according to the osteoarthritis research society international ( oarsi ) recommendations1 , subjects with symptomatic knee 
 osteoarthritis ( oa ) might benefit from referral to a physical therapist for evaluation and 
 instruction regarding appropriate exercises for reducing pain and improving functional 
 capacity .
recently , there is increasing interest in gauging the comprehensive effects of oa 
 through evaluations of quality of life ( qol)2 , 3 .
however , it has not yet been clearly stated 
 in any clinical guidelines that exercise therapies can improve the generic health status of 
 subjects with symptomatic knee oa .
the notion that exercise therapies improve health - related 
 qol ( hrqol ) must be substantiated with high - quality evidence to support the oarsi 
 recommendations1 .
generic health status 
 instruments , such as the short form 36 ( sf-36 ) , measure multiple aspects of health , 
 including physical function , social function , and pain4 .
extensive results have been published in support of the 
 psychometric properties of the sf-365 , 6 .
the sf-36 measures the following eight 
 domains : physical functioning ( pf ) , role - physical ( rp ) , bodily pain ( bp ) , general health 
 ( gh ) , vitality ( vt ) , social functioning ( sf ) , role emotional ( re ) , and mental health 
 ( mh)4 .
the pf , rp , bp , and gh scores are 
 the strongest measures of physical health ( i.e. , these scores have the greatest weights in 
 the calculation of the physical component summary score ( pcs ) ) , and the vt , sf , re , and mh 
 scores are the strongest measures of mental health ( i.e. , they have the greatest weights in 
 the calculation of the mental component summary score ( mcs))7 . in the field of knee oa , several randomized controlled trials 
 ( rcts ) investigating the effects of exercise on improvements in hrqol , as assessed by the 
 sf-36 , have been performed . although the effects of exercise therapies on pain , muscle 
 strength , and physical function are supported by the results of meta - analysis8,9,10 , no systematic reviews with meta - analyses 
 of rcts that have investigated the effects of exercise therapy on the hrqol of subjects with 
 knee oa have yet been published .
the purpose of this systematic review was to search for 
 evidence related to improvements in hrqol due to exercise therapy in subjects with knee oa 
 as measured by the sf-36 .
studies were included in this review if they met the following criteria : ( 1 ) the 
 participants had knee oa , ( 2 ) the intervention was either exercise or exercise therapy , ( 3 ) 
 the controls were either no intervention or a psycho - educational intervention , ( 4 ) the 
 researchers assessed hrqol using the sf-36 , ( 5 ) an rct design was used , and ( 6 ) the paper 
 was written in english .
studies were excluded according to the following criteria : ( 1 ) the 
 participants had hip oa or rheumatic disease , ( 2 ) the subjects had undergone total knee 
 arthroplasty , ( 3 ) the intervention included intra - articular injections ( e.g. , sodium 
 hyaluronate ) , ( 4 ) sufficient data for the synthesis of the results were not reported , or ( 5 ) 
 the researchers used the sf-8 or sf-12 .
paper titles and abstracts were screened using the 
 inclusion and exclusion criteria . after screening , two authors read the full text of the 
 articles to determine whether or not the retrieved trials met the inclusion criteria .
the following electronic databases were searched from the earliest date available until the 
 31st of january 2014 : pubmed , the cochrane central register of controlled trials ( central ) , 
 the physiotherapy evidence database ( pedro ) , and the cumulative index to nursing and allied 
 health literature ( cinahl ) .
manual scanning of the reference lists of the included studies 
 and previous systematic reviews was also conducted to ensure that all of the relevant trials 
 were identified .
the search strategy ( table 
 1table 1.search strategy(1 ) pubmed#1 osteoarthritis , knee[mesh terms]#2 exercise[mesh terms]#3 exercise therapy[mesh terms]#4 ( # 1 and ( # 2 or # 3))limits : randomized controlled trial ( 2 ) central#1 osteoarthritis , knee[mesh
terms]#2 exercise[mesh terms]#3 exercise therapy[mesh terms]#4 ( # 1 and ( # 2 or # 3))(3 ) pedro advance searchtitle or abstract : osteoarthritis , knee , exercisemethod : clinical trial(4 ) cinahl#1 osteoarthritis , knee[mesh terms]#2 exercise[mesh terms]#3 therapeutic exercise[mesh terms]#4 ( # 1 and ( # 2 or # 3))limits : randomized controlled trial ) was a combination of free text words and medical subject headings ( mesh ) 
 terms .
all trials were independently critically appraised for methodological quality by two 
 reviewers ( r.t . and j.o . ) using the pedro scale11 .
standardized mean differences ( smds ) and 95% confidence intervals 
 ( cis ) were calculated from the post - intervention means and standard deviations ( sds ) .
if the 
 post - intervention scores were not reported , changes in the scores were used for the 
 synthesis of the results .
meta - analyses were performed with a random - effects model or a 
 fixed - effects model for outcomes that used inverse variance methods ( revman , version 5.1 ) . 

statistical heterogeneity was assessed using the i statistic ; 
 values of > 25% represent substantial levels of heterogeneity12 . to assess the risk of publication bias , funnel plots
were 
 drawn if there were 10 trials in a meta - analysis ( tests for funnel plot asymmetry only have 
 sufficient power when there are 10 trials)13 .
the grading of recommendations assessment , development and 
 evaluation ( grade ) approach14 was applied 
 to each meta - analysis performed to determine the quality of the evidence .
after removal of the duplicates , the 
 titles and abstracts of 438 studies were screened .
full - text copies of 17 trials were 
 retrieved for closer examination . of these ,
five were excluded , and consensus was reached on 
 including a total of 12 trials in the review ( fig . 

the 12 trials involved 1,239 participants . the available data for the exercise groups 
 indicated that the mean ages and female ratios across all studies ranged from 54.8 to 70.2% 
 and 50 to 100% , respectively ( table 2table 2.summary of included trials ( participants characteristics and 
 intervention)studyparticipants ( exercise group)participants ( control group)exercise interventionfrequency ( per week)duration ( weeks ) pedro scoreaglamis et al .
2009n = 16age ( yrs ) = 56.8 ( 4)female ( % ) = 100n = 9age ( yrs ) = 54.4 ( 12)female ( % ) = 100aerobic , functional strengthening , and flexibility 
 exercises3123an et al .
2008n = 14age ( yrs ) = 65.4 ( 8.2)female ( % ) = 100n = 14age ( yrs ) = 64.6 ( 6.7)female ( % ) = 100baduanjin584baker et al .
2001n = 23age = 69 ( 6)female ( % ) = 73.9n = 23age = 68 ( 6)female ( % ) = 82.6two functional exercises ( squats and step - ups)3167brosseau et al .
2012n = 79age = 63.9 ( 10.3)female ( % ) = 69.9n = 74age = 62.3 ( 6.8)female ( % ) = 63.5walking3484doi et al .
2008n = 71age ( yrs ) = 66.8 ( 12.8)female ( % ) = 77.5n = 70age ( yrs ) = 68.9 ( 21.1)female ( % ) = 74.6quadriceps strengthening exercises786fransen et al .
2001group 1n = 43age ( yrs ) = 68.5 ( 8.7)female ( % ) = 74group 2n = 40 age ( yrs ) = 65.3 ( 7.1)female ( % ) = 78n = 43age ( yrs ) = 66.1 ( 10.3)female ( % ) = 67group 1 : the choice , frequency , and duration of 
 individual treatments at the discretion of the treating physical therapistgroup 
 2 : quadriceps muscle strengthening exercise , stretching , aerobic exercise , and 
 patella taping287lee et al .
2009n = 29age ( yrs ) = 70.2 ( 4.8)female ( % ) = 93n = 15age ( yrs ) = 66.9 ( 6.0)female ( % ) =
2010group 1n = 26age ( yrs ) = 65.7 ( 8.9)female ( % ) = 88.5group 2n = 25age ( yrs ) = 67.7 ( 7.7)female ( % ) = 84n = 24age ( yrs ) = 63.3 ( 5.3)female ( % ) = 87.5group 1 : aquatic exercise ( in water , forward , 
 backward , and side walking ; underwater bicycling ; strength training ; fast walking 
 with swinging arms ; and aqua running)group 2 : land - based exercise ( joint 
 mobilization ; strengthening exercises , range - of - motion exercise ; stretching 
 exercises ; and bicycling)387oreilly et al .
1999n = 78age = 61.9 ( 10.0)n = 113age = 62.2 ( 9.7)isometric quadriceps contraction , isotonic quadriceps 
 contraction , isotonic hamstring contraction , and dynamic stepping exercise7247rejeski et al .
2n = 68age = 68.5 ( 5.6)female ( % ) = 73.3n = 68age = 68.6 ( 6.3)female ( % ) = 66.7group 1 : exercise only ( aerobic phase , 
 resistance - training phase , second aerobic phase , cool - down phase)group 2 : 
 exercise + diet3726salli et al .
2010group 1n = 25age ( yrs ) = 55.7 ( 8.2)female ( % ) = 
 82.6group 2n = 25age ( yrs ) = 57.1 ( 6.8)female ( % ) = 83.3n = 25age ( yrs ) = 58.3 ( 6.7)female ( % ) = 79.2group 1 : combined concentric - eccentric exercisegroup 
 2 : isometric exercise ( progressive)386thorstensson et al .
2005n = 30age ( yrs ) = 54.8 ( 7.1)female ( % ) = 50n = 31age ( yrs ) = 57.3 ( 4.7)female ( % ) = 50weight - bearing exercises , endurance , and lower limb 
 strength266 ) .
the trials included in our study used muscle strengthening exercises with or 
 without weight bearing , walking , balance exercises , muscle stretching exercises , tai chi 
 exercises , baduanjin , or functional exercises .
the sf-36 versions that were used were in 
 english , turkish , japanese , and korean ( table 
 3table 3.summary of included trials ( instrumental information)studythe sf-36versioncalculated scalepooled scorein our meta - analysissignificantly deferencebetween groups in 
 baselineaglamis et al .
2009turkish eight scaleschange scorespf , bp , gh , vt , and mhan et al .
2005englishpcs and mcschange scoresnonepf : physical functioning , bp : bodily pain , gh : general health , vt : vitality , sf : 
 social functioning , mh : mental health ) .
pf : physical functioning , bp : bodily pain , gh : general health , vt : vitality , sf : 
 social functioning , mh : mental health the results of the individual studies and synthesis of the results are shown in table 4table 4.meta-analysis of the effect of exercise therapy on hrqol ( sf-36)no . of trials(exercise groups)ratio of trials(pedro < 6)no .
[ 95% ci]iquality of theevidence ( grade)summary2 ( 2)0%1650.47 [ 0.16 , 0.78]0%highphysical component summary7 ( 10)14%7710.52 [ 0.21 , 0.83]76%moderatemental component summary7 ( 10)14%7710.44 [ 0.12 , 0.75]77%moderatephysical functioning4 ( 5)25%5870.28 [ 0.12 , 0.45]0%highrole physical4 ( 5)25%5870.26 [ 0.10 , 0.43]19%highbodily pain4 ( 5)25%5870.22 [ 0.04 , 0.47]55%moderategeneral health5 ( 6)40%6080.15 [ 0.01 , 0.31]6%highvitality4 ( 5)25%5870.09 [ 0.07 , 0.26]0%highsocial functioning5 ( 6)40%6080.17 [ 0.08 , 0.43]54%moderaterole emotional 4 ( 5)25%5870.07 [ 0.10 , 0.23]0%highmental health5 ( 6)40%6080.15 [ 0.08 , 0.37]41%moderate reason for downgrade : statistical heterogeneity ( i 
 > 25% ) . among the 12 trials15,16,17,18,19,20,21,22,23,24,25,26 included in our study , the data of aglamis 
 et al.16 were not included in the 
 synthesis of the results for physical function , body pain , mental health , vitality , or 
 general health , because their scores at baseline were already significantly higher in the 
 exercise group than in the control group . the results of our meta - analysis provided 
 high - quality evidence that exercise therapy increased the summary score , pf score and rp 
 scores of knee oa sufferers .
our meta - analysis also provided moderate - quality evidence that 
 the physical component summary and mental component summary scores were improved to a 
 greater extent by exercise therapy than by control interventions .
using disease - specific instruments , previous systematic reviews have confirmed the effects 
 of exercise therapy on pain and physical function of subjects with knee oa27 . the western ontario mcmasters university 
 arthritis index ( womac ) comprises three subscales that evaluate pain , physical function , and 
 stiffness , and positive changes in womac scores reflect improvements in these problems .
our 
 data show that the score of not only the womac but also the sf-36 , which is not a 
 disease - specific instrument , were improved by exercise therapy .
the reason for these 
 findings might be that , like the womac , the sf-36 includes domains concerned with physical 
 function .
the scores for not only the pf but also rp increased to greater degrees in the 
 exercise groups than in the control groups , and this evidence was judged to be of high 
 quality . our results confirmed that exercise therapy is mildly to moderately effective at 
 improving the generic health status of subjects with knee oa in terms of the physical 
 components . regarding the development of practice guidelines , these findings will be useful 
 for the recommendation of exercise therapy for improving hrqol .
our results also show that the mcs scores were significantly higher in the exercise therapy 
 groups than in the controls .
the mcs score were significantly higher in the intervention 
 groups , but the scores on the mh , re , sf , and vt scales ( particularly the vt and re scales ) 
 were not different .
there were differences among the studies regarding the choice of the 
 outcome measures , mcs , mh , re , vt , and sf , and these differences affected our findings . in 
 three21,22,23 of the four studies in 
 which only the mcs was reported , the standard mean difference in the mcs was moderate to 
 very high . although scale - level data were not available for these three studies , it is 
 likely that both the vt and re improved because the mcss substantially improved .
conversely , 
 in the two studies24 , 26 which reported both vt , re and mcs data , none of the scales 
 improved much . in the former three studies , the exercise intervention durations were 8 
 weeks .
in contrast , the exercise intervention durations were 48 to 72 weeks in the latter 
 studies , which represented a more than 6-fold increase compared to the former three studies . 

the efficacies of exercise improving hrqol , especially with regard to physical component of 
 subjects with knee oa , are supported by the results of our meta - analysis .
the results of our 
 present study suggest that clinicians should make use of the strong evidence to choose 
 exercise therapies to improve hrqol of subjects with knee oa .
evidence regarding the effect of exercise therapy has not previously been based on generic 
 health status instruments27,28,29 . however , sf-36 
 is a generic health status instrument4 . 
 although some of the studies used translations of the sf-36 ( turkish , japanese , and korean ) , 
 these versions have been tested for their validity and reliability30,31,32 .
it is important to confirm that exercise therapy can 
 effectively improve global hrqol , including mental health , rather than only influencing 
 disease - specific domains .
our study s second strength was that the quantitative effect of 
 exercise on hrqol was clarified by performing a meta - analysis .
thus , comparisons of the 
 effects of exercise therapy with the effects of other interventions on hrqol scores became 
 possible .
the exercise intensities , session durations , and numbers of sets were not always 
 similar among the trials .
although the smd was used as the summary measure , high statistical 
 heterogeneity was observed in both the pcs and mcs .
because the reasons for these high 
 heterogeneities could not be determined , the effect size should only be used as a reference . 

future meta - analyses of rcts with similar exercise protocols should be performed to decrease 
 the variance of the effects at the study level .
the second limitation was publication bias . 
 according to the cochrane handbook for systematic reviews of interventions33 , tests for funnel plot asymmetry , which 
 indicates the presence of publication bias ,
should only be performed when at least 10 
 studies have been included in the meta - analysis because fewer studies result in a test power 
 that is too low to distinguish chance from real asymmetry .
the presence of publication bias 
 could not be determined , because the number of studies included in our meta - analysis was too 
 small to perform this test . if publication bias were recognized and eliminated in future 
 systematic reviews using egger s test , it is probable that the pooled effect size for hrqol 
 would be smaller than that observed in present data .
another limitation was trials that used 
 the sf-36 were collected to confirm the effect of exercise therapy on hrqol , and trials that 
 used other instruments were excluded .
a comparison of the orthopaedic literature from 1991 
 with that from 2001 suggested that the tool most commonly used to determine the patients 
 perspectives was the sf-3634 . 

additionally , a systematic review performed by veenhof et al . suggested that the most 
 appropriate questionnaires for patients with hip and/or knee oa seem to be the 
 condition - specific questionnaire womac and the generic questionnaire sf-3635 .
therefore , this limitation probably did 
 not affect our results to a measurable degree . in conclusion
, this systematic review demonstrated that exercise therapy can improve hrqol , 
 as assessed by the sf-36 , of knee oa sufferers .
however , this review failed to clarify 
 whether the effect sizes of exercise therapies on hrqol , particularly the pcs and mcs , are 
 influenced by dissimilar protocol designs among trials or by publication bias .
 [ purpose ] the aim of this study was to examine the effects of exercise therapy on the 
 health - related qol of people with knee osteoarthritis . [ subjects ] four databases ( pubmed , 
 cochrane central register of controlled trials , the physiotherapy evidence database , and 
 the cumulative index to nursing and allied health literature ) were searched for randomized 
 controlled trials that evaluated the effects of exercise therapy on health - related qol 
 assessed by the sf-36 for inclusion in our systematic review . 
 the methodological qualities 
 of the trials were assessed independently by two reviewers using the pedro scale . pooled 
 
 analyses with a random - effects model or a fixed - effects model were used in the 
 meta - analyses to calculate the standardized mean differences and 95% confidence intervals . 
 [ results ] 
 twelve studies met the inclusion criteria . 
 our meta - analysis provides 
 high - quality evidence that exercise therapy increases the summary score , physical 
 functioning score , and role - physical score of knee osteoarthritis sufferers . 
 our 
 meta - analysis also provides moderate - quality evidence that the physical component summary 
 and mental component summary scores were improved to a greater extent by exercise therapy 
 than by control interventions . 
 [ conclusion ] exercise therapy can improve health - related 
 qol , as assessed by the sf-36 , of knee osteoarthritis sufferers . 
INTRODUCTION
SUBJECTS AND METHODS
RESULTS
DISCUSSION