Quadriceps activation failure as a moderator of the relationship between quadriceps strength and physical function in individuals with knee osteoarthritis

Authors


Abstract

Objective

To determine if quadriceps activation failure (QAF) moderates the relationship between quadriceps strength and physical function in individuals with knee osteoarthritis (OA).

Methods

Quadriceps strength and QAF were measured in 105 subjects (80 females) with radiographically confirmed knee OA using a burst-superimposition maximum voluntary isometric quadriceps torque test procedure. Subjects performed the Get Up and Go test as a physical performance measure of function and completed the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) as a self-report measure of function. A principal component analysis was performed to combine the Get Up and Go score and the WOMAC subscores into a single function score. Hierarchical regression analysis was performed to examine the ability of 3 models to predict physical function (strength = function; strength + QAF = function; strength + QAF + [strength × QAF] = function). Partial F tests were used to compare differences in R2 values between each model.

Results

Each model independently predicted the principal component score for function. Adding the strength × QAF interaction term with strength to the model resulted in the highest prediction of function. The strength × QAF interaction indicated that subjects with lower levels of quadriceps strength and higher levels of QAF had lower levels of function than those with comparable levels of weakness but low levels of QAF.

Conclusion

The magnitude of QAF serves to moderate the relationship between quadriceps strength and physical function. Physical function may be more severely affected by weakness of the quadriceps muscles in individuals with knee OA who have higher degrees of QAF than those who may have quadriceps weakness, but do not have QAF.

INTRODUCTION

Osteoarthritis (OA) of the knee is the most prevalent type of OA in the United States (1) and it has been reported that the presence of knee OA contributes substantially to functional limitations in performance of such weight-bearing tasks as walking, stair climbing, housekeeping, and carrying bundles (2). It has been well documented that patients with knee OA have significantly greater deficits in quadriceps strength compared with age- and sex-matched controls (3–6). Because the quadriceps muscles play a significant role in attenuating loads across the knee joint, it is believed that weakness in the quadriceps muscles reduces their capacity to protect the knee, predisposing the knee to greater physical stress and perhaps extended structural damage (6). Quadriceps weakness has been found to be a risk factor for knee pain and may also be associated with deficits in balance and postural sway in individuals with knee OA (3, 7, 8). Some studies have reported that quadriceps weakness is associated with poorer self-report ratings of function and disability (4, 9) and may also be a predictor in the rate of decline in physical function over time for individuals with knee OA (10).

The source of quadriceps femoris weakness in patients with knee OA is unclear. Pain and atrophy resulting from reduced activity are often implicated as causes of quadriceps weakness, however, Slemenda et al (11), have provided evidence that some patients with knee OA exhibit quadriceps weakness even in the absence of pain or atrophy. This finding suggests that the presence of pain and disuse atrophy alone may not explain the associated quadriceps weakness in knee OA, and that there may be other mechanisms that contribute to quadriceps weakness in patients with knee OA. Hurley and Newham (12) have demonstrated that some patients with knee OA exhibit an inability to fully activate the quadriceps muscles, a condition that we will refer to as quadriceps activation failure (QAF). The presence of QAF was determined by decreased voluntary maximum isometric quadriceps torque output compared with the torque output produced during superimposition of an electrical stimulus on a maximum voluntary isometric quadriceps contraction. Although investigators have associated QAF with the presence of joint effusion in patients with knee injuries (13–16), some patients with knee OA demonstrated QAF in the absence of significant joint effusion (4). Hurley et al (4) suggested that degenerative changes to joint structures in knee OA may result in altered sensory information from joint mechanoreceptors that, in turn, may reduce the ability to activate the quadriceps femoris muscles.

Individuals with knee OA have been found to exhibit greater QAF compared with age- and sex-matched control subjects (4, 12, 17). The presence of QAF has been associated with greater impairment in quadriceps strength and poorer scores on physical performance and self-report measures of physical function in individuals with knee OA (4). It may be possible that the relationship between quadriceps strength and physical function is amplified when individuals with knee OA exhibit increasing amounts of QAF. If this were true, then QAF would be considered a moderator of the relationship between quadriceps strength and physical function. A moderator is a qualitative or quantitative variable that affects either the direction or strength of the relationship between an independent or predictor variable (e.g., quadriceps strength) and a dependent or criterion variable (e.g., physical function) (18).

The function of a variable as a moderator can be confirmed if the interaction of the predictor variable (e.g., quadriceps strength) and the moderator variable (e.g., QAF) improves the prediction of the independent variable (e.g., physical function) (18). A potential implication of this finding would be that QAF is a factor that may need to be specifically addressed in rehabilitation to optimize improvements in both quadriceps strength and physical function for individuals with knee OA.

The aim of this study was to determine if QAF functions as a moderator of the relationship between quadriceps strength and physical function in individuals with knee OA. We hypothesized that if QAF moderates the relationship between quadriceps strength and physical function, then the addition of the interaction of quadriceps strength and QAF would improve the prediction of physical function over the prediction of physical function based upon quadriceps strength alone.

PATIENTS AND METHODS

Patients.

Patients included 105 individuals (80 women and 25 men) who had been diagnosed by their physician as having OA of the knee (tibiofemoral or patellofemoral involvement). Subjects were included in the study if they were 45 years of age or older, had knee radiographs performed within the past 12 months, met the 1986 American College of Rheumatology (ACR) clinical and radiographic criteria for knee OA (19), and had grade II or greater Kellgren and Lawrence radiographic changes (20). The 1986 ACR criteria for diagnosis of knee OA include knee pain with osteophytes and at least 1 of the following: age ≥50 years, morning stiffness <30 minutes, or crepitus with active motion of the knee, such as when squatting while bearing weight (19). Subjects were excluded from the study if they 1) had limitations in knee motion that prevented them from comfortably positioning their knee for the quadriceps torque test, 2) had undergone total knee arthroplasty, 3) complained of pain in other lower extremity joints that affected their ability to perform activities of daily living, 4) exhibited uncontrolled hypertension, 5) had a history of cardiovascular disease, or 6) had other preexisting conditions that would place them at risk for injury to the extensor mechanism during quadriceps torque testing (e.g., a history of patellar tendon autograft anterior cruciate ligament reconstruction, patellar or quadriceps tendon rupture, patellar fracture, prolonged corticosteroid use, or steroid injection of the patellar or quadriceps tendons). Subject demographic information is provided in Table 1.

Table 1. Subject characteristics, n = 105*
CharacteristicValue
  • *

    Data are presented as no. (%) unless otherwise indicated. Age, years, mean ± SD (range) 62.0 ± 9.6 (46–84). Body mass index, kg/cm2, mean ± SD (range) 0.33 ± 0.06 (0.18–0.53).

  • Kellgren and Lawrence grades are for the most symptomatic knee. Medial and lateral compartments were evaluated using an anteroposterior radiographic view. The patellofemoral compartment was evaluated using lateral and merchant radiographic views. Bilateral disease was defined as having grade II or greater radiographic changes in both knees.

  • Years with knee osteoarthritis (OA) was defined as the number of years from the time that subjects were first given the diagnosis of OA by their physicians.

Female80 (76.0)
Employment 
 Full time regular duty32 (30.4)
 Part time regular duty13 (12.4)
 Light duty or part time modified duty6 (5.7)
 Unable to work or retired due to health status7 (6.7)
 Retired31 (29.5)
 Homemaker15 (14.3)
 Unemployed1 (1.0)
Work activity 
 Mostly sedentary37 (35.2)
 Somewhat sedentary with substantial walking required18 (17.1)
 Moderately active: walking, some lifting and carrying42 (40.0)
 Demanding physical activity, heavy lifting and carrying8 (7.6)
Radiographic knee OA 
 Grade II27 (26)
 Grade III35 (33)
 Grade IV43 (41)
 Medial compartment95 (90)
 Lateral compartment44 (42)
 Patellofemoral compartment51 (49)
Bilateral knee OA68 (64.8)
Years with knee OA 
 <15 (4.8)
 1–213 (12.4)
 3–537 (35.2)
 5–1036 (34.3)
 >1014 (13.3)
Prior knee injury or surgery34 (32.4)
Medications 
 Over the counter analgesics48 (45.7)
 Prescription analgesics5 (4.8)
 Over the counter nonsteroidal anti-inflammatory drugs24 (22.9)
 Prescription nonsteroidal antiinflammatory drugs66 (62.9)
 Arthritis creams16 (15.2)
 Nonarthritic medications80 (76.2)

Patients were recruited from physician's offices of the University of Pittsburgh Medical Center (UPMC) Arthritis Network, the UPMC Arthritis Network Registry, and from physical therapy clinics of the Centers for Rehabilitation Services of the UPMC Health System. All subjects signed an informed consent form approved by the University of Pittsburgh Institutional Review Board prior to participation in the study.

Basic testing procedure.

Data for each subject were collected during 1 testing session that lasted approximately 1.5 hours. During the session, the subjects first completed a demographic and health history questionnaire and a self-report measure of function. Then, a physical examination was performed to determine range of motion and the presence of effusion of the knee. Following the examination, physical performance testing procedures were performed.

Measurement of QAF and quadriceps torque output.

The magnitude of QAF as well as quadriceps muscle strength was measured using a burst-superimposition maximum isometric quadriceps torque test. This procedure has been shown to yield reliable quadriceps femoris torque measurements by other investigators (21) and in our own laboratory (intraclass correlation coefficients [ICCs] for intratester reliability [between 1 and 3 days] = 0.97 and intertester reliability [same day] = 0.82). Because most subjects had bilateral knee involvement, an involved-to-uninvolved limb comparison was not possible. Therefore, we elected to test the limb that subjects reported as being the most symptomatic limb with regard to pain and functional limitation.

Patients were seated on an isokinetic dynamometer (Biodex System 3 Pro, Shirley, NY) with the dynamometer force-sensing arm secured to the ankle. The knee being tested was positioned in 60° of flexion, with the lateral femoral epicondyle aligned with the dynamometer's axis of rotation. The skin in the area of electrode placement sites over the anterior thigh was cleansed with rubbing alcohol, and electrodes were then placed proximally over the vastus lateralis muscle belly and distally over the vastus medialis muscle belly. A thigh strap, waist strap, and 2 chest straps were then secured to stabilize the patient in the dynamometer chair. Once the patient was prepared for testing, we employed a process of potentiating the quadriceps muscles to maximize the subject's ability to produce maximum torque output (22). In addition, this process familiarized the subjects with both the electrical stimulus to be used during testing, and the maximum voluntary isometric torque test procedure, which would help minimize the potential for learning effects on the test results.

During the first step in this process, subjects practiced producing voluntary isometric quadriceps contractions against the force-sensing arm of the dynamometer at 50%, 75%, and 100% effort. Following the voluntary practice trials, subjects received 3 successive trains of electrical stimulation (pulse duration = 600 μsec, pulse interval = 10 msec, train duration = 100 msec), separated by 30-second time intervals, applied to the resting muscle at amplitudes of 40V, 60V, and 100V.

Following the series of electrical stimuli, formal measurements of maximum voluntary isometric quadriceps strength and QAF were initiated. Subjects were asked to exert as much force as possible while extending the knee against the fixed force-sensing arm of the dynamometer and the train of electrical stimuli (amplitude = 100V, pulse duration = 600 μsec, pulse interval = 10 msec, train duration = 100 msec) was applied during the contraction to determine the extent of muscle activation failure. A torque target line was displayed on the computer monitor to provide subjects with visual feedback in an effort to maximize their ability to produce maximum torque output during the test. The torque target was placed at a torque level slightly greater than the peak torque produced during the practice maximum voluntary isometric contraction. If subjects exceeded this torque target during a given trial, the target was reset at a higher level for the next trial. The test was repeated for up to 4 trials. It has been demonstrated that individuals should achieve maximum muscle activation during a maximum voluntary isometric contraction within 4 trials (23).

The magnitude of QAF was calculated using the quadriceps central activation ratio (CAR), which is the ratio of the highest maximum voluntary torque produced during the 4 trials prior to delivery of the electrical stimulus divided by the highest total torque of the 4 trials produced when the electrical stimulus was superimposed on the maximum voluntary contraction (24). The magnitude of QAF is equivalent to 1 CAR. Maximum voluntary isometric quadriceps torque output was expressed as a ratio of peak isometric quadriceps torque output obtained prior to application of the stimulus divided by the subject's body mass index.

Get Up and Go test.

The Get Up and Go test was used as a physical performance measure of function. The test was performed as described by Hurley et al (4). To perform the test, subjects were seated on a standard-height chair with armrests. On the command “go,” subjects stood up and walked along a level, unobstructed, corridor as fast as possible. A stopwatch was used to measure the length of time it took for the subject to stand up and walk 15 meters. We examined intratester and intertester reliability of the Get Up and Go test, and have demonstrated good intratester (ICC = 0.95) and intertester reliability (ICC = 0.98) for this test at our facility. A longer time to complete the Get Up and Go test represents greater limitations in function.

Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC).

The WOMAC was used as a self-report measure of function. The WOMAC is a disease-specific measure of pain, stiffness, and physical function for individuals with knee OA. The WOMAC includes 5 items related to pain, 2 items related to stiffness, and 17 items related to physical function. Each item is scored on a 5-point Likert scale. Reliability and validity of the WOMAC have been established (25). Higher scores on the WOMAC represent greater limitations in function.

Other factors potentially associated with QAF.

We recorded a number of other factors that could potentially be associated with QAF. Demographic factors included age, sex, body mass index, and number of years with a diagnosis of knee OA. Clinical factors included knee pain during the burst-superimposition testing procedure, the presence or absence of a knee joint effusion, the severity of radiographic knee OA, and medication use. Knee pain during the burst-superimposition test was measured using a 0–10 numeric pain scale, with 0 representing no pain and 10 representing the worst pain imaginable.

The presence or absence of a knee joint effusion was determined using the patellar ballotment and bulge tests described by Magee (26). During the patellar ballotment test, the examiner attempts to entrap fluid around the patellofemoral joint with the both hands by pushing down on the soft tissues superiorly and inferiorly to the patella. The examiner then uses an index finger to push down on the patella. Normally the examiner should be able to approximate the patella with the femur. If effusion is present, the examiner will have difficulty approximating the patella to the femur and the patella will feel as if it is floating on top of the femur. If small to moderate amounts of effusion are present, the ballotment test may yield a false-negative finding. The bulge test may be more sensitive in detecting effusion in this instance. During the bulge test, the examiner brushes the skin along the medial aspect of the knee with the hand from just inferior to the joint line to the suprapatellar pouch 2 or 3 times. With the opposite hand, the examiner brushes down the lateral side of the patella. If effusion is present, the examiner will observe a bulging of fluid on the medial side of the knee. We used both tests to determine if an effusion was present or absent. If either of these tests was positive, an effusion was considered to be present. If both tests were negative, an effusion was considered to be absent. The reliability of the patellar ballotment test and bulge test for identifying joint effusion has not been reported in the literature.

The severity of radiographic knee OA was rated by an experienced rheumatologist, using the method described by Kellgren and Lawrence (20). Use of medication was determined by the information collected on the demographic and health history questionnaire.

Statistical analysis.

Pearson correlation coefficients were calculated to determine the relationship of age, body mass index, pain ratings during the burst-superimposition test, and the number of years with the diagnosis of knee OA with QAF and quadriceps strength. Point biserial correlations were calculated to determine the associations between sex, the presence of joint effusion, and medication use with QAF and quadriceps strength. The Pearson and biserial correlation coefficients were converted to coefficients of determination (R2) to determine the strength of association between the aforementioned variables and QAF and quadriceps strength. Eta squared was calculated to determine the strength of association of the severity of radiographic knee OA with QAF and quadriceps strength. The level of significance was set at 0.05.

Hierarchical linear regression was performed to test the hypothesis that QAF is a moderator of the relationship between quadriceps strength and physical function in individuals with knee OA. Prior to performing the regression analysis, a principal component analysis was used to combine the WOMAC stiffness, pain, and physical function scores as well as the Get Up and Go test score into a single principal component score for physical function. Several authors suggested that because the relationship between performance-based and self reported measures of function is at most moderate, these measures may be measuring different aspects of the construct of physical function (27–30). Because the WOMAC stiffness, pain, and physical function scores were all moderately correlated with the Get Up and Go test scores (r ranged from 0.30 to 0.39, P < 0.01) in our sample, we decided to combine the self report and physical performance measures of function to provide a more comprehensive measure of function as well as to provide a more parsimonious method to study the relationship of function with quadriceps strength and activation failure.

The Get Up and Go test score and the 3 components of the WOMAC (stiffness, pain, and physical function scores) were entered into the principal component analysis. The eigenvalue >1 rule was used to extract the principal components (31). In this study, only 1 principal component was extracted, which implied that there was a single dimension underlying the 4 original variables.

The principal component analysis allowed us to combine the 4 original variables into a single principal component score of physical function (PCPF) for each subject. This was accomplished by transforming each subject's score on each of the 4 measures of physical function to a Z score. The Z score for each variable was then multiplied by the principal component score coefficient for that variable. The resulting products were then summed to create a PCPF for each subject. The PCPFs were normalized to have a mean of 0 and a standard deviation of 1. The PCPF for each subject was multiplied by –1.0 so that higher PCPF values represented higher levels of physical function. An example of this calculation is provided in Table 2.

Table 2. Example calculation of the principal component score for physical function (PCPF)*
VariableComponent score coefficientZ scoreComponent score coefficient × Z score
  • *

    WOMAC = Western Ontario and McMaster Universities Osteoarthritis Index. PCPF = [(−0.3797) + (−0.2667) + (−0.5794) + (−0.2043)] × (−1.0) = 1.4301.

WOMAC pain0.336−1.13008−0.3797
WOMAC stiffness0.320−0.83347−0.2667
WOMAC physical function0.345−1.67944−0.5794
Get Up and Go time0.211−0.96809−0.2043

During the hierarchical regression analysis, we tested 3 models to predict the PCPF. In the first model, the PCPF was regressed on quadriceps strength (quadriceps strength = PCPF). In the second model, the PCPF was regressed on both quadriceps strength and QAF (quadriceps strength + QAF = PCPF). Finally in the third model, the PCPF was regressed on quadriceps strength, QAF, and the interaction between quadriceps strength and QAF (quadriceps strength + QAF + [quadriceps strength × QAF]). Partial F tests were used to determine if there were significant differences between the 3 models in predicting the PCPF. The level of significance for testing of the regression models was 0.05.

Post-hoc testing to describe the direction of a significant QAF moderating effect was performed using the method of post-hoc probing of moderating effects described by Holmbeck (32). Briefly, simple regression lines were computed representing the association between centered quadriceps strength scores and the PCPF under conditions of high versus low centered QAF scores (see plot in Figure 1). Centering of the quadriceps strength and QAF scores is accomplished by subtracting the sample mean from all subjects' scores on the respective variable, thus producing a revised sample mean of 0 for each variable. Centering the variables is recommended before performing regression analyses to facilitate the testing of simple slopes, and it does not alter the significance of the interaction or alter the values of the simple slopes (32). Regression analyses were used to determine if the slopes of these lines were significantly different from 0, with the level of significance being 0.05.

Figure 1.

Plot of post-hoc probing of the moderating effect of quadriceps activation failure (QAF) on the relationship between strength and physical function. The plot illustrates the 2-way interaction of the regression lines for the relationship between quadriceps strength and physical function as moderated by high versus low levels of QAF. −1 SD = 1 standard deviation below the mean for quadriceps strength and classified as weak; +1 SD = 1 standard deviation above the mean for quadriceps strength and classified as strong; * = slope of the high QAF regression line is significantly different from 0; β = 0.68, P < 0.001.

RESULTS

Factors related to QAF and quadriceps strength.

Age, body mass index, numeric pain ratings during the burst-superimposition test, and the number of years since diagnosis of knee OA were not significantly correlated with QAF. There was a very small but statistically significant association between sex and QAF (R2 = 0.048, P < 0.05), indicating that women tended to exhibit greater QAF than men. There were no significant associations between the presence of joint effusion; the severity of radiographic knee OA; or the use of analgesic, nonsteroidal anitinflammatory, or nonarthritic medications and the magnitude of QAF.

Sex was found to be associated with quadriceps strength (R2 = 0.35, P < 0.01), with women exhibiting lower strength than men. With regard to medications, use of over the counter analgesics was found to be associated with quadriceps strength (R2 = 0.05, P < 0.05), with those subjects who were taking over the counter analgesics exhibiting lower strength than those not taking this medication. There were no significant associations between any of the other categories of medication, age, the presence of joint effusion, or the severity of radiographic knee OA and quadriceps strength.

QAF as a moderator of the relationship between strength and function.

Means, standard deviations, and ranges for quadriceps strength (torque/body mass index), QAF, Get Up and Go test times, and the WOMAC scores are provided in Table 3. The correlation matrix for these variables is provided in Table 4. Quadriceps strength was positively correlated with the PCPF, indicating that reduced quadriceps strength was associated with greater limitations in physical function. Conversely, QAF was negatively correlated with the PCPF, indicating that greater QAF is associated with lower PCPF scores.

Table 3. Means, standard deviations, and ranges for quadriceps strength; QAF; Get Up and Go test times; and WOMAC stiffness, pain, physical function, and total scores*
VariableMean ± SDRange
  • *

    QAF = quadriceps activation failure; WOMAC = Western Ontario and McMaster Universities Osteoarthritis Index.

Quadriceps strength (torque/body mass index)447.6 ± 183.4114.8–977.9
QAF, %3.6 ± 5.00.0–38.0
Get Up and Go Time, seconds11.5 ± 6.15.6–60.0
WOMAC stiffness score (0–8 scale)3.3 ± 1.60.0–8.0
WOMAC pain score (0–20 scale)6.9 ± 3.50.0–17.0
WOMAC physical function score (0–68 scale)22.3 ± 11.91.0–58.0
WOMAC total score (0–96 scale)32.6 ± 15.92.0–82.0
Table 4. Correlation matrix for quadriceps strength; QAF; Get Up and Go times; WOMAC stiffness, pain, physical function and total scores; and the PCPF*
 Quadriceps strength (torque/body mass index)QAFGet Up and Go timesWOMAC stiffnessWOMAC painWOMAC physical functionWOMAC total
  • *

    QAF = quadriceps activation failure; WOMAC = Western Ontario and McMaster Universities Osteoarthritis Index; PCPF = principal component score for physical function.

  • Correlation significant at the 0.01 level (2-tailed).

  • Correlation significant at the 0.05 level (2-tailed).

QAF−0.35      
Get Up and Go times−0.450.58     
WOMAC stiffness−0.230.110.30    
WOMAC pain−0.240.090.350.66   
WOMAC physical function−0.330.200.380.700.77  
WOMAC total−0.320.180.390.770.860.99 
PCPF0.36−0.26−0.56−0.85−0.89−0.91−0.96

Table 5 provides the results of the hierarchical regression analysis. Because sex was found to be associated with QAF and quadriceps strength, and taking over the counter analgesic medication was found to be associated with quadriceps strength, we controlled for the effect of these variables by entering them into the regression analysis first. After controlling for the effects of sex and medication on the PCPF, strength was found to be an independent predictor of function. The addition of QAF to the model did not significantly increase prediction of the model. However, the addition of the strength × QAF interaction term to the model significantly increased prediction of PCPF, as confirmed by the partial F tests (see Table 5). This result indicated that QAF serves as a moderator for the relationship between strength and physical function.

Table 5. Comparison of regression models for predicting the principal component score for physical function (PCPF)*
ModelRR2R2 changedfPartial FP
  • *

    df = degrees of freedom; Med = over the counter analgesic medications; strength = quadriceps strength (torque/body mass index); QAF = quadriceps activation failure; (Strength × QAF) = the interaction of quadriceps strength and QAF.

Sex0.170.030.031, 1032.90.089
Sex + Med0.210.040.011, 1021.60.208
Sex + Med + Strength = PCPF0.370.140.101, 10112.50.001
Sex + Med + Strength + QAF = PCPF0.390.160.021, 1002.10.161
Sex + Med + Strength + QAF + (Strength × QAF) = PCPF0.460.220.061, 997.80.007

Figure 1 provides a plot of the simple regression lines computed for post-hoc probing of the moderating effect of QAF. The post-hoc regression analyses indicated that the slope of the line under conditions of low QAF is not significantly different from 0, suggesting that lower levels of QAF have no significant effect on the relationship between quadriceps strength and the PCPF. In contrast, the slope of the line under conditions of high QAF was found to be significantly different from 0, suggesting that higher levels of QAF have a significant effect on the relationship between quadriceps strength and physical function. According to the plot, at lower levels of quadriceps strength (1 standard deviation below the mean), subjects with higher levels of QAF had lower levels of function than those with comparable levels of weakness but low levels of QAF. Conversely, at higher levels of quadriceps strength (1 standard deviation above the mean), subjects with higher levels of QAF had higher function scores than those with comparable levels of strength but low levels of QAF.

DISCUSSION

Our results indicate that the relationship between quadriceps strength and physical function is moderated by the degree of QAF. When subjects had significantly weak quadriceps muscles combined with higher levels of QAF, they appeared to have greater difficulty with physical function than subjects with comparable levels of quadriceps weakness with little or no QAF (see Figure 1). When subjects had relatively better quadriceps strength combined with higher levels of QAF, they appeared to have better physical function than those of comparable strength with little to no QAF.

We cannot explain why stronger subjects with higher QAF exhibited higher function scores than stronger subjects with low QAF. Stronger subjects did have above-average function scores whether they had higher levels of QAF or not. The implication may be that when subjects with knee OA have relatively good strength, the presence or absence of QAF may not play an important role in affecting physical function. It may be that if they have enough strength to function well, they do not need to learn to activate their quadriceps muscles to any further degree. In contrast, when subjects have significant weakness, the presence of higher levels of QAF may have greater importance with regard to limitations in physical function. Furthermore, it may be possible that larger amounts of QAF combined with greater weakness may limit the degree to which voluntary exercise can restore quadriceps strength and improve physical function in patients with knee OA.

Although QAF has been associated with greater impairment in quadriceps strength and reduced physical function, there is limited information concerning the degree to which QAF may interfere with the recovery of strength and physical function following exercise therapy. In individuals with traumatic knee injuries, a higher degree of QAF prior to rehabilitation was found to limit the recovery of quadriceps strength, even after an intensive leg strengthening program (33). It is believed that in the presence of QAF, the quadriceps muscles may not be able to produce enough muscle tension during volitional exercise to render a beneficial effect from training (33). In individuals with knee OA, there may be a subgroup of patients with weak quadriceps muscles combined with higher degrees of QAF that may not be able to respond favorably to volitional exercise therapy programs. This could explain, in part, the overall modest effects of exercise therapy in restoring quadriceps strength, reducing pain, and improving function in patients with knee OA. Individuals who exhibit relatively large magnitudes of QAF may need specialized treatment interventions designed to improve muscle activation to supplement volitional exercise programs to achieve maximum benefit from rehabilitation (33).

What is not yet clear is how much QAF is required to interfere with the beneficial effects of voluntary strengthening exercises. Few studies have measured changes in QAF, quadriceps strength, and physical function in response to a volitional exercise program in individuals with knee OA (34). In studies that have measured changes in QAF and strength in response to volitional exercise, there appeared to be some reduction in QAF, improvement in quadriceps strength, and improvement in physical function for the exercise groups overall; however, there was no attempt in these studies to determine whether the prerehabilitation magnitude of QAF could predict the degree of improvement in these measures following rehabilitation (34). Establishing the value of QAF that would affect the outcome of exercise therapy may be important in refining rehabilitation programs for individuals with knee OA. Specifically, rehabilitation programs could be tailored to meet the specific needs of the individual patient based on the presence or absence of a clinically meaningful level of pretreatment QAF when patients have significant quadriceps weakness. Those who are weak but exhibit lower values of QAF may only require standard exercise therapy, whereas those who are weak with larger values of QAF may require specialized interventions, such as neuromuscular electrical stimulation or electromyographic biofeedback training, which would address quadriceps activation, in addition to standard exercise therapy. This is an area of future study.

Consistent with the findings of other investigators (4, 7), we found larger magnitudes of QAF to be associated with greater quadriceps weakness in individuals with knee OA. The magnitude of QAF in our sample, however, was substantially lower than that reported by other investigators (4, 7). The mean magnitude of QAF in our sample was 3.6% (range 0–38%) compared with 27.5% reported by Hurley et al (4), and 34% reported by Hassan et al (7). Our sample of individuals with knee OA appeared to be similar in age, severity of knee OA, and level of disability as those in the other 2 studies.

The difference in the mean QAF in our study compared with others may be related to differences in methodology. Although we used a different application of the electrical stimulus compared with Hurley et al (4) and Hassan et al (7), we do not believe the difference in stimulus would explain our results in this case. Hurley et al and Hassan et al used stimuli that produced ∼20–25% of the maximum voluntary torque output when the stimulus was applied to the resting muscle. In our study, the stimulus produced on average 43% of the maximum voluntary torque when applied to the resting muscle. Given that our stimulus produced almost twice the torque of the previous investigators, we believe that our stimulus was strong enough to adequately quantify the magnitude of QAF. Furthermore, because we found similar relationships between QAF, quadriceps strength, and physical function as reported by others, we are confident that we are measuring the same phenomenon. The implication, however, is that the precise magnitude of QAF cannot be directly compared across studies using different stimulus parameters and different testing procedures.

We did not find the presence of joint effusion to be associated with QAF or quadriceps strength in our study. This is in contrast to what has been observed in other patient populations with traumatic knee injuries (13–16). It may be that individuals with knee OA do not exhibit amounts of joint effusion large enough to induce the QAF that might be observed in other patient samples. We did not quantify the amount of joint effusion so we cannot be certain that this is the case.

Complaints of knee pain could also affect measurements of QAF and quadriceps strength. We obtained numeric ratings of knee pain during our testing procedures and did not find this variable to be correlated with our measurements of QAF and quadriceps strength. Complaints of pain at joints other than the knee could also potentially affect measurements of physical function. In our study, we excluded individuals who reported pain at other lower extremity joints that limited their ability to function. Given the age range of our subjects, it is possible that some subjects may have had arthropathies at joints in addition to their knees, but they were asymptomatic. Therefore, we are confident that this was not a significant confounder in our study.

In summary, QAF appears to moderate the relationship between quadriceps strength and physical function. There may be a need to employ adjunct treatments designed to improve muscle activation, concomitant with voluntary strengthening programs for individuals with greater levels of QAF, to improve the overall effectiveness of exercise therapy programs in patients with knee OA. Additional work is needed to determine if the pretraining magnitude of QAF can be used to identify a subgroup of individuals who may have difficulty responding to voluntary strengthening exercises alone. Such individuals may need to be targeted for adjunct interventions (e.g., neuromuscular electrical stimulation or electromyographic biofeedback) that would enhance muscle activation.

Acknowledgements

We would like to acknowledge support from the UPMC Arthritis Network Registry for assistance with subject recruitment for this study.

Ancillary