouts and exclusions, we calculated that 29 patients per group were needed. B Figure 2. Insoles. (A) Full length ethylene vinyl acetate (EVA) insole attached to an ankle-sprain support; (B) lateral wedge insole (Group W); (C) neutral insole (Group N); (D) patient wearing a lateral wedge insole. The investigator (MUR) who applied the questionnaires was blinded (unaware of the patient s group). To determine whether the groups differed with regard to the nominal variables, we used absolute and relative frequencies, and checked for associations using chi-square for gender and the likelihood ratio for race. The Mann-Whitney test was used to compare groups regarding A C D Sao Paulo Med J. 205; 33():3-9 5

20 ORIGINAL ARTICLE Campos GC, Rezende MU, Pasqualin T, Frucchi R, Bolliger Neto R the Kellgren-Lawrence grade. The quantitative characteristics were described in groups through using summary measurements (mean, SD, median, minimum and maximum), and the groups were compared using Student s t-test. We used a significance level of 5% for all analyses. RESULTS The patients were recruited between June 20 and July 20. Twenty-nine patients were randomly assigned to each group, received the intended treatment and were analyzed for functional and pain status using VAS and the WOMAC and Lequesne questionnaires. All the patients were evaluated clinically and started using the lateral wedge insoles between August 20 and September 20. The trial ended in March 202, in week 24 of the follow-up. There were no losses. There were no differences between the groups in relation to nominal and numerical characteristics (Table ) or scores (Table 2) at baseline. Scales were also described as groups and times through using summary measurements (Table 3). The relationships among the results were analyzed using Pearson s correlations regarding numerical characteristics such as age and body mass index (BMI) and using Spearman s correlation regarding Kellgren-Lawrence grade (Table 4). At weeks 8 and 24, both groups showed lower results for WOMAC, with a difference from baseline (P = and P = 0.02 respectively). The mean WOMAC pain subscale score showed statistically significant reductions at all times. in comparison with the baseline, in both groups (P < 0.05). There was no difference between the groups at any time regarding any score (Table 3). There was no correlation between anthropometric data and the clinical outcomes (Table 4). Fifteen percent of all the patients reported ankle discomfort (Table 5). One patient in the W group abandoned the treatment due to ankle pain. There were no differences between the groups regarding adverse effects. DISCUSSION Biomechanical and clinical studies have shown that lateral wedge insoles can promote a reduction in the load on the medial knee compartment 8-0 and symptomatic benefits for patients with medial knee osteoarthritis.,24 Likewise, medial wedge insoles have shown benefits for patients with lateral compartment knee osteoarthritis. 25 However, despite recommendations in several guidelines, 26 neither the present study nor some long-term studies in the literature found any clinical benefit. 7,8,23,27 To the best of our knowledge, our study is the first clinical trial on lateral wedge insoles in a South American population. Our study has some limitations. First, we did not limit the use of analgesics or any other non-pharmacological treatment. We believe that use of insoles should not exclude any other type of treatment, and therefore, the patients received their usual care but were asked to keep track of their use of analgesics. No differences were found between the groups in this regard. Second, clinical scores such as WOMAC and Lequesne cannot distinguish one knee from another when the patient has bilateral osteoarthritis. Therefore, patients with bilateral disease had both knees treated and only the knee that was Table. Baseline demographics Variable Study group (n = 29) Control group (n = 29) Total (n = 58) Gender n (%) Male (37.9) 0 (34.5) 2 (36.2) Female 8 (62.) 9 (65.5) 37 (63.8) 0.785* Race n (%) Asian (3.4) (3.4) 2 (3.4) White 20 (69) 23 (79.3) 43 (74.) Black 3 (0.3) 3 (0.3) 6 (0.3) Mixed 5 (7.2) 2 (6.9) 7 (2.) Kellgren-Lawrence n (%) Grade 2 (6.9) 2 (6.9) 4 (6.9) Grade 2 9 (3) 0 (34.5) 9 (32.8) Grade 3 5 (7.2) 8 (27.6) 3 (22.4) 0.48 Grade 4 3 (44.8) 9 (3) 22 (37.9) Age (years) Mean (SD) 65.2 (9.6) 63.3 (7.5) 64.3 (8.6) Weight (kg) Mean (SD) 80.9 (7.5) 79.4 (3.6) 80.2 (5.5) 0.70 Height (m) Mean (SD).6 (0.).6 (0.).6 (0.) 0.95 BMI (kg/m 2 ) Mean(SD) 30.8 (6.) 30.3 (5.) 30.6 (5.6) P-values from: Student s t test; *chi-square test; likelihood ratio; Mann-Whitney test Table 2. Scores according to groups and times Variable WOMAC WOMAC pain subscale VAS Lequesne Time Group W (n = 29) Group N (n = 29) P Total (n = 58) Week zero 46. (9.7) 50.2 (2.) 48. (20.4) Week (7.8) 43.0 (9.6) 44.2 (8.6) Week (9.5) 43.7 (9.5) 43.3 (9.3) Week (9.3) 4.7 (22.) 40.3 (20.6) Week zero 9.3 (4.0) 0.3 (4.4) 9.8 (4.2) Week (3.4) 8.4 (3.6) 8.7 (3.5) Week (3.4) 8.7 (4.) 8.3 (4.2) Week (3.8) 8.3 (4.7) 8.3 (4.2) Week zero 59.8 (26.6) 65.9 (26.) 62.9 (26.3) Week (26.0) 55.5 (26.0) 56.7 (25.8) Week (22.2) 55.2 (23.2) 54.7 (23.4) Week (22.4) 55.8 (24.7) 54.7 (23.4) Week zero 3.4 (3.6).8 (4.8) 2.6 (4.3) Week (3.).2 (4.3) 2.6 (4.3) Week (3.5).3 (4.3).8 (3.9) Week 24.9 (4.3) 0.8 (4.6).3 (4.4) WOMAC = Western Ontario and McMaster Universities Arthritis Index; VAS = visual analogue scale. 6 Sao Paulo Med J. 205; 33():3-9

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