Although exercises to strengthen the quadriceps may relieve joint pain in persons with osteoarthritis of the knee [2-6], the role of periarticular muscle weakness in the pathogenesis of joint pain and disability in these persons is poorly understood. The basis for the beneficial effect of strengthening exercises is unclear, and the duration of the improvement has not been studied. Furthermore, the possibility that muscle weakness is an etiologic factor underlying the pathologic changes of osteoarthritis has seldom been considered. Elucidation of the role of muscle weakness in osteoarthritis is particularly important given our growing understanding of safe and effective methods for increasing strength in elderly persons [7, 8].

A substantial proportion of persons who have radiographic evidence of osteoarthritis of the knee have no joint pain [9]. Because asymptomatic persons with radiographic changes seldom seek medical attention for osteoarthritis, muscle weakness has not been studied previously in this group. Thus, it is not known whether quadriceps weakness precedes or follows joint pain or (if it follows joint pain) whether it is mediated by disuse atrophy or by physiologic mechanisms that may inhibit muscle contraction [10]. To address this issue, we studied the relation among lower-extremity muscle strength, lower-extremity lean tissue mass, and osteoarthritis of the knee in men and women 65 years of age and older.

Methods

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Study Group

To obtain a sample of elderly persons living in the community, we conducted brief telephone interviews with residents of households in central Indiana. Potential participants were selected through modified random-digit dialing to increase the sampled proportion of persons 65 years of age and older. Persons were eligible if they met the minimal criteria for participation: They were willing and able to provide informed consent and to undergo the necessary strength assessments and other evaluations. Persons were excluded if they had had amputations of both lower extremities, had undergone total knee arthroplasty, or had recently had a cerebrovascular accident or myocardial infarction. A total of 462 persons (approximately 55% of all who were eligible) agreed to participate and completed the following evaluations.

Evaluations

Radiography of the Knee

Standing anteroposterior and lateral radiographs of both knees of each study participant were obtained, and the severity of osteoarthritis in the tibiofemoral compartment was graded by a musculoskeletal radiologist according to the criteria of Kellgren and Lawrence. Similar criteria, based on the presence of osteophytes and joint space narrowing, were used for the patellofemoral compartment [11]. The radiologist was blinded to the clinical status and characteristics of all patients. A participant had to have a Kellgren and Lawrence grade of 2 or more in either knee to be classified as having osteoarthritis.

Knee Pain and Function

The Western Ontario and McMaster Universities Arthritis Index was used to evaluate knee pain and function [12]. This index assesses the severity of knee pain during 5 activities or situations (walking on a flat surface, going up or down stairs, at night while in bed, sitting or lying, and standing upright) and the severity of impairment of lower-extremity function during 17 activities. Pain and functional impairment were assessed in each knee separately. Responses to each question about the severity of knee pain and level of impairment were recorded on a categorical scale as none, mild, moderate, severe, or extreme. Each category was assigned a corresponding numeric score from 1 to 5 (5 = extreme). Hence, the range on the pain scale was 5 to 25 and the range on the physical impairment scale was 17 to 85 (85 = greatest functional limitation). For the purposes of analysis, participants who rated the severity of their knee pain as moderate or greater (3) with any of the 5 activities on more than half of the days in the month preceding the evaluation were considered to have knee pain. Thus, pain in the more distant past that had resolved was not included.

Participants were also questioned about current and previous regular (5 times per week) or occasional use of over-the-counter and prescription analgesics and nonsteroidal anti-inflammatory drugs (NSAIDs) in the past year.

Lower-Extremity Muscle Strength

The strength of each leg was evaluated by using an isokinetic dynamometer (KIN-COM 500H, Chattecx Corp., Hixson, Tennessee). Peak torque was recorded in both the concentric (contractions during muscle shortening) and eccentric (contractions during muscle lengthening) modes. Participants were allowed several submaximal or maximal practice efforts to familiarize themselves with the operation of the dynamometer. Once formal testing began, the best of three maximal efforts was recorded for flexion and extension at both 60 degrees per second and 120 degrees per second. Aborted efforts were repeated in order to obtain the best possible representation of strength for each participant. Concentric and eccentric testing yielded similar results, but because of greater variability in eccentric testing, only the concentric test results are shown.

Lower-Extremity Lean Tissue Mass

Total-body dual-energy x-ray absorptiometry was done in all participants by using a Lunar-DPX-L instrument (Lunar Corp., Madison, Wisconsin). Results were analyzed for total and regional body composition, including body fat, mineral, and lean components (lean components were components other than fat or mineral). The right and left lower extremities were analyzed separately. The lower extremity was defined as all tissue below a diagonal line drawn outward and upward from the groin area through the femoral neck.

Statistical Analysis

Participants were divided into four groups on the basis of presence or absence of radiographic evidence of osteoarthritis of the knee and presence or absence of knee pain, as defined above. Men and women were compared by using the t-test. Comparisons of Arthritis Index pain and functional impairment scores were done by using nonparametric approaches. For analyses of continuous data involving more than two groups of participants (for example, osteoarthritis with or without knee pain), analysis of variance was used to determine whether an overall difference was present. The Fisher protected least-significant-difference procedure was used for pairwise comparisons. Comparisons within participants (for example, comparison of the two legs in a person with unilateral osteoarthritis of the knee) were done by using paired t-tests. Regression models were constructed with the generalized estimating equations approach of Zeger and Liang [13]. This approach inflates the standard errors to adjust for correlations in both independent variables (such as strength) and dependent variables (such as radiographic grade) within participants. Statistically significant differences (P < 0.05) in the above analyses are specifically noted below.

Results

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The characteristics of the 462 men and women in the cohort are shown in Table 1. As expected, men were taller, were heavier, and had greater lower-extremity strength and lean tissue mass in the lower extremities compared with women (P < 0.001 for all comparisons).

One hundred forty-five participants (31%; 33% of the women and 30% of the men) had radiographic evidence of osteoarthritis involving the tibiofemoral compartment, the patellofemoral compartment, or both. In 62 participants (43%), the radiographic changes were unilateral.

Table 2 shows the association between osteoarthritis and obesity [14-16]. Women in the cohort who had osteoarthritis were approximately 15% heavier than women with normal radiographs and no knee pain. Men with osteoarthritis were also slightly heavier than men without osteoarthritis.

Among those with radiographic evidence of tibiofemoral osteoarthritis, women were slightly more likely than men to report knee pain (P = 0.10; Table 3).

Table 2 also shows the mean summed and the distribution of scores for left knee pain and functional impairment (data for the right knee were similar). Among men and women with radiographic evidence of osteoarthritis who reported having knee pain, the mean summed pain score for the knee with osteoarthritis was approximately 12 (median score, 2 of 5). In comparison, the mean pain score of participants who reported knee pain but did not have radiographic evidence of osteoarthritis in the painful knee was approximately 10 (median score, 2 of 5)-only slightly lower than the mean pain score of participants with radiographic changes. Consistent with their relatively low pain scores, these community-dwelling participants with osteoarthritis reported moderately low use of NSAIDs (Table 4).

Arthritis Index scores for functional impairment paralleled those for pain (Table 2). Participants with osteoarthritis had the greatest functional impairment (P < 0.001 for the comparison with patients who did not have pain or radiographic evidence of osteoarthritis). Functional impairment in participants who had pain but no radiographic evidence of osteoarthritis also differed (P < 0.001) from that in participants with no pain and no osteoarthritis but did not differ from that in participants with osteoarthritis (Table 2).

Among the small number of participants who reported knee pain, those with isolated patellofemoral disease had lower mean Arthritis Index pain and functional impairment scores than did those with isolated tibiofemoral osteoarthritis or combined tibiofemoral and patellofemoral osteoarthritis (data not shown).

Table 5 shows the values for peak torque (that is, strength) in extension and flexion at 60 degrees per second in relation to the presence of knee pain and radiographic evidence of osteoarthritis. The Figure 1 also shows the data on leg strength for participants, stratified according to radiographic evidence of osteoarthritis and knee pain. Women with osteoarthritis were between 4.7 (no pain) and 8.5 (pain present) lb-ft weaker in left knee extension than were asymptomatic women with normal knees (Table 5 and Figure 1). Only men with symptomatic osteoarthritis showed similar deficits in strength. Right and left legs showed similar patterns. In general, men and women with symptomatic osteoarthritis involving both the tibiofemoral and patellofemoral compartments had the greatest quadriceps weakness (Figure 1), averaging 12 lb-ft deficits (across both legs) in extensor strength compared with participants with no osteoarthritis. However, the small size of this group (12 women and 10 men) limits the statistical power of comparisons with other subgroups that have osteoarthritis.

View larger version (20K): [in this window] [in a new window]   Figure 1. Left leg strength, measured as peak extensor torque at 60 degrees per second, related to sex, topographic localization of radiographic changes of osteoarthritis, and the presence of recent knee pain. The numbers at the top of each bar represent the mean peak torcue, and the numbers in parertheses represent numbers of participants. Strength was generally greater in the right than in the left leg, but the magnitude of the differences in right leg strength among participants was similar to the magnitude of the differences n left leg strength. OA = osteoarthritis; PF = patellofemoral: TF = tibiofemoral.

Although the number of participants with isolated patellofemoral osteoarthritis was small (19 women and 13 men), patellofemoral osteoarthritis alone was not associated with a decrease in leg extensor strength in most cases (data not shown).

Notably, leg weakness among participants with radiographic evidence of osteoarthritis was seen only in extension (Table 5); differences in knee flexor strength among both men and women with osteoarthritis, relative to men and women without pain or radiographic evidence of osteoarthritis, were small (<1 lb-ft) and not statistically significant (P > 0.14). When expressed as a ratio of strength to body weight, the deficits in extensor strength among participants with osteoarthritis were approximately 20% (P < 0.01 by analysis of variance for men and women) in comparison with those in participants without radiographic changes (data not shown).

Furthermore, the lesser leg-extensor strength in women with symptomatic osteoarthritis occurred even though these women had significantly greater lower-extremity lean mass than women with normal radiographs and no knee pain (lean mass, 7.4 compared with 6.5 kg) (Table 5). Similarly, the lower-extremity lean mass of men with osteoarthritis, regardless of the presence of knee pain, was similar to that of men who did not have pain or radiographic evidence of osteoarthritis.

In 58 participants, tibiofemoral osteoarthritis of the knee was unilateral. Although this sample is small, the between-leg differences in strength seen in this subset were consistent with those seen for the entire cohort. In men, the affected leg was 5.2 lb-ft (95% CI, 0.3 to 10.1 lb-ft) weaker with tibiofemoral disease and 10.2 lb-ft (CI, 3.0 to 17.4 lb-ft) weaker with patellofemoral disease (Table 6). Patterns in women were similar but not statistically significant.

Because the prevalence of osteoarthritis increases and strength declines with increasing age, we modeled the presence of osteoarthritis (radiographic changes regardless of pain and radiographic changes plus knee pain) as a function of sex, weight, age, and lower-extremity strength (Table 7). Each 10 lb-ft increase in knee-extension strength was associated with 20% lower odds for radiographic osteoarthritis (radiographic changes with or without symptoms) and 29% lower odds for symptomatic osteoarthritis. In other words, relatively small increases in strength ( –19% of the mean for men and +27% of the mean for women) would be predicted to result in 20% to 30% decreases in the odds for having osteoarthritis.

Discussion

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Examining community-based participants rather than clinic patients with osteoarthritis gave us an opportunity to examine the association between strength and osteoarthritis in persons who had radiographic evidence of osteoarthritis but no knee pain. Consistent with previous observations in clinic populations [7-11, 17], lower-extremity weakness in our population-based sample was greater among participants with radiographic evidence of osteoarthritis than among participants with normal radiographs (Table 5). This weakness in extensor strength, which was independent of the effects of age, sex, and body weight (Table 7), averaged about 0.5 SD (Table 5 and Figure 1) in comparison with the strength values for normal participants who had neither knee pain nor radiographic changes. Notably, among women with isolated tibiofemoral osteoarthritis, extensor weakness was present even among those without knee pain (Figure 1). Furthermore, weakness did not involve the hamstrings but was largely confined to the quadriceps, suggesting that disuse atrophy was not primarily responsible. To further examine the possibility that atrophy was the basis for the observed quadriceps weakness, lean tissue mass in the lower extremities was measured by using dual-energy x-ray absorptiometry. The precision of this method is high [18, 19]. The lean tissue mass of the involved lower extremity of participants with osteoarthritis was similar to or greater than that of participants without osteoarthritis (Table 5). This finding was not unanticipated; it was previously shown that fat-free mass in obese persons is increased [20], consistent with the hypertrophy of muscles required to carry the increased load. Thus, participants with osteoarthritis in our study generated less force with muscle mass equivalent to or greater than that in participants without osteoarthritis.

After adjustment for body weight, age, and sex, lesser quadriceps strength remained strongly predictive of both radiographic and symptomatic osteoarthritis of the knee (Table 7). Because persons with osteoarthritis tend to be obese [19-21] (Table 2), the 15% to 25% strength deficit in our participants with osteoarthritis was even more pronounced when it was considered in relation to body weight.

Although little is known about why quadriceps weakness develops in persons with osteoarthritis, persons with osteoarthritis of the knee who are unable to effect a maximal voluntary contraction of the quadriceps have been described [15]. This phenomenon, arthrogenous muscle inhibition, has been attributed to altered afferent input from the diseased joint and consequent reduction in efferent motor neuron stimulation of the quadriceps [21]. Whether arthrogenous muscle inhibition is a precursor of quadriceps atrophy remains to be determined. In any event, our results are consistent with the possibility that quadriceps weakness precedes, and may be of pathogenetic importance in, the development of knee pain and disability. In addition, because quadriceps action serves as a brake, retarding the rate of descent of the leg at the end of the swing phase of gait [5], quadriceps weakness could accelerate damage to articular cartilage in the knee. Consistent with this possibility, experimental paralysis of the quadriceps led to a marked increase in ankle velocity immediately before heel strike, with an increase in the ground reaction loading rate [22]. These data raise the possibility that weakness may be etiologically related to the initiation, the progression, or both, of pathologic changes in some persons with osteoarthritis of the knee.

As Table 2 shows, Arthritis Index scores were similar in participants who reported recent pain, whether osteoarthritis was present or not. Undoubtedly, some participants who had pain but no osteoarthritis might have been classified as having osteoarthritis if clinical criteria [23] had been used; others are likely to have had soft tissue rheumatism or some other definable medical or orthopedic condition affecting the lower extremity. However, extensor strength among patients who had knee pain but normal knee radiographs was nearly as great as that in the participants who had no knee pain and normal radiographs, suggesting that undiagnosed osteoarthritis was not very common in this group. Some misclassification, however, is likely to have occurred.

The low use of NSAIDs (Table 3) provides additional indirect evidence of the relatively mild level of joint pain among persons with osteoarthritis of the knee. Neither aspirin use nor NSAID use was statistically significantly greater among participants with osteoarthritis who reported recent knee pain than it was among those without knee pain. Insofar as primary care physicians and rheumatologists commonly prescribe NSAIDs for patients with symptomatic osteoarthritis of the knee [24], the low level of prescription NSAID use in our cohort probably suggests low utilization of physician services for this problem. It is of interest that the mean Arthritis Index pain score of our participants with osteoarthritis and knee pain was similar to that reported by Bellamy and colleagues [12], who observed a mean Arthritis Index pain score of 10.3 for persons being enrolled in a drug trial.

Both men and women with the most extensive radiographic osteoarthritis (Kellgren and Lawrence grade 2) involving both the tibiofemoral and patellofemoral compartments were weaker than those in the other subgroups (Figure 1). Among participants with unilateral osteoarthritis, the difference in strength between unaffected and affected limbs was smaller in women than in men (0.8. lb-ft compared with 5.2 lb-ft for tibiofemoral osteoarthritis; 0.6 lb-ft compared with 10.2 lb-ft for patellofemoral osteoarthritis) (Table 6). Others have reported that osteoarthritis of the knee in women older than 65 years of age is predominantly bilateral, whereas osteoarthritis of the knee in men in this age group is more likely to be unilateral, perhaps because of previous joint trauma [25]. However, we did not observe significant differences between the sexes in the distribution of unilateral and bilateral disease (Table 6).

Considerable attention has recently been focused on the patellofemoral compartment as an important cause of pain and disability in persons with osteoarthritis of the knee. McAlindon and colleagues [26] found that isolated symptomatic patellofemoral osteoarthritis was more likely than medial compartment disease to be associated with disability. Our results contrast with those findings: We found that isolated patellofemoral osteoarthritis was associated with better function than was tibiofemoral osteoarthritis. Our results are consistent with those recently reported by Sharma and coworkers [27], who analyzed 172 persons with osteoarthritis of the knee and found that 1) mixed tibiofemoral and patellofemoral compartment disease had a greater effect on function, as measured by the Arthritis Index, than tibiofemoral disease alone, and 2) in persons with mixed disease, tibiofemoral, but not patellofemoral joint space narrowing, was related to impairment of function.

In conclusion, our observations indicate that quadriceps weakness exists in some persons who have osteoarthritis in the absence of either detectable muscle atrophy or joint pain. They suggest that knee-extensor weakness may be a risk factor for the initiation and progression of damage to articular cartilage and other tissues in the knee with osteoarthritis. Others have observed periarticular muscle weakness among clinic patients with symptomatic osteoarthritis of the knee, and short-term clinical trials have shown improvement in knee pain and function in such patients after exercise interventions aimed at increasing leg strength [7-11, 27]. Maintaining increased strength after termination of the intervention is difficult, however, and alleviation of symptoms can be lost rapidly with cessation of training [7]. Whether exercises to strengthen quadriceps can prevent the development or progression of pathologic changes of osteoarthritis or decrease the risk for joint pain or disability requires evaluation in a randomized, placebo-controlled trial.