Knee osteoarthritis (OA) is one of the leading causes of chronic disability among older individuals (1). An accurate indicator of disease progression is critical for studies of this condition. Thinning, erosion, and loss of hyaline articular cartilage are considered the hallmark of OA. In clinical studies on the natural history of knee OA and in clinical trials assessing treatment efficacy for knee OA, worsening of joint space narrowing seen on knee radiography, which is thought to reflect articular cartilage loss, has served as one indicator of structural disease progression. Although serial radiography is a noninvasive and inexpensive means to evaluate progression of joint space narrowing, it remains an indirect measure of cartilage loss.
There are several potential disadvantages of using knee radiographs as an assessment of cartilage loss over time. First, progression of joint space narrowing is determined as the distance between the femur and tibia at only 1 point of contact during standing, and therefore cartilage loss occurring along other areas of the femur and tibia in contact during the flexion/extension excursion of the knee would not be captured. In addition, the distance between the femur and tibia represents more than just hyaline articular cartilage, since the meniscus is lying in the same space. Therefore, in some instances progression of joint space narrowing could reflect meniscal extrusion rather than true cartilage loss (2). Since strategies that optimize reproducibility and accuracy of knee radiographic joint space measurement focus on the medial compartment (3), the ability of radiography to evaluate changes in the lateral compartment of the knee may be more limited. Last, radiographic progression is unlikely to be sensitive to small changes in cartilage.
Magnetic resonance imaging (MRI) offers a distinct advantage over knee radiography, since cartilage can be assessed directly. Several studies have been performed evaluating MRI as an imaging tool for knee OA (4–8). Since MRI also provides 3-dimensional imaging of the knee, in contrast to the 2-dimensional radiographic images, cartilage morphology in multiple compartments of the knee can be better assessed.
Radiographic joint space narrowing has been accepted as a proxy measure of articular cartilage thickness based on evidence showing a correlation between cross-sectional assessments of radiographic joint space narrowing and several different measures of cartilage morphology, including arthrography (9, 10). However, few longitudinal studies have evaluated the changes in cartilage in the knee in relation to radiographic progression (11). No study, to our knowledge, has examined the longitudinal association between radiographic progression of joint space narrowing and the location of MRI-based cartilage loss. Furthermore, it is unknown how often substantial cartilage loss occurs and remains undetermined by radiographic assessment. In this study, we examined progression of joint space narrowing on knee radiographs, and its association with changes in articular cartilage at the tibiofemoral joint as measured using MRI in a large sample of older men and women followed up for 30 months.
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- PATIENTS AND METHODS
In this longitudinal study of >200 older men and women with symptomatic knee OA whose disease progression was followed up for up to 30 months, cartilage loss on MRI was more frequently detected than was progressive radiographic joint space narrowing. Although we found radiographic progression to be strongly predictive of cartilage loss in both the medial and lateral compartments, radiographic findings were not a sensitive indicator of cartilage loss, with a substantial proportion of knees with cartilage loss detectable by MRI having no discernable radiographic progression of joint space narrowing. While sensitivity was low, the specificity of radiography for the evaluation of cartilage loss was high, suggesting that if radiographic progression is noted, cartilage loss is likely to be seen.
As would be expected, loss of cartilage tended to occur most frequently in the load-bearing sites of the central femur and tibia, particularly in the medial compartment. Loss of cartilage in these sites was more likely to be detected on radiographs as well. We also found that cartilage loss frequently occurred in the posterior femur, a site that articulates with the tibia during flexion of the knee, and thus is a key potential site for disease occurrence. The presence of cartilage loss along the posterior femur would not be adequately assessed on radiographs, and indeed, we found that among those who had evidence of cartilage loss on MRI without visible radiographic progression, loss of cartilage tended to occur more frequently in the posterior femur region. Overall, the anterior and posterior regions of the tibia were not frequent sites for cartilage loss in either the medial or lateral compartment; this may reflect protection from loss conferred by coverage of the meniscus.
Given the high specificity of radiographic results, we found only a small proportion of individuals who had progression of radiographic joint space narrowing during followup but no detectable changes in cartilage by MRI. When we examined the baseline cartilage scores for these “false-positive” radiographic progressor knees, they tended to be worse than in those who had neither MRI nor radiographic changes (data not shown). The radiographic progression of joint space narrowing in these individuals may have represented meniscal extrusion (2). Further study on the contribution of both meniscal disease and cartilage loss to changes in radiographic joint space width is needed, and will be the topic of another report.
Few studies of knee OA to date have used MRI to assess cartilage loss longitudinally. One study failed to identify substantial cartilage loss, or even radiographic progression, in 11 subjects with knee OA followed up for 3 years (17). Unlike our study, that study used a quantitative measure to assess cartilage loss. However, 2 other studies also using quantitative measures of cartilage identified substantial cartilage loss in subjects with knee OA (11, 18). The largest study, with >100 patients followed up for almost 2 years, did not examine the relationship of cartilage loss to radiographic changes (18). The other study, which demonstrated cartilage loss in >30 subjects followed up for 24 months, showed no apparent relationship to radiographic changes (11); however, the number of subjects was small.
In 2 studies in which semiquantitative scales were used to assess knee cartilage morphology, cartilage loss was demonstrated during followup (7, 19). In 1 study of 20 subjects with knee OA who were followed up for 1 year, significant radiographic changes were not identified despite changes in cartilage morphology (7). No information was provided on the location of cartilage loss detected. The other study involved >40 subjects who underwent repeated MRI after an average of 2 years (19). Although not all subjects had a diagnosis of knee OA, the percentages with cartilage loss in the medial and lateral compartment were comparable with our findings. Similar to our study, those investigators demonstrated that cartilage loss tends to occur primarily at central weight-bearing sites (19). No comparison of cartilage loss with radiographic changes was reported.
While we studied a modest number of subjects and followup was limited to 30 months, we still identified a substantial proportion of individuals with progressive cartilage loss seen on MRI. Our study sample included a greater proportion of men, which reflects the VA population from which subjects were recruited. Although we did not use continuous measures to assess progression of joint space narrowing in this study, we did use a highly reliable, well-validated scale (15). Furthermore, the proportion of subjects with medial and lateral radiographic progression in our study was comparable with findings in other large, community-based, longitudinal studies of subjects with knee OA in which a similar semiquantitative scale was used to assess radiographic joint space narrowing (20). We also used a semiquantitative method to score cartilage change. We believe this serves as a better method for determining location of cartilage loss within the knee than cartilage volume and is more likely to detect focal deficits in cartilage, which was relevant in our comparison between radiographic and MRI results. Finally, we evaluated cartilage loss using a scale that may not be sensitive to modest degrees of focal loss. If we had used a more sensitive scale for cartilage loss, the sensitivity of radiography as a tool would likely have been even lower.
In summary, we found that readily detectable tibiofemoral hyaline articular cartilage loss occurs frequently during 30-month followup in older men and women with symptomatic knee OA, and we provide longitudinal evidence that radiographic joint space progression is predictive of the cartilage loss detected on MRI. Our data also suggest that if progressive joint space narrowing is seen on radiographs, it more often reflects cartilage loss in the central region of the weight-bearing surface than other areas. However, while we found that radiographic progression of joint space narrowing had high specificity for cartilage loss, it was not a sensitive measure, with cartilage loss still occurring frequently, particularly in the posterior femur, when no progression was apparent on radiography. If radiography is used alone in longitudinal studies of knee OA, a substantial proportion of knees with progression of cartilage loss will be missed.