THE SYMPTOMS OF knee OA, such as pain and stiffness

Transcription

1 2185 ORIGINAL ARTICLE Physical Function and Properties of Quadriceps Femoris Muscle in Men With Knee Osteoarthritis Tuomas Liikavainio, MD, MSc, Tarja Lyytinen, BM, Erja Tyrväinen, MD, Sarianna Sipilä, PhD, Jari P. Arokoski, MD, DMSc ABSTRACT. Liikavainio T, Lyytinen T, Tyrväinen E, Sipilä S, Arokoski JP. Physical function and properties of quadriceps femoris muscle in men with knee osteoarthritis. Arch Phys Med Rehabil 2008;89: Objectives: To examine the objective physical function of the lower extremities, to measure the properties of quadriceps femoris muscle (QFM), and to assess subjective disabilities in men with knee osteoarthritis (OA) and to compare the results with those obtained from age- and sex-matched control subjects. Design: Cross-sectional study. Setting: Rehabilitation clinic in a university hospital. Participants: Male volunteers (n 54) (age range, 50 69y) with knee OA and randomly selected healthy, age- and sexmatched control subjects (n 53). Interventions: Not applicable. Main Outcome Measures: Physical function evaluated with a test battery including the QFM composition measurement, the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and the RAND 36-Item Short-Form Health Survey, version 1.0. Results: Knee OA patients had 13% to 26% poorer (P range, ) physical function and muscle strength compared with the controls. There were also significant differences in QFM composition. WOMAC (P range, ) and muscle strength (P.001) associated with physical function tests, but subjective pain correlated with neither physical function nor muscle strength in knee OA patients. The radiographic knee OA grade did not have any significant effect on physical function, but passive knee motion, knee extension strength, and WOMAC were related to the severity of the disease (P.05). Conclusions: The patients with knee OA exhibited impaired physical function and muscle strength and QFM composition compared with healthy controls. The severity of radiographic knee OA clearly had adverse effects on functional ability at the later stages of the disease. The results highlight the effect of QFM strength on physical function as well as the importance of patient s subjective and objective physical function when deciding on knee OA treatment policy. Key Words: Activities of daily living; Osteoarthritis, knee; Rehabilitation; Ultrasonography by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation THE SYMPTOMS OF knee OA, such as pain and stiffness of the joint and impaired muscle strength in the lower extremities are serious risk factors for mobility limitation and impaired QOL. 1 Based on the Health 2000 examination survey, the age-adjusted prevalence of clinically diagnosed knee OA was 6.1% and 8% in men and women over 30 years, respectively, but over 1 in every 10 Finnish men aged 55 to 74 years suffer from knee OA. 2 Thus, knee OA constitutes a major social and health problem in older people, imposing an increasingly heavy financial burden on the social welfare and health care systems in modern societies. 3,4 The ability to cope with routine daily physical activities is threatened in the course of aging and progression of OA disease. 3-5 Several authors have concluded that adequate muscle strength seems to be an important factor in the capability to perform ADLs. 5-9 Patients with knee OA exhibit weakness in the QFM, and muscle strengthening in knee OA patients has improved their physical function Weakness in the QFM has been shown to be a better determinant of pain and disability than any radiographic changes in knee OA, and reduced QFM strength will be a risk factor for knee OA. 22 Several mechanisms have been suggested to cause muscle weakness in knee OA, for example, the disuse atrophy of the muscles due to joint pain, 23,24 reflex inhibition of muscles moving the affected joint, and incapability to fully activate the QFM resulting in the decreased force production. 12,26,27 Knee joint laxity is also associated with a decrease in the magnitude of the relationship between strength and physical function in knee OA. 28 Though there may be many possible explanations and contributing factors, the ultimate mechanism From the Department of Physical and Rehabilitation Medicine, Kuopio University Hospital, Kuopio (Liikavainio, Arokoski, Lyytinen); Kolari Health Centre, Kolari (Liikavainio); Department of Clinical Radiology, Kuopio University Hospital, Kuopio (Tyrväinen); The Finnish Centre for Interdisciplinary Gerontology, Department of Health Sciences, University of Jyväskylä, Jyväskylä (Sipilä); and Institute of Clinical Medicine, University of Kuopio, Kuopio (Arokoski), Finland. Presented as a poster to the World Congress in Osteoarthritis, December 7 10, 2006, Prague, Czech Republic. Supported by EVO from Kuopio University Hospital (grant no ) and by the Prosthesis Foundation. No commercial party having a direct financial interest in the results of the research supporting this article has or will confer a benefit on the authors or on any organization with which the authors are associated. Reprint requests to Tuomas Liikavainio, MD, MSc, Dept of Physical and Rehabilitation Medicine, Kuopio University Hospital, PO Box 1777, FIN Kuopio, Finland, liikavai@hytti.uku.fi /08/ $34.00/0 doi: /j.apmr ADLs BMI HRQOL OA QFM QOL ROM RAND-36 TUG VAS WOMAC List of Abbreviations activities of daily living body mass index health-related quality of life osteoarthritis quadriceps femoris muscle quality of life range of motion RAND 36-Item Short-Form Health Survey Timed Up & Go visual analog scale Western Ontario and McMaster Universities Osteoarthritis Index

2 2186 PHYSICAL FUNCTION IN KNEE OSTEOARTHRITIS, Liikavainio behind the muscle weakness in knee OA is not fully understood. As far as we are aware, there are no reports in the literature where possible alterations in QFM composition and size have been evaluated in patients with knee OA compared with healthy controls. Furthermore, the effects of severity of knee OA in QFM properties are not known. Previously, Arokoski et al 29 have reported that patients with hip OA demonstrate decreased muscle strength compared with healthy controls, as well as diminished cross sectional area of pelvic and thigh muscles in the more deteriorated side. In addition to impaired muscle strength of the QFM, the general physical function of limbs is also believed to be restricted. However, we have found quite a few studies that have investigated the extent to which tested physical function, for example, walking, jumping, and knee bending, is affected in patients with knee OA and have compared these results with the corresponding values of healthy controls, but to our knowledge the effect of the severity of knee OA on the objective physical function has not been reported previously. In the recent review of the measurement properties of physical function tests in patients with hip or knee OA, Terwee et al 33 concluded that many additional well-designed studies will be required to assess the measurement properties of performancebased methods. To our knowledge, there are no previous studies in which the control subjects do not exhibit any radiographic knee OA findings. It is also not clear which of the possible confounding factors, for example, pain, comorbidity, physiopathologic, sociodemographic, psychologic, and social factors, has the greatest influence on the physical function of patients suffering from knee OA. In addition, the association between the knee muscle properties (strength, composition) and physical performance is not fully understood in knee OA sufferers, though some studies have indicated that the severity of the pain is directly correlated with decreased physical function. 9,34 In knee OA, quadriceps strength seems to be strongly associated with knee pain, even when activation and psychologic factors are taken into account. 25 In addition, an association between obesity and physical function in knee OA has been found in some studies. 34,35 The main aim of the present study was to examine the physical function and the properties of the QFM in men with knee OA and to compare the results with these from age- and sex-matched, randomly selected healthy controls. Second, the purpose was to estimate the effect of possible confounding factors (ie, knee pain, anthropometry, background information) on the observed differences in physical function between the groups. By combining the results of questionnaires, including WOMAC and RAND-36, as well as those of objectively determined physical function tests, it was possible to obtain a more comprehensive perspective of the physical capacity of the OA patient. We anticipated that the functional capacity and the properties of the QFM could be reduced in patients with knee OA. We also hypothesized that the confounding factors would associate more closely with impaired physical capacity than the radiographic severity of the disease. METHODS Participants and Selection We recruited study subjects by a local newspaper advertisement from the city of Kuopio, Finland and its neighboring area between December 2004 and April Subjects (n 54) were selected by clinical criteria for uni- or bilateral knee OA. Subjects had experienced pain or functional impairment (eg, limitation of knee motion or stiffness of the joint) in the knee region within the prior month as indicated in the clinical criteria of the American College Table 1: Characteristics of Knee OA Patients and Control Subjects Variable* Control Group (n 53) Knee OA Group (n 54) Age (y) Weight (kg) Height (m) BMI (kg/m 2 ) Knee flexion (deg) Knee extension (deg) Knee alignment (deg) RAND-36 Physical functioning Role functioning/physical Role functioning/emotional Vitality Mental health Social functioning Bodily painlessness General health NOTE. Values are mean SD. *See Methods for details. Student t test for 2 independent samples. Mann-Whitney nonparametric test. of Rheumatology. 36 The exclusion criteria of knee OA patients and control subjects are shown in appendix 1. All OA subjects were able to walk without physical assistance or devices. The characteristics of the subjects are presented in table 1. Control men with no OA were randomly sampled from the population register of the city of Kuopio (N 10,505). Initially, 528 men aged 51 to 70 years were contacted by letter of invitation between August 2005 and February 2006, which also stated the exclusion criteria. Eighty-seven men (16.5%) replied to the letter and of these, 34 (39.1%) were excluded because of a nonsymptomatic radiographic hip or knee OA score of 1 or more in either limb (Kellgren and Lawrence scale, 37 see Evaluation of Plain Radiographs section). Controls did not exhibit hip or knee OA according to the clinical criteria of the American College of Rheumatology. 36 Ultimately, 53 healthy age-matched 51- to 67- year-old men participated in the study as controls (see table 1). The ethics committee of Kuopio University Hospital approved the study design, which conformed to the Declaration of Helsinki. Questionnaires All subjects completed questionnaires on comorbidities, leisure-time physical activity, and questions concerning work history. Five disorder classes were listed: cardiovascular, respiratory, gastrointestinal, endocrinologic diseases, and depression. Leisure-time physical activity was assessed from a 12-month history modified from the Minnesota Leisure Time Physical Activity Questionnaire. 38 The frequency of leisure-time physical activity (sessions a year) was determined. A basic questionnaire was used to elicit information on the occupations (scale 0 [no work] to 6 [in physical terms the most demanding occupation]). 39 In OA subjects, use of prescribed pain relief medication (yes, no) was determined for the previous 6 months as well as the occurrence of possible knee joint traumas (yes, no). Knee symptoms were estimated by patients with the WOMAC, 40 which is a tri-dimensional, disease-specific health status questionnaire consisting of 24 questions in the areas of pain, stiffness, and physical function in patients with OA of the P

3 PHYSICAL FUNCTION IN KNEE OSTEOARTHRITIS, Liikavainio 2187 knee. A composite score was generated by summing all of the responses and then dividing by 24 (total number of items). Self-reported generic physical function was determined by using the physical function part of the RAND-36 questionnaire containing exactly the same questions as the Medical Outcome Study 36-Item Short-Form Health Survey, 41,42 but the scoring for the general health and bodily pain subscales differs slightly. The reliability and construct validity of the RAND-36, as a measurement of the HRQOL in the general population, have been established. 43 Evaluation of Plain Radiographs The standard anteroposterior weight bearing (full extension; tube voltage, 60kV; quantity of electric charge, 25mAs; focusskin distance, 110cm) and lateral radiographs as well as the weight-bearing radiographs of lower limbs were taken from both knees. The radiographs were evaluated by a blinded experienced radiologist using the Kellgren and Lawrence grading, 37 in which 0 means no OA and 4 refers to severe OA (ET). The intrarater reliability of Kellgren and Lawrence grading has been established to be high. 44 The knee varus or valgus alignment was measured using the method described by Moreland et al, 45 and alignment was expressed as an absolute value (in degrees) of the divergence from the straight line (0 ). Measurement of Knee Joint ROM The same investigator measured the ROM of the knee joint with a standard goniometer. The knee flexion ROM was the value of active bending of the knee while the patient was lying supine. 46 Knee extension ROM was the angle of passive straightening of the knee while the patient was lying supine. 47 Ultrasound Measurements We measured properties of the QFM with ultrasound a from the midpoint of the rectus femoris, vastus lateralis, and vastus intermedius compartments using a 5cm wide probe of 5-MHz frequency. The measurement point was midway between the lateral joint space and the trochanter major. During the measurement, the subjects lay in a supine position with the legs totally relaxed. The probe was then assumed to be at right angles to the femur. The thickness of the subcutaneous fat and the thickness of the muscle group, including the rectus femoris, vastus lateralis, and vastus intermedius, were assessed by means of a longitudinal real-time scan. The ultrasound images were further analyzed with Scion Image b software for Windows. The area (in cm 2 ) beneath the probe and the mean echogenicity of the 3 compartments (rectus femoris, vastus lateralis, vastus intermedius) were determined to evaluate muscle mass and tissue composition. The method and its reproducibility have been described in more detail elsewhere. 48,49 Quantitative ultrasonography has been shown to correlate with computed tomography in muscle cross-sectional area and muscle composition measurements. 50 Physical Function Tests Prior to performance of the physical function tests, we familiarized the subjects with the test procedure and purpose. Adequate pauses between tests were allowed in order to avoid fatigue. The same investigator directed the testing sessions, providing similar verbal encouragement to every subject to do his best (JA). The physical functioning was measured using a standardized test battery performed in a randomized order except for the 5-minute walk and muscle strength measurements which were carried out at the end of the session. The patients assessed their subjective knee pain before strength measurements with VAS, in which 0 refers to no pain and 100 the worst possible knee pain. The tests were as follows: Lift test. This test was modified from the lift test by Strand et al. 51 Each subject was asked to repeat lifting a box (8.5kg) from the floor to a table (.73m) and back to the floor for 1 minute. The number of lifts was recorded. Pick-up test. In the pick-up test, 52 each subject picked up a piece of paper from the floor in the most comfortable way. The investigator assessed the performance with a scale 0 to 3, in which 0 denotes performance with flexibility and ease and 3 denotes inability to do the task or the need for external support. Repeated sit-to-stand test. In the repeated sit-to-stand test, 28,53-56 each subject was asked to fold arms across his or her chest and to stand up from the sitting position and to sit down 5 times as quickly as possible. The mean value in seconds to complete the 2 trials was registered. Sock test. In the sock test, 57 the participant was asked to simulate putting on a sock in a standardized manner. The test was performed for both sides. Scores are awarded in ordinal values from 0 to 3. A score of 0 indicates that the patient could grab toes with fingertips and performed the action with ease. A score of 3 indicates that the patient could hardly, if at all, reach as far as the malleoli. Stair ascending and descending tests. For the stair ascending and descending tests, 58,59 subjects walked up and down 12 stairs as quickly as possible. Both tasks (separately ascending and descending stairs) were performed 3 times and the mean velocity (in m/s) of 3 trials was used as the result of the test. Straight line walking. For straight line walking, 60 each subject walked for 10m as straight as possible following a straight line on the floor. The time required to complete the 10-m task was recorded and the mean of 3 trials was calculated. Timed Up & Go test. For the TUG test, using a standard-high chair with arm rests, participants were asked to stand up from the chair, walk 3m, turn, walk back, and sit down quickly and safely. The mean time in seconds from 3 performances was calculated. Twenty-meter walk test. For the 20-m walk test, 65 subjects were asked to walk 20m as quickly as possible. The task was performed 3 times and the mean speed (in m/s) was used as the result of the test. This walk test has been successfully used to assess the walking ability of disabled and elderly patients. 66,67 Five-minute walk test. For the 5-minute walk test, 55,65 subjects walked back and forth on a 20-m course for 5 minutes. The participants were asked to walk as quickly and safely as you can for 5 minutes. Two level-walking tests were chosen because we wanted to analyze which of them would better describe functional impairment in knee OA. The score recorded was the total distance traveled (in meters) during 5 minutes. Maximal voluntary isometric knee extension and flexion tests. For the maximal voluntary isometric knee extension and flexion tests, 68,69 the force measurements were performed on the subject in the sitting position by using a calibrated dynamometer. c The thigh was fixed on the seat in the distal part of the femur. The ankle was attached to the moment arm just above the malleolus. The knee and hip angles were fixed at 70. Both legs were tested separately and the trial order was randomized. The subjects performed as many maximal actions until the peak value no longer increased and the best result (in Nm) was registered and the results were expressed as Nm/kg. Statistical Analysis We used the Kolmogorov-Smirnov and Levene tests to assess the normality of distribution and the equality of variances, respectively. The knee OA patients were compared to healthy controls with the Student t test for 2 independent samples. The subjects

4 2188 PHYSICAL FUNCTION IN KNEE OSTEOARTHRITIS, Liikavainio were further divided into 4 subgroups (Kellgren and Lawrence scores of 1 4) according to the classification in Kellgren and Lawrence scale. For each patient, the knee with the highest radiographic OA score, or with clinical symptoms if scores were the same, was used for the analysis. A 1-way analysis of variance was used to test for possible differences in continuous parameters between the 4 knee OA subgroups (ie, Kellgren and Lawrence scores of 1 4). The corresponding nonparametric test was used for ordinal scale parameters and for variables which were not normally distributed in the preceding comparisons (ie, Mann- Whitney, Kruskal-Wallis, and Wilcoxon, respectively). The differences were compared with those of the knee on the same side of an age-matched control subject. The results were considered significant if P was less than.05. All statistical analyses were performed with SPSS d software for Windows. RESULTS Characteristics of the Study Participants The clinical features of the groups are shown in table 1. The patients with knee OA had 9.6% (P.001) higher BMI than the control subjects. OA subjects showed significantly poorer HRQOL in 7 of the 8 separate scales as measured by the RAND- 36, version 1.0. The HRQOL did not differ between the knee OA subgroups. There were no significant differences between the groups in terms of leisure-time physical activity (OA subjects, sessions/y vs control subjects, sessions/y). The work load history was significantly higher (P.01) in knee OA patients compared with controls ( vs , respectively), but patients were not suffering from more chronic diseases than were the controls. The characteristics of the knee OA subgroups (Kellgren and Lawrence scores of 1 4) are presented in table 2. The knee absolute value of varus or valgus alignment was 42.6% lower (P.003) in the knee with the lower OA grade (Kellgren and Lawrence score of 1) compared with the knee with the higher OA grade (Kellgren and Lawrence score of 4). In OA patients, the knee flexion and extension ROM values were 12.4% and 42.9% lower (P.05) in the knee with the higher OA grade (Kellgren and Lawrence score of 4) compared with the knee with the lower OA grade (Kellgren and Lawrence score of 1), respectively. There were no significant differences among the 4 subgroups in terms of age, weight, height, BMI, VAS, leisure-time physical activity, use of pain medication, number of comorbidities, or work load history between the OA and control groups. Physical Function Tests The results of the physical function tests of the OA and control groups are shown in fig 1. One control subject did not perform the 20-m walk trial (technical reason). One knee OA patient (Kellgren and Lawrence score of 3) was not able to complete the stair walking trials and 1 (Kellgren and Lawrence score of 2) was not able to perform a 5-minute walk task. Repeated sit-to-stand test was too demanding for the 1 patient with the most severe knee OA (Kellgren and Lawrence score of 4). The patients with knee OA exhibited significantly (P.001; pick-up test, P.002) poorer performance than controls in all the physical function tests (see fig 1). The difference between the mean values of the groups varied from 16% to 20% for the 5-minute walk, 20-m walk, stair ascending and descending, and lift tests. The control subjects were 19% to 26% faster in the TUG test, straight line walking tests, and repeated sit-to-stand than patients suffering from knee OA. The patients with knee OA showed significantly poorer physical function than control subjects also in the sock test (see fig 1). There were no statistical differences in any physical function test between the knee OA subgroups, although the patients with the most severe knee OA (Kellgren and Lawrence score of 4) tended to exhibit the worst performance in every task (see fig 1). Western Ontario and McMaster Universities Osteoarthritis Index The WOMAC detected the differences in subjective assessed knee OA symptoms between the subgroups (fig 2). The stiffness, function, and composite scores, but not the pain scores, were associated with the severity of knee OA (P.05). The post hoc analysis with Mann-Whitney U test revealed that only Table 2: Characteristics of Knee OA Subgroup Patients Knee OA Subgroup Variable* K&L Score of 1 (n 12) K&L Score of 2 (n 15) K&L Score of 3 (n 19) K&L Score of 4 (n 8) P Age (y) Weight (kg) Height (m) BMI (kg/m 2 ) Knee pain, VAS (mm) Knee alignment (deg) Knee flexion (deg) Knee extension (deg) LTPA (sessions/y) Pain medication (yes, no), % of the patients Comorbidities (n) Work load history (0 6) Knee trauma (yes, no), (% of the patients) NOTE. Values are mean SD or as otherwise indicated. Abbreviation: K&L, Kellgren and Lawrence; LTPA, leisure-time physical activity. *See Methods for details. One-way analysis of variance. Kruskal-Wallis. Chi-square. Knee pain was separately inquired during functional tests.

5 PHYSICAL FUNCTION IN KNEE OSTEOARTHRITIS, Liikavainio 2189 Fig 1. Physical function tests (mean SD) in controls (n range, 52 53) and in men with knee OA (n range, 53 54). The knee OA patients were further divided into 4 subgroups according to the radiographic severity of their knee OA using Kellgren and Lawrence scale 37 (Kellgren and Lawrence scores of 1 4). The patients with knee OA exhibited significantly poorer performance than controls in all physical function tests. There were no statistically significant differences between knee OA subgroups in any of the tests. *P<.001 (Student t test for 2 independent samples); P<.001 (Mann-Whitney nonparametric test); P<.01 (Mann-Whitney nonparametric test). the subgroup with a Kellgren and Lawrence score of 4 diverged from all the other groups in the WOMAC. The WOMAC scores correlated significantly with physical function tests (table 3). The highest associations with WOMAC were found in 20-m walk (r range,.514 to.607), 5-minute walk (r range,.485 to.577), and repeated sit-to-stand tests (r range, ). The knee extension and flexion torque correlated inversely with all WOMAC scores. Passive knee joint extension exhibited moderate association with stiffness; otherwise there was only a weak or no correlation at all between WOMAC and knee joint ROM. BMI showed also a linear correlation with physical function tests (P range, ), with the exception of the lift test (P.109).

6 2190 PHYSICAL FUNCTION IN KNEE OSTEOARTHRITIS, Liikavainio (P.05) negative linear trend as the severity of knee OA increased. Fig 2. WOMAC scores (mean SD) in groups with different grades of knee OA. The radiographic grading was made according to the Kellgren and Lawrence scale. 37 *P<.05 (Kruskal-Wallis test). Muscle Strength and Composition The control subjects showed significantly (P.05) higher knee extension (P.001) and flexion torques (table 4). Knee extension or flexion torques did not diverge between knee OA subgroups, but the knee extension torque exhibited a significant negative linear trend (P.05) as the severity of knee OA increased. There were no significant differences between the groups in the absolute muscle thickness (in centimeters) and area (in cm 2 ) under the probe (see table 4). The rectus femoris and vastus intermedius, but not the vastus lateralis muscle compartments of the QFM, exhibited significantly (P.05) more heterogeneity in the knee OA group compared with the controls. There were no statistical differences in the thickness of the subcutaneous fat either between OA and control groups or between the OA subgroups (data not shown). The QFM composition and size did not differ between knee OA subgroups. However, vastus lateralis composition, for example, echogenicity and rectus femoris thickness, both exhibited a significant Physical Function Tests Correlations Among the patients with knee OA, muscle strength was associated with physical function tests (all P.001) as well as with knee alignment (table 5). The strongest correlations were found in the 5-minute walk (r range, ), TUG test (r range,.649 to.693), and 20-m walk (r range, ). The isometric knee flexion torque was only in weak or moderate association with the lift test and repeated sit-to-stand task (r.298, r.361, respectively) in the control subjects. Knee extension torque showed also a weaker correlation with the physical function in healthy controls compared with knee OA subjects. The best correlation coefficient values were found in the 20-m walk test (r.485, P.001) among the control group. The absolute knee alignment degree had only a weak or moderate association (P range, ) with the functional tests (r range,.216 to.387 ), in fact there was a nonsignificant correlation with the pick-up test (r.109, P.05). Muscle strength measurements were not in association with muscle compositions, and subjective knee pain (VAS) did not correlate with physical function, muscle strength measurements, or knee joint ROM (data not shown). DISCUSSION The patients with knee OA exhibited significantly poorer physical function and lower knee extension and flexion muscle strength compared with age- and sex-matched control subjects. The mean decline of performance ranged from about 13% to 26% in the patient group. Furthermore, the RAND-36 survey revealed that patients with knee OA showed significantly impaired HRQOL in almost all of the measured separate scales compared with the control subjects. There were also significant differences in QFM composition between the groups. As far as we are aware, this is the first population-based study in which the knee muscle strength and physical function tests of limbs with simultaneous muscle composition measurements have been evaluated in patients with knee OA comparing the results with age- and sex-matched controls. The study design provides more comprehensive understanding of the OA disease by incorporating the disability and HRQOL. Table 3: Correlations Between the WOMAC and Functional Tests and Knee Joint ROM in Patients With Knee OA (n range, 53 54) Functional Tests and Joint Motion* WOMAC Pain Stiffness Function Composite Lift test (no. of repetitions) Pick-up test (0 3) Repeated sit-to-stand (s) Sock test (0 3) Stair ascending (m/s) Stair descending (m/s) Straight line walking (s) TUG test (s) m walk (m/s) min walk (m) Knee extension torque (Nm/kg) Knee flexion torque (Nm/kg) Knee extension (deg) NS.308 NS NS Knee flexion (deg) NS NS Abbreviation: NS, nonsignificant (Spearman correlation coefficient). *See Methods for details. P.05; P.01; P.001.

7 PHYSICAL FUNCTION IN KNEE OSTEOARTHRITIS, Liikavainio 2191 Table 4: Composition of the QFM and Knee Flexion and Extension Strength in Healthy Controls (n 53) and Knee OA Subjects (n 54) Knee OA Subgroup Variable* Controls Knee OA P K&L Score of 1 K&L Score of 2 K&L Score of 3 K&L Score of 4 P Rectus femoris thickness (cm) Rectus femoris area (cm 2 ) Rectus femoris composition (grey scale) Vastus lateralis thickness (cm) Vastus lateralis area (cm 2 ) Vastus lateralis composition (grey scale) Vastus intermedius thickness (cm) Vastus intermedius area (cm 2 ) Vastus intermedius composition (grey scale) Knee extension (Nm/kg) Knee flexion (Nm/kg) NOTE. Values are mean SD. The results of 4 knee OA subgroups (Kellgren and Lawrence scores of 1 4) are compared to each other. Abbreviation: K&L, Kellgren and Lawrence. *See Methods for details. Student t test for 2 independent samples; Mann Whitney nonparametric test; Kruskal-Wallis nonparametric test; one-way analysis of variance. The physical functioning was measured using a battery of validated tests that could be practically applied in general practice. The tests used required joint mobility, the strength of lower extremities, and balance and were intended to mimic normative daily activities. However, it is possible that they do not properly measure aerobic capacity, which is also needed in normalized daily life. It is possible that the differences would have been more marked, if the tasks had been prolonged to several minutes. Therefore, our performance test results are unlikely to overestimate the true differences between the groups. The grade of knee OA had a significant impact on ROM. This might indicate that evaluation of the knee ROM is a sensitive clinical criterion in determining by radiography the severity of knee OA. Previously, the ROM has been shown to influence the functional ability in the knee OA. The patients with knee OA are known to exhibit decreased ROM and increased mediolateral laxity compared with controls. 70,71 Steultjens et al 72 have also concluded that restricted joint mobility is an important component in the disability in patients suffering from knee OA. However, in the current study, the absolute changes were quite small between the groups, with Kellgren and Lawrence scores of 1 to 3. Second, because the WOMAC main dimensions were poorly correlated with the knee ROM, the use of knee ROM as the only functional test is questionable. The grade of knee OA did not have any significant effect on the tested physical function, even though the patients with the highest grade of knee OA seemed to exhibit the worst performance in every task. Only the maximal voluntary isometric knee extension torque and knee joint ROM were related to the severity of knee OA. Similarly, there were no major differences between the self-reported function (WOMAC) in patients with radiographic scores of the groups with Kellgren and Lawrence scores of 1 through 3, but in the tertiary-stage (Kellgren and Lawrence score of 4) the extent of the self-reported functional disability was significantly higher. These findings are in agreement with earlier studies. 73,74 In our study, the WOMAC function scale, but not physical functioning according to RAND-36, was in association with the radiographic knee OA Table 5: Correlations Between the Knee Extension and Flexion Strength Measurements and Functional Tests and Knee Alignment in the Patients With Knee OA (n range, 53 54) and the Healthy Controls (n range, 52 53) Functional Tests and Knee Alignment* Knee OA Controls Knee Extension (Nm/kg) Knee Flexion (Nm/kg) Knee Extension (Nm/kg) Knee Flexion (Nm/kg) Lift test (no. of repetitions) Pick-up test (0 3) Repeated sit-to-stand (s) Sock test (0 3) NS NS Stair ascending (m/s) NS NS Stair descending (m/s) NS Straight line walking (s) NS NS TUG test (s) NS 20-m walk (m/s) NS 5-min walk (m) NS Knee alignment (deg) NS NS Abbreviation: NS, nonsignificant (Pearson correlation coefficient). *See methods for details. P.05; P.01; P.001, P.05; P.001 (Spearman correlation coefficient).

8 2192 PHYSICAL FUNCTION IN KNEE OSTEOARTHRITIS, Liikavainio severity. Thus, disease-specific WOMAC function index seems to be a more sensitive indicator of radiographic severity of knee OA than most of the physical function tests and RAND-36. In our study, there were no statistical differences in age, anthropometry, or subjective pain between the knee OA subgroups. Furthermore, the background information about leisure time physical activity, pain medication, primary diseases, work history, and knee trauma did not reveal any divergences between the subgroups. Therefore, our initial hypothesis that the confounding factors would associate more closely with impaired physical capacity than with the radiographic severity of the disease was not supported. The different WOMAC dimensions correlated with the objective physical function tests, but only weakly or not at all to knee joint ROM. The association with physical function was more evident than previously reported by Arokoski et al 58 in hip OA patients or according to Lin et al 75 in hip and/or knee OA patients. Because these authors had either smaller 58 or more heterogeneous 75 study groups, and they used slightly different test batteries, no direct comparisons can be made with our results. Interestingly, the mean WOMAC pain score of all knee OA patients was over 4 times higher ( mm) than the mean subjective pain ( mm) assessed with VAS during the measurements. This also supports our idea that the results do not overestimate the true impairment in physical function of knee OA patients. Knee extension and flexion strength were 19.6% and 12.8% reduced in patients with knee OA, respectively. Furthermore, the values of knee extension and flexion strength were in association with the results of physical function tests in the patient group. This finding confirms the conclusion of many authors 5,6,8,9 that adequate muscle strength seems to be an important factor in the capability to perform ADLs. However, the correlation between muscle strength and physical function seemed to be weaker in the control group. This would support the concept that there is a threshold in the force level that needs to be achieved in order to cope properly with daily activities. It has been postulated that patients with knee OA are not able to fully activate their QFM. 12,26,27 Unfortunately, we did not have the opportunity to examine the QFM activation level with a twitch interpolation technique during maximal voluntary force production. However, on average the subjective pain score described by the patients was quite low, and the subjects were verbally encouraged to achieve their maximum torque. In addition, the subjects performed so many maximal actions that the peak value did not increase and the best result was registered. These factors would tend to decrease the possible deficit in the activation level during force measurements. The muscle composition exhibited significant differences in the patients with knee OA. It was anticipated that the knee OA patients would exhibit muscle atrophy, which would be revealed as an increased echogenicity and decreased muscle thickness in the ultrasound assessment. Previously, Sipilä and Suominen 48 have shown that power-trained elderly men display a more homogeneous internal structure of the QFM than untrained men, indicating that long-term training can maintain the muscle composition and counteract the age-related replacement of contractile tissue by other tissues such as fat. The muscle thicknesses of the vastus lateralis and vastus intermedius compartments were higher in the controls after adjustment for weight. This is consistent with the higher force production seen in the control subjects. As far as we are aware, this is the first attempt to measure QFM composition in knee OA patients with ultrasound. The method has proven to be reliable 49 and it could give information of muscle internal structure noninvasively and inexpensively. The absolute knee alignment degree was associated with the functional tests, except for the nonsignificant correlations with the pick-up test. The knee alignment has proven to be an important factor in the development and progression of knee OA. 76 Our results support the finding that knee alignment could predict the decline of functional ability. 77 It can be concluded that knee alignment may be a good indicator of disease severity and functional performance. We also recommend using repeated-sit-to-stand test and 20-m walk test in clinical practice, because they are very reproducible tests 54,56,65 and easy to perform. They also exhibited an excellent correlation with WOMAC and muscle strength, which have been proven to be important indicators of disability in patients with knee OA ,40 Study Limitations We examined the physical function of men with knee OA aged 50 to 69 years, and therefore generalizations of the results to the female patients suffering from knee OA or to the patients in different age groups should be made cautiously. CONCLUSIONS The patients with knee OA exhibited impaired physical function and muscle strength, as well as deteriorated QFM composition compared to healthy controls. The severity of radiographic knee OA was clearly reflected in objectively and subjectively assessed disability, but only in the later stage of the disease. The results highlight the effect of QFM strength on physical function as well as the importance of subjective and objective physical functioning abilities of the patient when considering the appropriate knee OA treatment policy. Acknowledgment: We thank Vesa Kiviniemi, PhL, from the University of Kuopio, for his significant help in the statistical analyses. APPENDIX 1: EXCLUSION CRITERIA OF THE KNEE OA AND CONTROL SUBJECTS A history of previous hip or knee fracture Surgery of lower extremities (knee arthroscopy was allowed) Surgery to the vertebral column A history of other trauma to the hip joint or in the pelvic region Clinical or radiological hip OA A knee or hip joint infection Congenital or developmental disease of lower limbs Paralysis of lower extremities Any disease or medication that might have worsened physical function and interfered with the evaluation of knee pain, such as: Cancer Severe mental disorder Rheumatoid arthritis or spondylarthritis Symptomatic cerebrovascular disease Endocrine disease Epilepsy Parkinson disease Polyneuropathia, neuromuscular disorder Debilitating cardiovascular disease in spite of medication Atherosclerosis of lower extremities Painful back or acute sciatic syndrome Corticosteroid medication Symptomatic spinal stenosis References 1. Gorevic PD. Osteoarthritis. A review of musculoskeletal aging and treatment issues in geriatric patients. Geriatrics 2004;59:28-32; quiz 35.

9 PHYSICAL FUNCTION IN KNEE OSTEOARTHRITIS, Liikavainio Riihimäki H, Heliövaara M, working group. Musculoskeletal diseases. In: Aromaa A, Koskinen S, editors. Health and functional capacity in Finland. Baseline results of the Health 2000 health examination survey. Helsinki: KTL-National Public Health Institute; p Felson DT, Zhang Y. An update on the epidemiology of knee and hip osteoarthritis with a view to prevention. Arthritis Rheum 1998;41: Hamerman D. Clinical implications of osteoarthritis and ageing. Ann Rheum Dis 1995;54: McAlindon TE, Cooper C, Kirwan JR, Dieppe PA. Determinants of disability in osteoarthritis of the knee. Ann Rheum Dis 1993; 52: Messier SP, Glasser JL, Ettinger WH Jr, Craven TE, Miller ME. Declines in strength and balance in older adults with chronic knee pain: a 30-month longitudinal, observational study. Arthritis Rheum 2002;47: Sharma L, Cahue S, Song J, Hayes K, Pai YC, Dunlop D. Physical functioning over three years in knee osteoarthritis: role of psychosocial, local mechanical, and neuromuscular factors. Arthritis Rheum 2003;48: Steultjens MP, Dekker J, van Baar ME, Oostendorp RA, Bijlsma JW. Muscle strength, pain and disability in patients with osteoarthritis. Clin Rehabil 2001;15: van Baar ME, Dekker J, Lemmens JA, Oostendorp RA, Bijlsma JW. Pain and disability in patients with osteoarthritis of hip or knee: the relationship with articular, kinesiological, and psychological characteristics. J Rheumatol 1998;25: Fisher NM, Pendergast DR. Reduced muscle function in patients with osteoarthritis. Scand J Rehabil Med 1997;29: Hortobagyi T, Garry J, Holbert D, Devita P. Aberrations in the control of quadriceps muscle force in patients with knee osteoarthritis. Arthritis Rheum 2004;51: Lewek MD, Rudolph KS, Snyder-Mackler L. Quadriceps femoris muscle weakness and activation failure in patients with symptomatic knee osteoarthritis. J Orthop Res 2004;22: Slemenda C, Brandt KD, Heilman DK, et al. Quadriceps weakness and osteoarthritis of the knee. Ann Intern Med 1997;127: Tan J, Balci N, Sepici V, Gener FA. Isokinetic and isometric strength in osteoarthrosis of the knee. A comparative study with healthy women. Am J Phys Med Rehabil 1995;74: Fisher NM, White SC, Yack HJ, Smolinski RJ, Pendergast DR. Muscle function and gait in patients with knee osteoarthritis before and after muscle rehabilitation. Disabil Rehabil 1997;19: Fransen M, McConnell S, Bell M. Therapeutic exercise for people with osteoarthritis of the hip or knee. A systematic review. J Rheumatol 2002;29: Hurley MV, Scott DL. Improvements in quadriceps sensorimotor function and disability of patients with knee osteoarthritis following a clinically practicable exercise regime. Br J Rheumatol 1998; 37: van Baar ME, Dekker J, Oostendorp RA, et al. The effectiveness of exercise therapy in patients with osteoarthritis of the hip or knee: a randomized clinical trial. J Rheumatol 1998;25: Hurley MV, Newham DJ. The influence of arthrogenous muscle inhibition on quadriceps rehabilitation of patients with early, unilateral osteoarthritic knees. Br J Rheumatol 1993;32: Lankhorst GJ, Van de Stadt RJ, Van der Korst JK. The relationships of functional capacity, pain, and isometric and isokinetic torque in osteoarthrosis of the knee. Scand J Rehabil Med 1985; 17: Madsen OR, Bliddal H, Egsmose C, Sylvest J. Isometric and isokinetic quadriceps strength in gonarthrosis; inter-relations between quadriceps strength, walking ability, radiology, subchondral bone density and pain. Clin Rheumatol 1995;14: Slemenda C, Heilman DK, Brandt KD, et al. Reduced quadriceps strength relative to body weight: a risk factor for knee osteoarthritis in women? Arthritis Rheum 1998;41: Hurley MV. The role of muscle weakness in the pathogenesis of osteoarthritis. Rheum Dis Clin North Am 1999;25:283-98, vi. 24. O Reilly S, Jones A, Doherty M. Muscle weakness in osteoarthritis. Curr Opin Rheumatol 1997;9: O Reilly SC, Jones A, Muir KR, Doherty M. Quadriceps weakness in knee osteoarthritis: the effect on pain and disability. Ann Rheum Dis 1998;57: Fitzgerald GK, Piva SR, Irrgang JJ, Bouzubar F, Starz TW. Quadriceps activation failure as a moderator of the relationship between quadriceps strength and physical function in individuals with knee osteoarthritis. Arthritis Rheum 2004;51: Mizner RL, Petterson SC, Stevens JE, Vandenborne K, Snyder- Mackler L. Early quadriceps strength loss after total knee arthroplasty. The contributions of muscle atrophy and failure of voluntary muscle activation. J Bone Joint Surg Am 2005;87: Sharma L, Hayes KW, Felson DT, et al. Does laxity alter the relationship between strength and physical function in knee osteoarthritis? Arthritis Rheum 1999;42: Arokoski MH, Arokoski JP, Haara M, et al. Hip muscle strength and muscle cross sectional area in men with and without hip osteoarthritis. J Rheumatol 2002;29: Bremander AB, Dahl LL, Roos EM. Validity and reliability of functional performance tests in meniscectomized patients with or without knee osteoarthritis. Scand J Med Sci Sports 2007;17: Piva SR, Fitzgerald GK, Irrgang JJ, Bouzubar F, Starz TW. Get up and go test in patients with knee osteoarthritis. Arch Phys Med Rehabil 2004;85: Thomas SG, Pagura SM, Kennedy D. Physical activity and its relationship to physical performance in patients with end stage knee osteoarthritis. J Orthop Sports Phys Ther 2003;33: Terwee CB, Mokkink LB, Steultjens MP, Dekker J. Performancebased methods for measuring the physical function of patients with osteoarthritis of the hip or knee: a systematic review of measurement properties. Rheumatology (Oxford) 2006;45: Creamer P, Lethbridge-Cejku M, Hochberg MC. Determinants of pain severity in knee osteoarthritis: effect of demographic and psychosocial variables using 3 pain measures. J Rheumatol 1999; 26: Jordan JM, Luta G, Renner JB, et al. Self-reported functional status in osteoarthritis of the knee in a rural southern community: the role of sociodemographic factors, obesity, and knee pain. Arthritis Care Res 1996;9: Altman R, Alarcón G, Appelrouth D, et al. The American College of Rheumatology criteria for the classification and reporting of osteoarthritis of the hip. Arthritis Rheum 1991;34: Kellgren JH, Jeffrey MR, Ball J. The epidemiology of chronic rheumatism. Atlas of standard radiographs of arthritis. Philadelphia: FA Davis; Lakka TA, Venalainen JM, Rauramaa R, Salonen R, Tuomilehto J, Salonen JT. Relation of leisure-time physical activity and cardiorespiratory fitness to the risk of acute myocardial infarction. N Engl J Med 1994;330: Makela M, Heliovaara M, Sievers K, Knekt P, Maatela J, Aromaa A. Musculoskeletal disorders as determinants of disability in Finns aged 30 years or more. J Clin Epidemiol 1993;46: Bellamy N, Buchanan WW, Goldsmith CH, Campbell J, Stitt LW. Validation study of WOMAC: a health status instrument for measuring clinically important patient relevant outcomes to antirheumatic drug therapy in patients with osteoarthritis of the hip or knee. J Rheumatol 1988;15: