Knee osteoarthritis (OA) is a leading cause of chronic disability in older persons (1). As defined by Jette et al, disability is the impaired performance of expected socially defined life tasks, in a typical sociocultural and physical environment (2). Physical function limitation, or difficulty with physical tasks and activities, is fundamental to the development of disability in OA. Pain is likely to be a central factor in the physical function limitation of knee OA, both due to its direct effects on function and as a route through which other factors operate. However, pain is not the only source of functional limitation in knee OA (3). In the Framingham study, limited function was more likely to occur in conjunction with moderately severe OA and infrequent pain than with milder OA and frequent pain (4). Identification of factors, in addition to pain, that contribute to poor physical function provides an opportunity to broaden the strategies to prevent disability.
The literature dealing with physical function limitation in knee OA includes a wealth of cross-sectional studies but few longitudinal studies. These published OA studies and/or longitudinal reports not limited to subjects with arthritis have introduced several factors as potential determinants of physical function outcome in knee OA, including obesity, comorbidity, depressive symptoms, low social support, and low levels of physical activity. Self-efficacy, defined by Bandura (5) as the belief in one's capacities to mobilize the internal resources and course of action needed to meet given situational demands, predicted physical function outcome in a longitudinal study of older adults with knee pain (6, 7).
Local impairments of knee function in knee OA may also have some bearing on difficulty with physical tasks and activities. Several local factors influence knee function, including varus-valgus knee stability, by contributing to tibiofemoral congruence and load distribution across the articular surface; hip-knee-ankle alignment, by proportionately dividing load between the medial and lateral compartments; muscle activity, by adding stability, controlling the stop and start of joint motion, and compensating for gravity; and joint proprioception, or the perception of joint position, by providing input to the nervous system to guide periarticular muscle activity. Although these factors may be impaired in some individuals prior to disease development, they also may be made worse by OA (8–10). In the examination of the relationship between the disease itself and limitation of function in knee OA, the disease has been considered globally, using radiographic severity as a surrogate, whereas the impact of specific disease-associated impairments on limitation of function has received little attention.
There is no established approach to define and analyze physical function over time in studies of knee OA. The examination of change in a function measure between baseline and followup is limited by its failure to capture the possibility of a sustained high level of function as a good outcome or a sustained low level of function as a bad outcome. Also, the meaning of small increments of change in a function measure, treated as a continuous variable, is unclear. Ideally, the approach taken to assess outcome should capture an individual's experience over time, and should achieve this in an interpretable way.
Advancing knowledge of factors contributing to a poor physical function outcome will aid in the development of strategies to prevent function limitation and consequential disability. The goal of this prospective study was to identify the factors that predict a poor physical function outcome assessed over 3 years in individuals with knee OA.
- Top of page
- PATIENTS AND METHODS
The likelihood of a poor function outcome as assessed by the WOMAC over 3 years in persons with knee OA was increased by the presence of greater varus-valgus laxity, BMI, and knee pain intensity at baseline and a larger baseline to 18-month increase in pain intensity, and was decreased by better baseline mental health, self-efficacy, and social support and more aerobic exercise. The likelihood of a poor outcome as assessed by chair-stand performance was increased by an older age and greater proprioceptive inaccuracy (approaching significance), and was reduced by greater strength and self-efficacy and more aerobic exercise. The effect of strength was somewhat reduced by adjusting for age, pain, and BMI, and was lost after adjusting for self-efficacy. The WOMAC and chair-stand performance rating identified different factors, supporting the concept that self-report and performance measures each capture unique aspects of functioning and should not be substituted for each other. The change in most risk factors from baseline to 18 months did not predict the outcome over 3 years, possibly reflecting the generally small amount of change between baseline and 18 months.
The level of self-efficacy predicted the outcomes by both the self-report and the performance function measures. Differences in self-efficacy between persons who sustained high function and those who declined in function or sustained low function appeared larger than for any other factor. Our results are consistent with those reported by Rejeski et al, who found, in the Observational Arthritis Study in Seniors (OASIS), that in older persons with knee pain, self-efficacy predicted both the self-reported and stair-climb performance outcomes, after adjusting for pain and strength (7). In the current study, there was similarly no evidence of confounding by either the intensity of pain or strength. In addition, we found no evidence of confounding by mental health status or aerobic exercise.
This study is the first to show evidence of the relationship between greater baseline varus-valgus laxity and increased odds of a poor baseline to 3-year WOMAC function outcome. Both persons who sustained high function and those who improved had lower levels of laxity. Cross-sectional relationships between laxity and function (see ref. 11, which also involves the cohort of the current study), and between symptoms of instability and function (27) have been reported in knee OA. Varus-valgus laxity increased the likelihood of OA after ligament injury (28, 29), was worse in persons with OA (even in their nonarthritic knees) than in elderly controls, and was made worse by aspects of the disease (9). The mechanism of the laxity–function relationship may, in theory, be related to symptoms of pain or instability, the effects of laxity on knee function, or both. We found no evidence of mediation by pain, or confounding by age, strength, or alignment.
The link between aerobic exercise and function outcome is consistent with the long-term benefit of aerobic exercise on disability in activities of daily living, as demonstrated in the Fitness, Arthritis, and Seniors Trial (30), and is consistent with the cross-sectional relationship between low aerobic capacity and poor function (6). Those subjects who sustained high function were performing the greatest amount of aerobic exercise. Adjustment for each of several factors, BMI, knee pain intensity, mental health, proprioceptive inaccuracy, self-efficacy, or strength, did not attenuate the relationship between aerobic exercise and function outcome, suggesting that aerobic exercise did not act through these factors, at least as measured here. The effect of aerobic exercise may be mediated by improvement in aerobic capacity or aspects of neuromuscular function not captured by strength and the accuracy of knee-motion detection.
Specific, coordinated quadriceps and hamstring activity is required to achieve the knee and hip movements that occur during the chair-stand task. Given the muscle specificity of this task, and the abundant evidence of a cross-sectional relationship between strength and function (6, 11, 31–35), it is surprising that the protective effect of strength was not greater and that there was attenuation after adjustment. However, these results are consistent with the relatively modest effect of strengthening exercise on physical function in the long term (36), and with the finding, in both of the studies that have considered this question, that strength does not protect against knee OA disease progression (14, 37). As a muscle parameter, strength may not be the best surrogate for the vast contribution from muscle to joint function and task performance; other measures of muscle activity may be more closely related to the risk of poor physical function.
The strength–function outcome relationship was lost after additional adjustment for self-efficacy. Our results support a close relationship between strength, knee pain intensity, and self-efficacy in their effect on physical function in knee OA. Pain may acutely reduce the maximal voluntary contraction and lead to chronic activity revision or avoidance. A downward spiral of pain, weakness, and reduced self-efficacy may lead to substantial reduction in activity. In support of this paradigm, subjects with knee OA and pain were weaker than those without pain (34), and in OASIS, there was evidence of an interaction between strength and pain (38) as well as strength and self-efficacy (7), in evaluating the effects on physical function.
Proprioceptive inaccuracy, measured as a greater delay before detecting slow, passive knee motion, was associated with a poor chair-stand performance outcome (approaching significance). Various approaches to assess joint-position sense have been developed and applied in clinical studies, which reflect the status of different pathways that contribute to proprioceptive awareness under a variety of circumstances. A relationship between proprioceptive inaccuracy assessed at study baseline and physical function over the ensuing years has not previously been reported. Proprioceptive accuracy declines with age (13), was worse in persons with OA even in their nonarthritic knee than in healthy elderly subjects (10), and was correlated with physical function in cross-sectional studies of knee OA (13, 39–41). The results of the current study are noteworthy, especially since this was a passive test; dynamic joint-position sense inaccuracy may play a greater role in physical tasks and activities and more strongly predict physical function outcome.
Knee alignment strongly influences the risk of tibiofemoral OA disease progression (12). In the current study, malalignment as a continuous variable was not significantly linked to function outcome. However, as we have previously reported, the malalignment–function relationship in knee OA appears to be nonlinear; participants with 2 knees that had alignment of ≥5° (either varus or valgus) were more likely to experience a poor function outcome than were those with both knees more neutrally aligned (12).
Both baseline knee pain intensity and the baseline to 18-month change in pain predicted function outcome. There is a paucity of information concerning the longitudinal relationship between pain intensity and physical function in knee OA. In the OASIS study, baseline knee pain intensity during ambulation and transfer predicted a decline in performance during stair-climb and car tasks, respectively, but not self-reported function (38). The relationship between knee pain intensity and function decline was not significant after accounting for self-efficacy and the self-efficacy–strength interaction (7). In the National Health and Nutrition Examination Survey I, presence of knee pain predicted difficulty in mobility, transfer, and instrumental activities of daily living 10 years later (42). Other reports describe a cross-sectional relationship between knee pain and function in those with knee OA (6, 43) and in studies not limited to persons with OA (35, 44).
Age predicted the chair-stand performance outcome, which is consistent with the finding that age was associated with an increased risk of losing mobility over the next 4 years in the Established Populations for Epidemiologic Studies of the Elderly (45). The current study is notable in 2 ways. First, a longitudinal relationship between age and function outcome, adjusting for comorbidity, was demonstrated in a cohort of individuals with established knee OA. Second, the examination of neuromuscular factors afforded an opportunity to explore mechanisms of the age effect. Although greater age is associated with reductions in strength and proprioceptive acuity, the age–function relationship did not appear to be mediated by these factors. It remains possible that age exerts its effect via other neuromuscular factors, i.e., sensory and/or motor impairments not captured by strength or the accuracy of detection of passive motion.
We found a relationship between BMI at baseline and the WOMAC function outcome over 3 years. A longitudinal relationship between BMI and physical function in individuals with knee OA has not been previously reported. In cross-sectional studies not limited to individuals with OA, obesity was associated with self-reported difficulty with activities (by Health Assessment Questionnaire, in the lower limb) even after adjusting for pain (43), and higher body weight was associated with slower task performance (35).
A relationship between depressive symptoms and physical function has been described in longitudinal studies not limited to individuals with arthritis, as summarized by Ormel et al (46), and in cross-sectional studies of knee OA (31, 34, 47, 48). The demonstration in the current study that the status of mental health predicts subsequent physical function is important, given how function assessment might be biased by depressive symptoms.
The approach of the current study provided an opportunity to describe persons with knee OA in specific outcome subgroups. The values presented in Tables 5 and 6 are unadjusted, but in this format, they illustrate the attributes of individuals who sustain high function or low function as they might be encountered in clinical or screening settings. Those who sustained high function had the best values for most factors, but their high self-efficacy, low BMI, low pain intensity, and greater level of aerobic exercise were especially noteworthy.
The distinctive characteristics of the function subgroups would not have been evident if “change” in a function measure had been the defined outcome. The choice, in some observational studies, to focus on change may be intended as a way of inferring causation. However, in OA, change may require several years. The number of individuals who showed no change in function over 3 years was substantial: 98 (42%) remained in the same WOMAC group, and 105 subjects (44%) remained in the same chair-stand group. A focus on change ignores those with persistently high or low function, and thus effectively lumps these individuals together in the same group and reduces the ability to detect the effects of factors responsible for an individual's state of function. In a chronic disease that is slow to evolve, factors related to persistent low- or high-function states are of particular importance to the development of prevention or intervention programs.
This study has limitations. It would have been of value to separately analyze the effect of a risk factor on change in function status and on persistence in a given group. However, the modeling to achieve this required problematic post hoc exclusions of groups of subjects. Our approach gave weight to the need to identify factors linked to the persistence of low-function states or decline, both of which are problematic to the individual. We were able to confirm the findings separately in women, but not in men, due to the smaller number of men in the cohort. This confirmation in women was important, given that the impact of knee OA on physical function has been shown to be greater in older women than in other age and sex subgroups (42). The small amount of change in most factors between baseline and 18 months limited our ability to evaluate the impact of change in a given factor with outcome. Also, it is possible that a larger sample may have enabled us to detect an effect of the 18-month data. The absence of a link between comorbidity and function outcome may be related to the small number of comorbidities present, on average, in this cohort.
These results have implications for future studies and for strategies to optimize physical function in knee OA. Treatment of pain is believed to be the crux of disability prevention in knee OA, and the results of the current study provide additional, longitudinal support for this. However, several modifiable factors were identified that were independently linked to function outcome after adjusting for pain intensity, which supports a multifaceted approach. Results of short-term studies have suggested the greater benefit of combined approaches (e.g., acupuncture/diet/exercise versus pain therapy alone ). Moreover, the effect sizes for strengthening interventions appear to be enlarged by incorporating pain management, attention to psychosocial factors, self-management, or aerobic exercise into the intervention (50, 51).
The current study supports a key place for self-efficacy enhancement in strategies to optimize physical function. Components of perceived self-efficacy include skill, experience, general self-worth, and motivation (20); each of these is addressed in self-management education, which has been shown to be beneficial in short-term studies in arthritis patients (52). Our results suggest that aerobic exercise may have greater impact than a general increase in physical activity. Although orthoses specifically for varus-valgus laxity may have value and should be developed, novel dynamic approaches are also emerging. Fitzgerald et al tailored agility and perturbation training techniques, which were used for anterior cruciate ligament deficiency, to address the functional instability of individuals with knee OA (27). Such techniques may also enhance periarticular muscle activity and dynamic proprioceptive acuity. The effect of exercise that is restricted to strengthening has been modest in long-term trials (36). Although strength maintenance is important, parameters of periarticular muscle function other than strength may better predict a good physical function outcome and may constitute a better target for disability-prevention strategies.
In conclusion, factors placing individuals with knee OA at greater risk of a poor function outcome by at least 1 of the 2 function measures included the local factors laxity and proprioceptive inaccuracy, as well as age, BMI, and knee pain intensity. Factors protecting against a poor function outcome included strength, the psychosocial factors mental health, self-efficacy, and social support, and the activity factor amount of aerobic exercise per week. The identification of these factors describes individuals with knee OA who are at greater risk of a poor physical function outcome and provides possible targets for rehabilitative and self-management strategies to prevent disability.