Awareness is increasing that nonpharmacologic measures are the keystone of management of patients with symptomatic knee osteoarthritis (1, 2). Analgesics and nonsteroidal anti-inflammatory drugs augment the benefits of measures such as patient education about principles of joint protection; weight loss (if the patient is obese); and an exercise regimen that improves or maintains range of motion of the involved joint, strengthens periarticular muscles, and improves cardiovascular fitness. However, although a number of studies have described symptomatic benefit in patients with knee osteoarthritis following a variety of types of exercise (3-5), data on whether periarticular muscle strengthening affects the progression of structural damage have been unavailable. In the study by Sharma and colleagues in this issue (6), greater quadriceps strength at baseline was associated with an increased likelihood of radiographic progression of knee osteoarthritis among patients with varusvalgus laxity of the knee, demonstrated by mechanical testing or varusvalgus malalignment of the knee on full lower-limb radiographs. Radiographic progression was defined as a decrease in the interbone distance in the medial tibiofemoral compartment in paired knee radiographs obtained at an 18-month interval, using a protocol shown to afford reproducible positioning of the joint (7). A decrease in joint space width is generally considered to indicate thinning of articular cartilage. Sharma and colleagues concluded that greater quadriceps strength did not compensate for the adverse effects of malalignment or varusvalgus laxity on progression of cartilage loss in the osteoarthritic knee. They suggested that physical therapy regimens aimed at strengthening the quadriceps muscle may in fact increase structural damage of the joint in some patients with knee osteoarthritis. They also suggested that individualized physical therapy approaches designed to take into account the perspective of the local mechanical milieu of the osteoarthritic knee may be required. The importance of periarticular muscle weakness in patients with knee osteoarthritis has been recently emphasized by studies suggesting that quadriceps weakness may not only be a result of symptomatic knee osteoarthritis (often due to disuse atrophy arising from avoidance of load-bearing on the painful extremity or to reflex inhibition of quadriceps contraction) ( 8, 9) but may also be present in some persons with no history of joint pain or evidence of muscle atrophy. In addition, quadriceps weakness may antedate radiographic evidence of osteoarthritis. Thus, it may be a risk factor for, as well as the consequence of, knee osteoarthritis (10). On the basis of these observations, a placebo-controlled study was recently performed to determine whether a muscle-strengthening regimen can prevent the development or reduce the severity of knee pain and radiographic changes of osteoarthritis in elderly persons. The results are currently being analyzed (Mikesky A, Brandt K, Mazzuca S. Effect of a muscle strengthening program on prevention of knee pain and radiographic changes of osteoarthritis in elderly subjects. In preparation). Sharma and colleagues concluded that a need exists to develop subset-specific approaches to enhance joint-protective muscle activity. This may indeed be the case. If so, it would substantially change our approach to physical therapy for patients with knee osteoarthritis. However, some caveats should be raised regarding Sharma and colleagues' interpretation of their results. For example, isokinetic dynamometry, which was used to assess quadriceps strength, was performed only at baseline. Because no subsequent measurements of quadriceps strength were obtained, it is not clear that greater quadriceps strength caused radiographic progression of osteoarthritis. Alternatively, patients with the greatest quadriceps strength at baseline may have lost strength during follow-up, perhaps as a result of reduced loading of the arthritic extremity, and unrecognized loss of strength, rather than the magnitude of quadriceps strength at baseline, may have contributed to the progression of structural damage in the osteoarthritic knee. Because the study was not designed to assess symptoms of knee osteoarthritis, no information is available about the relationship between the observed loss of radiographic joint space and knee pain or function. It is not clear how patients with greater quadriceps strength at baseline fared over the course of the study with respect to knee pain and function. Are patients with knee osteoarthritis who have a strong quadriceps protected from knee pain or decreased function? Is loss of quadriceps strength in patients with knee osteoarthritis associated with an increase in joint pain or functional impairment? If so, is this preventable? It is unclear how the presence of knee pain at the time of testing affected the results of isokinetic dynamometry. Did the patients who exhibited greater quadriceps strength have the least amount of knee pain during testing? Did they use fewer analgesics, psychotropic drugs, and muscle relaxantsall of which might have affected the results of strength testingthan patients with decreased quadriceps strength? Sharma and colleagues' interesting results are hypothesis generating rather than conclusive evidence that standard quadriceps-strengthening exercise programs are detrimental to patients with osteoarthritis who exhibit greater quadriceps strength than others. If the authors' interpretation of their data is correct, their findings have significant implications for the treatment of patients with knee osteoarthritis. However, more data are needed before we conclude that quadriceps-strengthening exercise harms some patients with knee osteoarthritis and subsequently modify our approach to physical therapy to recommend that strength-maintenance programs be tailored specifically to particular subsets. A large-scale study of the natural history of knee osteoarthritis (the Osteoarthritis Initiative [OAI]), which will soon be initiated with funding from the National Institutes of Health and the pharmaceutical industry, will provide large cohorts of patients at high risk for incident osteoarthritis and progression of established knee osteoarthritis. This study will give researchers opportunities to longitudinally evaluate changes in lower-extremity muscle strength within these cohorts. The relationship of such changes to pain and function and to the development and progression of structural joint damage, assessed radiographically and by magnetic resonance imaging, will also be assessed in people with knee osteoarthritis, with and without varusvalgus malalignment and laxity. Over the past few years, Dr. Sharma's important work in patients with knee osteoarthritis has emphasized the significance of local mechanical abnormalities in the pathogenesis of joint damage (11, 12). It is reasonable to consider that quadriceps weakness (or perhaps, as she and her colleagues suggest, quadriceps strength) may be a surrogate marker for the progression of osteoarthritis in some patients. The OAI is well suited to the examination of that possibility. The search for biomarkers of osteoarthritis progression should not be limited to changes in the concentration in plasma or urine of molecules derived from articular cartilage or subchondral bone in the osteoarthritic joint. Finally, in future clinical trials of pharmacologic agents that may prevent or slow the progression of structural damage in osteoarthritic joints (that is, disease-modifying osteoarthritis drugs), it should be recognized that the local mechanical environment of the joint may influence efficacy. In interpretation of the effects of disease-modifying osteoarthritis drug therapy on changes in radiographs or magnetic resonance imaging, it is important to consider that quadriceps strength; malalignment; instability; and neurologic deficits, such as an impairment in proprioception, may modify the pharmacologic effect.
Annals of Internal Medicine