Assessment of change in knee cartilage over time is a critical element of clinical trials of disease-modifying agents (1–4) and of natural history studies of knee osteoarthritis (OA) (5–8). In general, anteroposterior (AP) or posteroanterior (PA) view radiographs have been used to assess the tibiofemoral (TF) joint space width (JSW) as a correlate of cartilage thickness, and studies have evaluated the loss of JSW as a proxy for cartilage loss. Both fluoroscopically positioned and nonfluoroscopic AP or PA views with the knee in flexion achieve excellent reliability in measurements of the medial joint space. With fluoroscopically positioned radiographs, investigators can detect joint space change in the medial compartment in the time frame of a clinical trial (9–11).
For fluoroscopic positioning to be advantageous, the beam must be directed precisely parallel to the upper border of a curved tibia in the medial compartment. This requires special training of radiographic technologists and considerable quality control (12), and it entails additional cost and use of higher radiation doses than conventional radiographs. An additional limitation of this method is that only the medial compartment joint space is the focus of imaging, and this may remove from consideration the 10–20% of patients with primary lateral involvement with knee OA (13). The low sensitivity to change of nonfluoroscopic methods, together with the difficulty in implementing fluoroscopic positioning methods, has led to a scarcity of practical radiography options for clinical trials and other longitudinal studies of knee OA.
To provide another option for longitudinal assessment of the joint space, we propose the use of lateral view radiographs to image the TF joint space. The positioning of the knee for this view is simple and easy to standardize, can be done without fluoroscopic positioning, and the joint space can be visualized in both TF compartments. Figure 1 shows an example of a lateral view radiograph with the JSW in the medial and lateral compartments identified. While the lateral view of the knee could be used to evaluate the TF joint space over time, there has been no evaluation of its short-term reliability or its validity for the detection of long-term joint space loss.
Figure 1. Lateral radiograph of a knee, magnified to show the tibiofemoral joint. Top line shows the lateral joint space; bottom line shows the medial joint space.
Download figure to PowerPoint
We used data from a 30-month natural history study of symptomatic knee OA to evaluate lateral views for test–retest reliability and validity in association with mechanical axis, a strong predictor of long-term joint space loss (14). In addition, we compared the sensitivity of the lateral view with that of a fluoroscopically positioned PA view in the detection of joint space loss over time.
- Top of page
- SUBJECTS AND METHODS
Lateral view radiographs have good reliability, better sensitivity to change than fluoroscopically positioned PA views, and are valid for the assessment of TF joint space change. Lateral radiographs provide a reasonable alternative to fluoroscopically positioned AP or PA radiographs in longitudinal studies of knee OA.
We are not aware of prior attempts to evaluate the reliability and validity of the lateral view radiograph as a method to evaluate the TF joint space. The test–retest reliability of the lateral view (RMS error) is similar to that of optimally acquired fluoroscopic AP views. Measuring the reliability of fluoroscopically positioned AP radiographs at one clinical site, Mazzuca et al (21) noted an SEM (the same measure as our RMS error) of 0.32 for those of intermediate quality (versus 0.40 for poor quality and 0.25 for high quality). From different sites, the SEM was uniformly worse than we reported for the lateral view (range 0.42–0.56). Thus, the reproducibility of joint space measurement for the TF compartments visualized from the side (the lateral view) without fluoroscopic positioning is roughly equivalent to that reported elsewhere for the fluoroscopically positioned AP view (21). We should note that, while the PA and AP fluoroscopically positioned views are accepted as methods by which to follow JSN, there is, in fact, an absence of longitudinal validation for joint space loss in the PA/AP view in other studies. However, since the AP and PA views have both been used in studies documenting the potent effect of malalignment on joint space loss (6, 14), it would be reasonable to state that AP and PA views have been validated as methods to track joint space loss.
Whereas magnetic resonance imaging (MRI) techniques offer a means of directly evaluating the volume of cartilage in a knee, the Food and Drug Administration continues to require, and trialists continue to use, radiographic progression as the primary method of assessing joint space loss. Recent recommendations for the conduct of clinical trials of disease-modifying treatments in OA still regard radiographs as the primary method of assessment (22). Since the current gold standard for trials is the fluoroscopically positioned radiograph, that was the appropriate comparator. To compare lateral and PA/AP views on their correlation with cartilage loss on MRI would require an exploration into locations of cartilage loss, since the lateral view is taken with the knee in more flexion than most AP or PA views. This complicated issue will be the topic of a subsequent study.
We used goniometry to evaluate the consistency of knee flexion and prespecified an angle to use for followup of subjects, but this could be more easily accomplished with a fixed frame or other method to ensure a certain flexion angle of the knee.
We used methods of validation that have not been previously tested for radiographs, yet we recognize that they could be questioned. Testing whether malalignment increases the likelihood of progression on the lateral view is a form of construct validity. If the lateral view were a valid method for evaluating progression, malalignment should increase the risk of progression as detected on the lateral view. While we do not know exactly what progression on only the lateral view signifies, its association with malalignment suggests that it correlates with cartilage loss, just like joint space loss on the PA view. Analyses did not adjust for correlated knees, which is challenging using Wilcoxon's test. We performed additional parametric analyses using the degree of malalignment as an outcome and progression on the lateral view as a predictor and used generalized estimating equations to adjust for interknee correlation. In this analysis, differences in alignment between groups remained statistically significant (P < 0.0001 for medial progression, P = 0.0038 for lateral progression).
Lateral radiographs were read unblinded to sequence. However, we read a subset of 21 subjects' radiographs (both knees at each of 3 visits) blinded to sequence, and the reliability of the blinded readings was high and showed no tendency toward an increase in our tendency to label a knee as having progressed. While studying vertebral fractures using serial spine radiographs, Ross et al (23) found that compared with reading blinded to sequence, reading unblinded to sequence better detected known risk factors for fracture and led to fewer errors in characterizing fractures. We contend that reading all films unblinded to sequence is a more accurate way of assessing progression and is valid, especially if the reader does not know the risk factor status of the subject.
We used a semiquantitative approach to evaluate joint space loss, and a pure quantitative approach in which JSW was measured using calipers may provide more sensitivity to change than our approach. A method would need to be developed to accommodate both medial and lateral joint space loss.
There are potential drawbacks to using the lateral view. First, more knees will need to be excluded at baseline because they show bone-on-bone narrowing. Not only are the lateral views more sensitive to change than the AP or PA views but, perhaps because they visualize knees at 30–50° of flexion, knees are often markedly narrowed on the lateral view but still show considerable remaining joint space in the same compartment on the PA/AP view. We excluded from followup 99 knees that, at baseline, had bone-on-bone changes on the lateral view and would have excluded a smaller number (68 knees) if we had relied solely on the PA view. Thus, if the lateral view were used to evaluate the progression of narrowing, the number of eligible knees would be a bit lower. Second, medial and lateral compartments are sometimes hard to differentiate on the lateral view. We believe that this presumed drawback is due to lack of familiarity with the shapes and sizes of the medial and lateral femoral condyles and tibial plateaus on the lateral view. We currently find an unreadable lateral view a rarity.
In conclusion, the lateral view of the knee in a weight-bearing position can be used with validity and reliability to evaluate the joint spaces of the medial and lateral TF compartments.