Muscle Dysfunction and Effective Rehabilitation of Knee Osteoarthritis: What We Know and What We Need To Find Out

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1 Arthritis & Rheumatism (Arthritis Care & Research) Vol. 49, No. 3, June 15, 2003, pp DOI /art , American College of Rheumatology SPECIAL ARTICLE Muscle Dysfunction and Effective Rehabilitation of Knee Osteoarthritis: What We Know and What We Need To Find Out MICHAEL V. HURLEY Introduction Osteoarthritis (OA) is a ubiquitous condition that frequently affects the knee joint and can cause severe pain and disability (1,2). Although pain is the cardinal symptom of knee OA, patients frequently report muscle weakness and fatigue. This article reviews what we know about the involvement of muscle dysfunction in knee OA, the effect muscle dysfunction has on the development and course of OA, whether exercise addresses muscle dysfunction and benefits patients, what the most effective and efficient exercise regimens are, and what the best way is to deliver these to the large patient population with knee OA. This is not an exhaustive, systematic review and no attempt has been made to assess and rate the quality of the cited studies. The clinical importance of muscle in knee OA Research into the cause, consequences, and management of OA has focused on the pathologic changes in the articular cartilage and bone. Changes in periarticular muscles and the nerves controlling them have received much less research attention, even though neuromuscular dysfunction can have serious consequences on articular function and health. Muscles have extremely important motor functions; they effect movement, bestow stability, protect against abnormal movement, and dissipate harmful forces generated during gait. In addition, muscles have a vital Dr. Hurley s work is supported by the Arthritis Research Campaign. Presented at the International Conference on Health Promotion and Disability Prevention for Individuals and Populations With Rheumatic Disease: Evidence for Exercise and Physical Activity, St. Louis, MO, September Michael V. Hurley, PhD, MCSP: King s College, London, United Kingdom. Address correspondence to Michael V. Hurley, PhD, MCSP, Rehabilitation Research Unit, King s Healthcare (Dulwich), East Dulwich Grove, Dulwich, London, SE 22 8PT, UK. Mike.Hurley@kcl.ac.uk. Submitted for publication June 20, 2002; accepted in revised form November 2, sensory function contributing to the appreciation and control of body position sense and movement. To function optimally, a muscle needs to be strong, uninjured, nonfatigued, under accurate motor control, and have an intact sensory mechanism. Deconditioned or damaged muscles and their innervating nerves cause motor (e.g., weakness) and sensory (e.g., decreased proprioceptive acuity) dysfunction. Numerous studies have demonstrated that quadriceps weakness occurs early in OA (3 9), and is a more important determinant of pain and disability than radiologic changes to bone and cartilage (9 16). Muscle dysfunction in the pathogenesis of knee OA It usually is assumed that joint damage causes pain and restricts mobility, resulting in muscle weakness, but muscle dysfunction may have an unappreciated involvement in the pathogenesis of OA (17). An epidemiologic study of joint damage and pain in a community population concluded that quadriceps weakness might precede radiologic joint damage and pain (9). This could be explained if muscle sensorimotor dysfunction due to aging (18 22), fatigue (5,23,24), delayed reaction time (25), previous minor trauma (19,21,26 28), or abnormal articular sensory input (6,29,30) impaired neuromuscular protective reflexes and shock absorption capacity causing excessive, rapid, jarring joint loading during gait. This leads to microtrauma and attrition of articular cartilage, and microfractures and sclerosis of subchrondral bone the radiologic features of knee OA (25,31,32). Efficacy of exercise in the management of knee OA Appreciating the involvement of muscle in OA is important because muscle is a physiologically plastic tissue that can be exercised to improve strength, endurance, and skill, even in very elderly people. Therefore, rehabilitation regimens that address muscle dysfunction might prevent or alleviate some of the problems associated with OA. Evidence is now accruing (33) that demonstrates the benefit of exercise in the management of patients with knee OA (Table 1). Rehabilitation programs have shown 444

2 Strengthening Exercises in Knee Osteoarthritis 445 Table 1. Summary of studies investigating the efficacy of exercises for patients with knee OA* Author, date (reference) Sample size; type, frequency, and duration of exercise and control interventions; environment of intervention; followup period Outcome measures and findings Comments Fisher et al, 1993 (5) 40 subjects nonrandomly allocated; Individualized program to increase active and passive ROM, strength, pain, function, and patient education, 3 1-hour sessions per week for 12 weeks; clinic based; no control group Fransen et al, 2001 (36) Messier et al, 2000 (40) Maurer et al, 1999 (39) Rogind et al, 1998 (42) Hopman-Rock and Westhoff, 2000 (37) Chamberlain et al, 1982 (34) O Reilly et al, 1999 (41) 126 patients randomized; Individual or group exercise (6 patients per group) all had patient education of benefits of exercise followed by progressive regimen of stretches and strengthening exercises; Some electrotherapy treatments, 2 1-hour exercise sessions per week for 8 weeks; Clinic based with home exercise regime 3 days a week; Wait-list control who were later randomized to individual or group rehab; Followup: 2 months 24 patients randomized; Strengthening and walking exercise regimen, combined with dietary control involving healthy eating advice and problem solving techniques; control: Exercise regimen only 3 1-hour exercise sessions per week for 24 weeks; clinic based 113 patients randomized; Strength training regimen minute exercise sessions each week for 8 weeks; control: 4 lectures and discussions with pamphlets on education and self management; clinic based; followup: 8 and 12 weeks from baseline 25 patients randomized: Progressive regimen of stretches, strengthening, balance, and coordination and general fitness exercises, 2 1-hour sessions a week for 12 weeks in groups of 6 patients; clinic based with home exercise regimen performed on 4 other days; control: Ambiguously reported but appears to have had no exercise; followup: 1 year postrehabilitation 120 patients randomized; 1 2-hour session each week for 6 weeks of patient education, self management advice, and exercises to increase strength, balance, and function; control: received no treatment; clinic based; followup: 6 months 42 patients unequally randomized; progressive exercise regimen practiced on 3 occasions; control: application of short wave diathermy and 2 exercises to increase strength and endurance were carried out 3 times per week for 4 weeks; clinic based and at home; after 4 weeks patients were recalled, reassessed and told to continue exercise with improvised equipment at home; irrespective of their initial allocation some patients were told they would be recalled after 12 weeks others were not; all patients recalled and reassessed at 12 weeks 191 patients received initial general advice then randomized; Underwent progressive home-based exercise program of strengthening and stepping exercises, performed daily and were subsequently visited at 2, 6, and 12 weeks; control: no intervention Muscle strength and endurance: increased; Jette Functional Status Index: improved; patient assessment of pain and function: improved; Improvements came within 1 month, but additional ones after this time; No exacerbation of condition WOMAC: pain and function subscales improved; SF-36: improved; gait analysis: improvement in some parameters; muscle strength: increased; No difference whether rehab performed in groups or on individual patients; Improvements maintained for 2 months postrehab Gait analysis: some parameters improved; muscle strength: improved in exercise only group; physical function: improved; pain: improved; biochemical markers of cartilage degradation: unchanged; body mass: dietary group lost weight (15 lbs more than exercise alone) Muscle strength: increased; pain: decreased; function (AIMS2, WOMAC, SF-36): some improvements Muscle strength: improved; algofunctional index: improved; pain: decreased, particularly night pain; walking speed: increased; clinical findings: increase in the number of knee effusion in the intervention group; postural sway: unchanged; Improvements in some subjective measures not observed until 12 month followup Pain: less frequent in the intervention group; patient self-assessed quality of life: unchanged in the intervention group, but declined in the control group; muscle strength: unchanged; observed activity restrictions: unchanged; knowledge and self efficacy: improved; BMI: decreased; healthcare utilization: use of medication similar, but less patients in the intervention group saw physiotherapists Muscle strength: increased; endurance: improved; flexibility: unchanged; function: improved; pain: decreased; improvements seen irrespective of whether the exercises were performed in clinic or at home; patient who didn t know they were going to be recalled after 12 weeks did worse than those who knew they would be recalled Pain VAS and WOMAC: decreased; quadriceps strength: increased; quadriceps activation: some improvements; SF-36: some improvement; anxiety and depression: some improvement; body mass: unchanged; medication use: slight reduction Later small study (reference 6) showed shorter exercise regimen completed in 8 weeks had similar results 24 therapists delivered the intervention increasing the generalizability of the findings Obese, community dwelling population; disease activity not exacerbated by exercising Education program was considered less costly though exact costs are not reported Delayed improvements may be related to delayed enhancement of general feeling of well-being Mixture of hip and knee patients investigated. More proactive followup interventions, e.g., telephone contact, encouraged Authors concluded that patients need equipment lending library, a few simple exercises reinforced with verbal and written information, and regular followup to maximize the efficacy of home exercises Simple low cost package home exercise regimen improved physiological and psychological parameters

3 446 Hurley Table 1. Continued Author, date (reference) Sample size; type, frequency, and duration of exercise and control interventions; environment of intervention; followup period Outcome measures and findings Comments Hurley and Scott, 1998 (53) 89 patients nonrandomly allocated; progressive strengthening, balance, coordination, and functional exercise regimen, 2 30-minute exercise sessions each week for 5 weeks; control: wait-list control group who had no intervention, but later offered rehab; clinic based; followup: limited followup at 6 months Minor et al, 1989 (49) 120 patients randomized; Aerobic walking group who had progressive regimen of strengthening, flexibility, stretching exercises that included minutes of walking on level course, Aerobic water exercises that involved jogging in shallow and deep water modified calisthenics; control: gentle active ROM, isometric strengthening and relaxation exercises, no aerobic exercises, 3 1-hour sessions each week for 12 weeks; clinic based; followup: 9 months postrehabilitation Deyle et al, 2000 (45) 83 patients randomized; progressive exercise regimen of Patrick et al, 2001 (50) Ettinger et al, 1997 (46) strengthening, ROM, and stretching exercises (30 45 minutes) with electrotherapy modalities with manual therapy if considered appropriate by the therapist (30 minutes), performed twice a week for 4 weeks; clinic based with home exercises on days when not attending clinic; control: subtherapeutic ultrasound (10 minutes); followup: 51 patients followedup 1 year after rehabilitation 249 patients randomized; aquatic exercise regimen to increase strength, flexibility, and ROM; clinic based in classes of 6 40 persons (mean of 16), minute classes a week for 20 weeks; control: patients told to continue usual pattern of activity and not begin new exercises 439 patients randomized; 1) Aerobic program of exercises including 40 minutes walking; clinic based, groups of patients, 3 1-hour sessions each week for 3 months, followed by 15-month home-based walking program with telephone support. 2) progressive strengthening exercise program; clinic based in groups of patients, 3 1-hour exercise sessions per week for 3 months, followed by 15-month home exercise program with telephone support; control: health education program comprising hour education sessions, clinic based with groups of patients during first 3 months, followed by 15-month telephone support Kovar et al, 1992 (48) 102 patients randomized; stretching and strengthening exercise regimen with focus on walking program, supplemented with education program incorporating behavioral psychological elements; clinic based, minutes sessions per week for 8 weeks; control: routine treatment for 8 weeks with weekly telephone contact; followup: Later report (Sullivan et al, 1998 [59]) followed cohort at 1 year Quadriceps strength: increased; voluntary activation: increased; proprioceptive acuity: increased; objective functional performance: improved; Lesquesne Index: improved; improvements maintained for 6 months Exercise tolerance: increased in both aerobic exercise groups; flexibility: improved in all groups; AIMS: some improvements in aerobic groups; Tennessee Self-Concept Scale: some improvements in aerobic groups; self reported exercise behavior: some improvements in aerobic groups WOMAC: improved; 6-minute walk test: distance increased; improvements were evident after 1 year but the data was not presented Adherence with intervention very poor and costs of treatment very high, only 30% of patients attended a minimum of 2 classes per week for 16 weeks; for patients who adhered to treatment: Quality of Well-Being: improved; Current Health Desirability Rating; HAQ: improved; Center for Epidemiological Studies Depression Scale: unchanged; perceived quality of life: unchanged; economic estimation of quality adjusted life years: no difference; there was no difference between control group and nonadherers Self-report of physical disability: improved in both intervention groups; objective measure of physical performance: improved in both intervention groups; exercise tolerance: improved in both intervention groups; muscle strength: unchanged; x-rays: unchanged; knee pain: improved in both intervention groups; 70% of patients compliant with regimen; both exercise groups showed a dose-related response between compliance and effects on outcomes: patients who complied best had largest improvements 6-minute walking test: increased; AIMS: subscales for pain and physical activity improved, with lesser improvements in impact of arthritis and medication use subscales Sensory aspects of muscle function affected by OA can be addressed during relatively brief, rehab regimen that involved simple exercise Mix of OA and RA patients and of hip, knee, and tarsal joint involvement After 1 year more patients in the control group accepted arthroplasty than in the intervention group, but study underpowered to properly assess this finding Site and diagnosis of OA not documented; the use of HAQ is an inappropriate outcome measure as it is insensitive for patients with lower limb OA, and the authors suggest other outcome may also be insensitive; the cost of long-term hydrotherapy very high and cannot be justified The exercise regimens gave improvements in spite of not being intensive and the control group having the benefits of an intervention that would be expected to increase their health status and compliance with lifestyle changes likely to improve their condition; long-term adherence with moderate exercise regimen does not worsen the condition Combination of simple exercise and walking effective and supplementation with behavioral psychosocial interventions improved exercise adherence; however, another report of 1 year followup suggested benefits and exercise adherence not maintained

4 Strengthening Exercises in Knee Osteoarthritis 447 Table 1. Continued Author, date (reference) Sample size; type, frequency, and duration of exercise and control interventions; environment of intervention; followup period Outcome measures and findings Comments Petrella and Bartha, 2000 (51) Bautch et al, 1997 (44) Van Baar et al, 1998 (52) Halbert et al, 2001 (58) Thomas et al, 2002 (61) 179 patients received antiinflammatory agents then randomized; progressive program of flexibility and strengthening exercises; 8-week home based program beginning with 10 minutes of exercises performed 3 times for first 2 weeks progressing to 45 minutes of exercises performed 5 days a week in week 7; Control: nonprogressive exercise regimen of nonweight-bearing ROM exercises without resistance, home based for 8 weeks; No followup 34 patients received educational program and clinicbased progressive regimen of strengthening and flexibility exercises and individualized walking regimen at self selected speed then randomized; Half randomized to receive frequent treatment, i.e., 3 1-hour exercise sessions per week for 12 weeks; Control: half patients had minimal treatment, i.e., 1 1-hour exercise session per week for 12 weeks 201 patients randomized; patient education and medication from GP with exercise regimen to increase strength, mobility, and coordination; the content, intensity and frequency of the regimen was tailored by the physiotherapists to address individual patient s needs; each week minute exercise sessions were performed for a maximum of 12 weeks; primary care clinic based; patients were discharged when the treatment goals had been achieved with advice and encouragement to continue exercises at home; control: patient education and medication from their GP only, no exercises; followup: 9 months after end of intervention (Van Baar et al, 2001 [60]) 69 patients randomized; individualized physical activity advice to exercise aerobically 3 20-minute sessions a week; seen at baseline, 3, and 6 months later to discuss progress; remained under GP care; control: patients received pamphlet that was explained to them and discussed with them 3 and 6 months later; Primary care clinic and home based; Followup: 12 months 786 community based respondents to postal survey enquiring about knee pain; complex methodology but essentially (graded elastic bands used as knee extensor resistance for minutes daily (maximum of 20 contractions); assessed at 6 monthly intervals with monthly telephone contact between assessments and self completed diary to encourage and monitor adherence; control: patients received no contact between assessments; home based; followup: 6, 12, 18, and 24 months Pain and function using objective measures and WOMAC: improved; Physical Activity Scale in the Elderly: improved Synovial keratin sulfate and hydroxyproline assessed cartilage degradation (in 11 patients only): unaltered by the level of exercise intensity; x-rays: no change in radiographic features; pain during past week and at assessment: minimal exercise group had no change in pain; frequent exercise group had decreased pain; AIMS: minimal exercise group had improved AIMS score, frequent exercise group had no change Pain in the past week: improved; medication use: unchanged; observed disability: improved; self reported disability (Influence of Rheumatic Disease on General Healthy and Lifestyle): improved; muscle strength: unchanged; flexibility: some improvement; Fear-Avoidance Beliefs Questionnaire: unchanged; amount of physical activity in past week: unchanged Physical activity: increased walking frequency and duration; intention to exercise: intervention patients tended to increase their intention to exercise whereas control patients tended to regress in their intention to exercise; OA symptoms (pain, stiffness function): unchanged but for small decrease in function of control patients; SF-36: unchanged WOMAC: pain subscale was primary outcome measure which decreased in exercise groups at all assessments; WOMAC: stiffness and function subscales secondary outcomes reduced in exercise group at 24 months; isometric strength: in selected sub group had increased; SF-36: no change following exercise; hospital anxiety and depression scale: no change following exercise Fewer patients progressed from the 6 8 week stage than progressed from the 1 4 week stage, it is suggested patients may have a ceiling to the amount and intensity of exercise they will tolerate, or less patients perceive the need to exercise beyond the stage reached by week 4 Small sample size for assessment of markers of cartilage degradation is problematic, but the invasive nature of the assessment will limit the number of patients this can be performed on. Evidence here suggests there is no adverse effect due to intensive exercise Patients with hip and knee OA included but results suggested no difference in the effectiveness with regard to the site of OA; being performed in the primary care setting with several different GPs (n 43) and physiotherapists (n 39), and performed under type of conditions usually experienced in clinical practice and tailored to the needs of the patients reflects normal clinical practice thereby enhancing the generalisability of the findings; nine months after the end of rehabilitation the benefits gained had been lost Patients require little incentive to begin considering and implementing changes in their physical activities Relatively simple home-based intervention had reasonable effect on pain and other secondary outcomes; in spite of telephone contact and regular assessment, adherence to regimen was moderate, but reduction in pain was dose-related: those who adhered to exercise had biggest reduction pain; moderate adherence may be due to burden of doing formal daily exercises in population not seeking medical attention for their knee problem * ROM range of motion; WOMAC Western Ontario McMaster Osteoarthritis Index; SF-36 Short Form 36; AIMS2 Arthritis Impact Measurement Scales 2; BMI body mass index; VAS visual analog scale; OA osteoarthritis; RA rheumatoid arthritis; HAQ Health Assessment Questionnaire; GP general practitioner.

5 448 Hurley exercise can increase muscle strength (3 6,34 42). Many different regimens, involving static and dynamic contractions, weights, and manual and other forms of resistance, have been employed to effect these improvements. However, the underlying physiologic principle is that the stimulus required to effect strength increase involves performing a low number of maximal (or near maximal) contractions (43). However, strength increases are of little value to patients if this does not reduce pain and disability. Fortunately, these studies show strength increase is associated with reduced pain and disability, without exacerbating knee damage (3 5,34 42,44 52). In addition, incorporating into rehabilitation regimens exercises that hone neuromuscular protective reflexes by improving reaction time, balance, and coordination will improve functional joint stability and proprioception (53), restore shock absorption capacity, and protect against further joint damage (54 56). Development of clinically effective rehabilitation regimens Unfortunately, most of these studies (5,38 40,42,44 46, 49,50) demonstrate the efficacy of research regimens (i.e., their ability to increase strength under ideal research conditions), employing complex, prolonged, labor-intensive, and expensive exercise regimens. Almost invariably such regimens are less efficacious when implemented in clinics where external constraints (e.g., facilities, time, manpower, and financial) impair clinicians ability to provide idealized health care regimens (57). Therefore, efficacious research regimens must be adapted to make them clinically effective (i.e., work under routine clinical conditions). A brief, simple exercise regimen improved quadriceps strength, proprioceptive acuity, and disability (53), but it involved individual patient treatment making it labor intensive and expensive. Further development is required to make these regimens more clinically effective, practical, and affordable. Facilitating habitual exercise in the community In general, rehabilitation of patients with knee OA involves participation in brief, hospital-based, supervised exercise regimens, supplemented with information about the condition and self management strategies, then discharge with advice to continue exercising at home. Followup appointments to check adherence with exercises and reinforce their importance is rare, so adherence with home exercise decreases over time. Consequently, exercise has been criticized as benefiting only while people are exercising; when they stop exercising the benefits can be maintained for a short time (36 38,42,45,49,58) but the gains are likely to be lost over time (59,60) unless patients are actively encouraged to continue exercising (34,37, 41,46,61). These criticisms should not detract from the value of exercise, but should stimulate investigations into how to encourage regular participation in exercise, thereby maintaining the benefits. In addition, most of the efficacious research regimens were largely hospital based (44) (5,34,36 40,42,45,46,48 50) but the prevalence and chronicity of knee OA make prolonged hospital management financially or logistically impractical. Home and community-based exercise regimens can increase muscle strength and improve function (34,41,51,52,58,61). Exercise regimens that are complex, lengthy, strenuous, necessitate the use of sophisticated equipment, cost extra, and require help are too difficult for elderly people to implement. To maximize adherence, exercise regimens must be simple and practical, but even adherence with simple exercise regimens wanes over time. Regular exercise can be facilitated by explaining the aims of management (62,63), enhancing patients self efficacy for exercise (their confidence in their ability to exercise) (64 67), and regularly reinforcing the benefits of exercise (68 72). Unfortunately, fewer than half of patients with OA recall being advised to exercise (73) because the advice was never given, or lacked conviction, or was impractical, or people forget, or selectively hear and recall what is discussed during medical consultations. To be effective, exercise advice given to patients must be beneficial, practical, and given with conviction by healthcare professionals. Reinforcement of this advice need not be complex or expensive: regular telephone followups are likely to be an effective and cheap way of improving exercise compliance (74,75). Other strategies (such as frequent personal or telephone contact with health care professionals, integrating exercise into social events, etc.) designed to improve longterm physical activity of elderly people in the community with other medical conditions (69 71,76,77) could be adopted for patients with knee OA (34,37,41,46,61). Moreover, initiatives to improve people s health, through regular participation in moderate physical activity (78,79), might be reinforced by highlighting the association between physical activity and articular health. The challenge in the management of knee OA is to establish clinically effective exercise regimens and find ways to maintain these benefits by encouraging and enabling patients to participate in regular exercise. Ultimately, our understanding of why patients do or do not participate in habitual physical activity will only be gleaned from patients themselves, employing qualitative research methodologies to establish the reasoning behind patient s decisions (80 82). Implications for making physical activity or exercise recommendations Adequate rehabilitation of patients with knee OA must include a variety of exercises to address motor and sensory deficits, and practice skills required to meet challenges of daily life. Rehabilitation should comprise a simple, practical, progressive exercise regimen, individually adapted to meet the needs of each patient and revised as necessary to continually challenge patients to work as hard as possible (53). It should include exercises to increase strength, effected by performing as few as about 10 per day of maximum, or near maximum, voluntary contractions against a high resistance; endurance, numerous, daily, submaximal contractions against a low resistance, cycling, walking; control of movement, using elastic therapeutic bands; balance and coordination, to improve confidence, standing with eyes shut, standing on 1 leg with eyes open

6 Strengthening Exercises in Knee Osteoarthritis 449 and shut, use of unstable wobble boards, etc. Most importantly, these improvements need to be converted into improved functional performance by practicing common activities of daily living: from sitting in a chair to standing, step on/off a block or bottom step, walking, etc. Initially, exercise may need to be performed under supervision to maximize patient understanding, compliance, and confidence, and so they can receive reassurance that exercise does not cause or exacerbate joint damage and so the benefits of regular physical activity can be reinforced. This physical activity need not be formal exercising; walking, gardening, dancing, and swimming are all excellent forms of physical activity. Nor does it have to be strenuous; 30 minutes of mild to moderate physical activity (a brisk walk) performed daily or on most days of the week are beneficial, and this 30 minutes can be accumulated, i.e., in 3 brisk 10-minute walks (78,79). When discussing exercise with patients, several points should be emphasized. Most importantly, it needs to be made clear exercise will not cure OA; they will continue to experience episodes of pain (though hopefully less frequent and less intense pain). They must learn to intersperse rest and activity to avoid over stressing painful, weak, vulnerable joints. If they are having a bad day or week, they should rest not take to their beds, just ease back on their activities and exercise until the pain has subsided. However, once the pain has subsided the patient must understand the importance of resuming their activity slowly, gently, and progressively. Although exercise may cause some discomfort (e.g., muscle ache) this should not be excessive or last for more than a day or two. To minimize this discomfort, patients should begin exercise gently and progress slowly as they feel stronger and fitter. In addition, patients must understand that participation in regular exercise and physical activity gives them a coping strategy that they can implement to gain some control over their symptoms and self manage their condition. Suggestions for future research Exercise in primary prevention of knee OA. It may be possible to design studies to investigate whether prophylactic exercise can prevent or delay the onset of OA. Unfortunately, establishing the validity of this requires large, longitudinal trials that will be extremely complex, lengthy, expensive, and influenced by external variables that are all but impossible to control. Efficacy of exercise. There is good evidence that rehabilitation can ameliorate the effects of OA, so the most productive research agenda may be to develop our understanding of whether, how, and what exercise regimens can retard or reverse the effects of knee OA. It is still unclear if particular types of exercise benefit patients more than others. This article has argued for a combination of strengthening, endurance, balance, and coordination exercises, but comparing the relative efficacy of a predominantly strengthening exercise regimen with a regimen that aims to improve endurance may be informative. Enhancing exercise regimens. Integrating psychological or behavioral interventions (e.g., enhancing self efficacy, coping strategies, etc.) into an exercise regimen may enhance the efficacy and effectiveness of rehabilitation (83 87). How this is best achieved and for whom they work has not been elucidated. Patient targeting. To maximize the efficiency of rehabilitation, we may need to identify and target patients who will benefit most, when they will benefit most. This may involve identifying traits (e.g., anxiety, depression, inappropriate health beliefs) that might impede patient s ability accept and reap the benefits of exercise (88). Interventions could then be implemented to help maximize the benefit patients gain from exercise, or it might be decided to delay rehabilitation to prevent wasting valuable resources. Education programs. Integrating health education programs can enhance the use of physical activity in the management of knee OA if they are clearly explained, easily understood, and regularly reinforced by healthcare professionals (89). Development of clinically effective regimens. Much of the work looking at the efficacy of exercise in knee OA has looked at prolonged, hospital-based regimens, involving patients atypical of the majority of patients with knee OA who are managed in the community. The clinical effectiveness of these regimens is questionable. It would be of greater value to know the effectiveness of practical rehabilitation regimens, undertaken by more typical patients, under routine clinical conditions. To improve patient management we need to understand and address compliance. To do this, quantitative research methodologies can establish whether an intervention works and qualitative research methodologies enable us understand why some regimens are (not) efficacious and clinically effective. Maintenance of regular exercise in the community. Facilitating regular physical activity in the community will be fundamental to the management of knee OA. How to achieve this requires substantial investigation. Research methodology. Much of the foregoing research agenda can be evaluated using the traditional gold standard methods, i.e., randomized controlled trials (RCTs), which were developed to establish efficacy of drug trials. In an RCT, the effect of administering a very specific intervention on 1 or 2 carefully chosen physiologic variables is assessed in carefully selected patients, while the experimental environment is carefully controlled to minimize the influence of confounding variables. The demands of traditional research methodology are very restrictive and are not good at evaluating interventions such as exercise rehabilitation of OA, where the typical patient population is elderly, has several comorbidities, and resides in the community where exposure to confounding, uncontrollable, external variables might adversely influence their ability to comply with the intervention. We may need to

7 450 Hurley develop and utilize more appropriate methodologies to evaluate the clinical effectiveness of a complex health care intervention (90,91). When designing management regimens for patients with OA, the overriding principle must be the need for clinically effective regimens, and their evaluation must be achieved using the most appropriate research methodology. Interventions should not be devised because they are amenable to evaluation by accepted, but restrictive and possibly inappropriate, research methodology: the research question should dictate what methodology should be used. Methodologic issues must not dictate the research questions we ask. Utilization of novel research designs will require careful consideration (and not a little courage) by researchers, grant-awarding bodies, and journal editors during the design, funding, and publication of evaluations of interventions. Summary In knee OA, quadriceps sensorimotor dysfunction weakness, impaired proprioceptive acuity, and impaired neuromuscular protective reflexes is associated with pain and disability. Intuitively we usually assume that joint damage causes and precedes pain, resulting in reduced mobility and muscle weakness, but this assumption and may be incorrect because there is evidence that quadriceps dysfunction may play a role in the pathogenesis of knee OA. Exploiting muscle s fantastic physiologic plasticity, exercise provides us with powerful potential strategies to retard, prevent, and even reverse some of the pathologic processes in knee OA. If muscle dysfunction is involved in the pathogenesis of knee OA, then maintaining strong, well-conditioned muscles may prevent the onset of OA. For people with established OA, there is now convincing evidence that exercise improves muscle sensorimotor dysfunction and reduces pain and disability without exacerbating joint damage. We now need to develop and evaluate clinically effective exercise regimens that can be delivered to the large patient population in the community, and maximize the benefits of the regimen by identifying strategies that encourage and enable participation in regular physical activity. This will enable patients to appreciate the benefits of physical activity and actively participate in the self management of their condition. ACKNOWLEDGMENT The author thanks the 2 anonymous reviewers for their helpful comments on the draft manuscript. REFERENCES 1. Badley E, Rasooly I, Webster GK. Relative importance of musculoskeletal disorders as a cause of chronic health problems, disability, and health care utilization: findings from the 1990 Ontario Health Survey. J Rheumatol 1994;21: Peat G, McCarney R, Croft P. Knee pain and osteoarthritis in older adults: a review of community burden and current use of primary health care. 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