All the authors declare that there is no potential conflict of interest referring to this article.

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1 DOI: htt://dx.doi.org/ / Original Article INTENSITY, DURATION AND TYPE OF PHYSICAL ACTIVITY REQUIRED TO IMPROVE FUNCTION IN KNEE OSTEOARTHRITIS INTENSIDADE, DURAÇÃO E TIPO DE ATIVIDADE FÍSICA PARA MELHORA DA FUNÇÃO NA GONARTRITE Ricardo Akihiro Kirihara 1, Fellie Bravim Catelan 1, Fabiane Elize Sabino de Farias 1, Cleidnéia Aarecida Clemente da Silva 1, Claudia Helena de Azevedo Cernigoy 1, Márcia Uchoa de Rezende 1 1. Universidade de São Paulo, Faculdade de Medicina, Hosital das Clinicas, Instituto de Ortoedia e Traumatologia, São Paulo, Brazil. ABSTRACT Objective: To evaluate the effects of hysical activity intensity, tye and duration in atients with knee osteoarthritis (KOA). Methods: A retrosective study of 5 KOA atients who were followed for two years after receiving educational material about KOA with or without attending classes. The atients were evaluated at baseline and 24 months. At the evaluations, the atients answered questionnaires ertaining to ain and function (WOMAC,, and SF-6); reorted the intensity, duration and tye of exercise erformed er week; and erformed the Timed U & Go (TUG) and Five Times Sit-to-Stand (FTSST) tests. Results: Increased age affected imrovements in the TUG results (=0.01). The tye, intensity and duration of hysical activity did not correlate with ain, function or quality of life imrovements (>0.05), but the TUG results were on average 4 seconds faster among the atients who racticed intense hysical activity and/or exercised for more than 180 minutes er week and/or erformed isolated weight training or swam comared with those who remained sedentary after 2 years (=0.01; <0.001; =0.01; =0.04, resectively). Conclusions: Patients with KOA should aim for intense hysical activity and/or more than 180 minutes of exercise er week and/or weight training (bodybuilding) for relevant ain reduction and functional imrovement. Level of Evidence II, Retrosective Study. Keywords: Osteoarthritis. Knee. Patient education as toic. Motor activity. Treatment outcome. RESUMO Objetivo: Avaliar o efeito da intensidade, tio e temo da atividade física semanal em acientes com osteoartrite do joelho (OAJ). Métodos: Cento e noventa e cinco acientes ortadores de OAJ foram acomanhados or dois anos aós receberam material educacional sobre OAJ, com ou sem aulas. Os acientes resonderam aos questionários de dor, função, qualidade de vida (WOMAC,, EVA e SF-6), intensidade, frequência e tio de atividade física semanal realizada, além de realizaram os testes de senta e levanta (TSL) e Timed-U-and-Go (TUG) no momento da inclusão e aós 24 meses. Resultados: O aumento da idade dos acientes acarretou menor chance de melhora no TUG (=0,01). O tio de atividade física, intensidade e frequência não mostraram correlação com melhoras algo-funcionais e de qualidade de vida (>0,05), orém os resultados do TUG foram em média 4 seg mais ráidos em acientes que raticavam atividade física intensa e/ ou acima de 180 min or semana e/ou musculação isolada, ou ainda, musculação ou natação, em relação aos acientes sedentários (=0,01; <0,001; =0,01; =0,04, resectivamente) aós dois anos. Pacientes raticantes de musculação tinham menos dor que os sedentários aós o rograma (=0,009). Conclusão: Pacientes com OAJ são aconselhados a objetivar atividade física intensa e/ou acima de 180 min or semana e/ou musculação ara atingir melhora algo-funcional relevante. Nível de Evidência II, Estudo Retrosectivo. Descritores: Osteoartrite. Joelho. Educação de acientes como assunto. Atividade motora. Resultado do tratamento. Citation: Kirihara RA, Catelan FB, Farias FES, Silva CAC, Cernigoy CHA, Rezende MU. Intensity, duration and tye of hysical activity required to imrove function in knee osteoarthritis. Acta Orto Bras. [online]. 1;25(1):25-9. Available from URL: htt:// INTRODUCTION Osteoarthritis is the leading cause of disability among chronic diseases. 1- The societal and ersonal costs of functional limitation resulting from osteoarthritis are high among older adults. 4,5 Medical exenses among the elderly are more closely related to functional losses than to life exectancy. 6, A lack of regular vigorous hysical activity is a otentially modifiable risk factor that could substantially reduce functional decline and related health care costs. Prevention/intervention rograms should include regular vigorous hysical activity, weight maintenance, and medical intervention for health needs. 8 We develoed an educational rogram for atients with knee osteoarthritis (KOA) that led to functional imrovement and increased adherence to regular hysical activity. 9,10 However, the intensity, duration and tye of hysical activity that is necessary to roduce significant functional gains is still unknown. Based on this need, we searched for a correlation between ain, functional and quality of life imrovements and absolute results and the intensity, duration All the authors declare that there is no otential conflict of interest referring to this article. Study conducted at Universidade de São Paulo, Faculdade de Medicina, Deartment of Orthoedics and Traumatology, Laboratório de Investigação Médica do Sistema Musculoesquelético, Osteometabolic Diseases Grou, São Paulo, SP, Brazil. Corresondence: Márcia Uchoa de Rezende. Rua Dr. Ovídio Pires de Camos,, Cerqueira César, São Paulo, SP, Brasil murezende@uol.com.br Article received in 0/05/16, aroved in 08/1/16. Acta Orto Bras. 1;25(1):

2 26 and tye of hysical activity racticed by atients to determine a hysical activity goal that would allow atients with KOA to obtain clinically relevant functional imrovements. METHODS This study was erformed at the Deartment of Orthoedics and Traumatology, São Paulo, Brazil, after it was aroved by the Ethics Committee for the Analysis of Research Projects (CAPPesq) under rotocol number 0622/11. Clinical trials registration number: NCT One hundred ninety-five atients with KOA (46 men, 1 women, age 68 ± 9.2 years and BMI 1.1 ± 5.4 at inclusion) who articiated in a two-year educational rogram for atients with KOA at the Osteometabolic Diseases Grou Deartment of Orthoedics, Hosital das Clínicas, University of São Paulo articiated in this study. The atients had to meet the following criteria: outatients who were aged 45 years or older with KOA diagnosed according to the American College of Rheumatology clinical and radiological definition, 11 had no rheumatoid arthritis or rheumatologic disease other than OA, had been receiving clinical treatment for OA in the ast thirty months and had articiated in the PARQVE educational rogram for atients with OAJ. 9,10 The exclusion criteria were 1) KOA surgery during the study eriod or other surgery during the study eriod that would revent regular hysical activity, and 2) articiation in another nutritional education rogram or another clinical study. Patients who were not able to erform or did not attend the functional tests were excluded only from the functional analysis. Intervention At enrollment and 24 months later, the atients were asked to resond to (visual analog ain scale), WOMAC,, and SF-6 questionnaires and to reort the duration, intensity and tye of hysical activity they erformed each week. -15 The atients were asked to erform the timed u-and-go (TUG) test and the five times sit-to-stand (FTSST) test All of the articiants received information on OA disease and its treatment in the form of classes and/or educational materials that included the class content in text and video (DVD) form. 9,10 The DVD was 2 hours and 2 minutes long. All of the atients were instructed to watch the DVD and/or read the handout at least three times and to exercise under the guidance of hysical theraists or hysical educators (via information of the handout or at ublic or rivate gyms) at least three times a week. Statistical analysis Imrovement criteria were established for each of the scores and functionality testing: a reduction of at least 10 oints on the total WOMAC score, 4 oints on the WOMAC ain score, 2 oints on the score, 5 oints on the WOMAC hysical function score, 4 seconds on the TUG and 4 seconds on the TSL. The quantitative characteristics were described as imrovement for each criterion with the use of summary measures (mean, standard deviation, median, minimum and maximum) and were comared using Student s t or Mann-Whitney tests. Imrovements in each criterion were described according to their qualitative characteristics and association using likelihood ratios or chi-square tests. Odds ratios (ORs) were estimated for the association between each variable of interest and imrovement in each criterion along with the resective 95% confidence intervals, based on simle logistic regression. Multile saturated logistic regression models were estimated for each of the imrovement criteria. The tests were erformed at the 5% significance level. RESULTS There was no relationshi between imrovement in the WOMAC,,, SF-6, TUG and FTSST scores and the tye, intensity and duration of hysical activity (all > 0.05). Table 1 shows that increasing age was associated with a lower likelihood of imrovement in the TUG score, regardless of the other characteristics evaluated. With each additional year of age, there was a % reduction in the chance of imrovement on the TUG test, OR = 0.9, = When comaring atients who engaged in intense hysical activity with those who did not engage in any hysical activity, we found that at enrollment, the few (three) atients who racticed intense hysical activity had less ain than the 15 sedentary atients (=0.02). After two years of articiating in the PARQVE 9,10 rogram, the atients who racticed intense hysical activity comleted the TUG an average of 4 seconds faster than the sedentary grou ( = 0.01, Table 2) and reorted less ain (50.9±15.) than those who did not engage in any hysical activity (59.4±2.1) but not significantly (Table 2). After two years of the rogram, the 46 atients who exercised 180 minutes or more er week also comleted the TUG an average of 4 seconds faster than the sedentary atients (<0.001, Table ). The articiants who erformed regular hysical activity engaged in a wide variety of activities (exercises rovided in the rogram handout, water aerobics, yoga, walking, weight training, swimming, stretching, tai chi chuan, bike riding, Pilates). Bodybuilders reorted less ain ( = 0.009) and erformed the TUG aroximately 4 seconds faster than sedentary atients ( = 0.01, Table 4). The addition of the results for those who swam to the body builders results maintained the difference from sedentary atients in terms of ain ( = 0.0) and TUG times (0.04, Table 5). DISCUSSION As the most common form of joint disease, osteoarthritis (OA) is associated with an extremely high economic burden. This burden is largely attributable to the effects of disability, comorbid disease, and the exense of treatment. Among a cohort of 5,15 adults aged 65 years or older with arthritis, a lack of regular vigorous hysical activity was the most revalent risk factor (64%); it almost doubled the odds of functional decline (adjusted OR 1.9, 95% confidence interval ) after controlling for all risk factors. If all subjects engaged in regular vigorous hysical activity, the exected functional decline could be reduced by as much as 2%. 8 In our series, we could not show any relation between imroved ain, function or quality of life scores and the intensity, duration or tye of hysical activity (all >0.05). This lack of association may be exlained by the relatively small number of atients who engaged in intense hysical activity () and by the fact that although many of our atients reorted that they erformed the exercises rovided in the educational booklet on a regular basis, they did not actually do all of them (several chose to erform only the stretching exercises, and those who did erform the strength exercises did not regularly increase the load). However, age emerged as a barrier to imroving inferior limb strength, function and balance, as determined by TUG erformance 16,1 ; this finding is consistent with those of Dunlo et al. 8 The atients who already racticed intense hysical activity at the time of enrollment reorted less ain than those that were sedentary (Table 2). This finding is suorted by a meta-analysis of 54 eligible trials ( harmacology, 4 exercise), including six Cochrane reviews (four harmacology, two exercise,) with 9806 articiants (2 harmacology, 419 exercise). This meta-analysis reorted a ooled effect size for harmacological ain interventions of 0.41 (95% CI: ); for exercise, the ooled effect size was 0.46 standardized mean difference (95% CI: ). This Acta Orto Bras. 1;25(1):25-9

3 Table 1. Descrition of quantitative characteristics according to imrovements in the TUG time, qualitative characteristics and statistical test results. Imroves TUG OR IC (95%) OR IC (95%) Total No Yes unadjusted Lower Uer adjusted Lower Uer Tye of hysical activity, n (%) 0,1 Sedentary 40 (85.1) (14.9) Booklet/Stretching 26 (6.5) 8 (2.5) # Walking/Fitness/Water Aerobics 51 (8.9) (.1) # Swimming/Bicycle/Bodybuilding 1 (85) (15) # Intensity of hysical activity, n (%) Sedentary 44 (88) 6 () Light 54 (8.1) 11 (16.9) # Moderate 29 (85.) 5 (14.) # Vigorous (.8) 2 (22.2) # Minutes er Week * (16.9) 101. (105.6) 1.2 (12.6) Median (min.; max.) 100 (0; 840) 0 (0; 90) 95 (0; 840) Age (years) (8.5) 64.8 (10) 6.2 (8.8) Median (min.; max.) 68 (48; 8) 65 (4; 84) 6 (4; 8) Gender, n (%) 0.4* Male 2 (91.4) (8.6) Female 10 (82.4) 22 (1.6) Race, n (%) 0.56 White 86 (8.5) 1 (16.5) Mulatto/Mestizzo 26 (81.2) 6 (18.8) Black 18 (90) 2 (10) Asian 4 (100) 0 (0) 4 # # Bilateral, n (%) 0.165* No 46 (90.2) 5 (9.8) Yes 89 (81.) (18.) BMI (5.) 2. (5.1) 1.4 (5.2) Median (min.; max.) 0. (.8;.9) 1.2 (25.9; 45.8) 0.8 (.8;.9) BFP (8.4) 9.6 (.) 8. (8.) Median (min.; max.) 40.4 (10.1;.1) 40. (18.5; 48) 40.4 (10.1;.1) Study time * (.1).9 () 8 () Median (min.; max.) 8 (1; 15) 8 (1; 15) 8 (1; 15) The total number of cases varies by variable; Interaction between the tye of activity and intensity (> 0.999); Quantitative variables: Student's t test; * Mann-Whitney test; qualitative variables: the likelihood ratio test; * Chi-square test. Table 2. Descrition of the test and scale results at baseline and after 2 years for atients who did not engage in regular hysical activity and atients who engaged in intense regular hysical activity and the results of comarative tests. Baseline 2 years n Sedentary n Vigorous activity n Sedentary n Vigorous activity WOMAC ain 8.9 (4.2) 5 (1.) (.9).4 (.4) Median (min.; max.) 9 (0 - ) 4 (4 - ) 8 (1-1) (2-15).4 (1.9) 2. (1.2) (2.1) 2.9 (2.0) Median (min.; max.) (0-8) (1 - ) (0-8) (0-6) WOMAC function limitation 1. (.4). (8.1) (14.0) 26.6 (.8) Median (min.; max.) 2 (4-6) 16 (16-0) 2 (2-65) 2.5 (2-46) 44.5 (18.2) 28. (6.4) (.1) 6.8 (1.4) Median (min.; max.) 45 (5-8) 26 (24-6) 42 (0-84) 6 (6-64) 58.1 (26.4) 2 (.5) 0.02* 59.4 (2.1) 50.9 (15.) Median (min.; max.) 60 (2-100) 25 ( - 25) 60 (5-100) 51.5 ( - 80) 11.6 (4.2) 8. (2.1) (4.9) 10. (.8) Median (min.; max.) (1.5-24) 9 (6-10). (0-21) 10.8 ( ) SF 6 - PCS 2.8 (8.2) 8.8 (4.) (9.2) 5.4 (.6) Median (min.; max.) 2.1 ( ) 21.2 ( ) 4.4 ( ).1 ( ) SF 6 - MCS 45.6 (.6) 5.0 (8.6) (1.2) 4.0 (11.8) Median (min.; max.) 44.5 ( ) 51.2 ( ) 44.5 ( ) 4. ( ) Timed U and Go. (4.0) 15.5 (11.) (11.6) 9. (2.1) 0.01* 1 2 Median (min.; max.) 11.2 ( ) 15.5 (.2-2.) 11. ( ) 9.4 ( ) 2 (8.2) 15.6 (5.) (.1) 18.6 (5.0) Median (min.; max.) 22 ( ) 15.6 ( ).8 ( ) 18.0 ( ) Baseline 2 years Acta Orto Bras. 1;25(1):25-9 2

4 Table. Descrition of the 2-year scale and test results for atients who did not engage in regular hysical activity and atients who exercised 180 minutes or more/week and the results of comarative tests. Time of hysical activity er week n Sedentary n >180 min. exercise WOMAC ain (.) 48.8 (.4) 0.28 Median (min.; max.) 8 (1-1) 2 (2-15) 60.4 (2.1) 48.4 (1.8) 0.9 Median (min.; max.) (0-8) 4 (0-6) WOMAC function limitation (14.0) 28.0 (.9) 0.5 Median (min.; max.) 2 (2-65) 0 (2-51) (18.4) (1.) 0.8 Median (min.; max.) 42 (0-84) 41 (6-0) (22.) 48.5 (21.8) 0. Median (min.; max.) 60 (5-100) 58 (0-94) 60.0 (4.9) (4.2) 0.08 Median (min.; max.). (0-21) 11 (2-18.5) SF 6 - PCS (8.9) 48 6 (8) 0.18 Median (min.; max.) 4.1 (1-5.2) 6.8 (.6-5.8) SF 6 - MCS (1.0) (11.6) 0. Median (min.; max.) 44.5 ( ) 48.8 ( ) Timed U and Go 14.6 (11.2) (.) <0.001* Median (min.; max.) 11. ( ) 9.2 ( ) 5 22 (11.8) 45.5 (8.5) 0.46 Median (min.; max.).1 ( ) 18.1 ( ) meta-analysis rovided indirect evidence that for KOA ain, the effects of exercise and those of oral analgesics are comarable. After two years, the grou that engaged in intense hysical activity erformed the TUG test faster (9.±2.1 seconds) than those who remained sedentary (14.6±11.6 seconds, =0.01, Table 2), in accordance with the exected effect of intense hysical activity described above. 8 Not all atients are able to engage in intense hysical activity (in our series, only did so; some but not all of the other atients were caable of engaging in intense hysical activity); in such cases, the weekly duration and tye of hysical activity may comensate for a decrease in intensity. Forty-six subjects engaged in regular hysical activity for 180 minutes er week or more; on average, those atients erformed the TUG test 4 seconds faster than the atients who remained sedentary (<0.001, Table ). Regular exercise for 180 minutes or more er week may become goal or a means to erforming intense hysical activity in the future among atients with KOA. The large variety of hysical activity tyes was definitely resonsible for the lack of significant correlations. The articiants who articiated in bodybuilding (weight training at the gym) and swimming, activities closely related to greater exercise intensity, reorted less ain (=0.009 and =0.04, resectively) and faster TUG erformances comared with the sedentary articiants (=0.001 and =0.0, resectively, Tables 4 and 5). Our study has limitations. It is a retrosective cohort study in which few articiants engaged in regular intense hysical activity and with considerable variety in the tyes of hysical activities that the articiants reorted. Both, diversity of hysical activity and number of articiants actually engaging intense hysical activity, diminished the ower of the test for the N and demand rosective studies for this question. Among the study s strengths, it rovides directions for future rosective randomized studies, such as carefully selecting the included age grous and restricting the tyes, duration and intensity of hysical activity. 28 Table 4. Descrition of the 2-year scale and test results for atients who did not engage in regular hysical activity and atients who swam or articiated in bodybuilding and the results of comarative tests. n Sedentary n Swimming n Sedentary n Bodybuilding WOMAC ain 8. (.9).4 (1.9) (.9) 6.4 (4.1) 0.1 Median (min.; max.) 8 (1-1) 6 (6-11) 8 (1-1) (2-15).2 (2.1).1 (1.) (2.1) 2.6 (2.2) 0.4 Median (min.; max.) (0-8) 4 (0-5) (0-8) 2.5 (0-6) WOMAC function limitation (14.0) 29.2 (5.) 1 (14.0) 2. (14.6) Median (min.; max.) 2 (2-65) 2 (22 - ) 2 (2-65) 25.5 (2-45) 42.8 (.1) 40.1 () (.1) 2.4 (.6) 0. Median (min.; max.) 42 (0-84) 6 (4 - ) 42 (0-84) 6 (6-64) 59.4 (2.1) 59.6 (16.5) (2.1) 42.6 (18.5) 0.009* Median (min.; max.) 60 (5-100) 59 (44-9) 60 (5-100) 4 ( - 5).1 (4.9) 11.6 (2.0) (4.9) 9.2 (4.5) 0.06 Median (min.; max.). (0-21) 11.5 (9-14). (0-21) 9 ( ) SF 6 - PCS 4.4 (9.2) 4.4 (6.4) (9.2).4 (8.) 0.26 Median (min.; max.) 4.4 ( ) 1.9 (28-4.) 4.4 ( ) 9.4 ( ) SF 6 - MCS 45 (1.2) 41.0 (5.8) (1.2) 51.1 (11.6) 0.1 Median (min.; max.) 44.5 ( ) 42.5 ( - 4.2) 44.5 ( ) 50.4 (2-66.8) Timed U and Go 14.6 (11.6) 11. (.1) (11.6) 9.4 (2.8) 0.01* 11 Median (min.; max.) 11. ( ) 11. ( ) 11. ( ) 9.2 ( ) 22.1 (.1) 22.1 (5.9) (.1) 1. (5.) Median (min.; max.).8 ( ) 22.9 (14.9-0).8 ( ) 15.4 ( ) Swimming Bodybuilding Acta Orto Bras. 1;25(1):25-9

5 Table 5. Descrition of the 2-year scale and test results for atients who did not engage in regular hysical activity and atients who swam or articiated in bodybuilding and the results of comarative tests. n Sedentary n Bodybuilding or swimming WOMAC ain 8. (.9) 6.9 (.5) 0. Median (min.; max.) 8 (1-1) (2-15).2 (2.1) 2.8 (2.0) 0.54 Median (min.; max.) (0-8) (0-6) WOMAC function limitation 1 (14.0) 25.5 (.2) 0.1 Median (min.; max.) 2 (2-65) 2.5 (2-45) 42.8 (.1) 5. (16.) 0.16 Median (min.; max.) 42 (0-84) 6 (6-64) 59.4 (2.1) 48.9 (.2) 0.0* Median (min.; max.) 60 (5-100) 45 ( - 9).1 (4.9) 10 (.9) 0.10 Median (min.; max.). (0-21) 11 ( ) SF 6 - PCS 4.4 (9.2) 6. (.6) 0.9 Median (min.; max.) 4.4 ( ) 8.2 ( ) SF 6 - MCS 45 (1.2) 4.4 (10.9) 0.4 Median (min.; max.) 44.5 ( ) 44.4 (2-66.8) Timed U and Go 14.6 (11.6) 10. (.1) 0.04* 18 Median (min.; max.) 11. ( ) 9.6 ( ) 22.1 (.1).4 (5.8) Median (min.; max.).8 ( ) 1. (10.5-0) CONCLUSION Patients with KOA should aim for intense hysical activity and/or more than 180 minutes of exercise er week and/or weight training (bodybuilding) for relevant ain reduction and functional imrovement. ACKNOWLEDGMENTS Our thanks to Professor Olavo Pires de Camargo, secretaries Suellen Lima and Natalia Borges, and TRB Pharma, which together with the Deartment of Orthoedics and Traumatology at the Hosital das Clínicas at FMUSP made the PARQVE roject and this retrosective study ossible. AUTHORS CONTRIBUTIONS: Each author contributed individually and made significant contributions to the develoment of this manuscrit. RAK ( X)* and FBC ( )* articiated in the study design, tabulating the data, and revising the text. FESF ( )*, CACS ( )* and CHAC ( )* articiated in the study design, led the classes, collected the atient data, and revised the manuscrit. 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