The aim of treatment of patients with osteoarthritis (OA) is to improve pain and function and, ideally, to prevent progression of structural damage. Therapeutic agents that prevent the development, or slow the progression, of structural changes of OA have been designated disease-modifying OA drugs (DMOADs). Definitions of DMOAD activity have been proposed (1–3), and guidelines for radiographic evaluation of structural damage in OA have been developed (1–4). DMOADs may be directed at any of the structural changes in OA, such as destruction of articular cartilage, osteophytosis or osteosclerosis, cyst formation, or attrition of bone, although it is generally considered that the most promising target for DMOAD development is prevention of cartilage destruction. The clinical benefits of effective “chondroprotective” therapy, however, remain unknown.
A variety of methods for imaging the joint have been proposed (e.g., ultrasound, magnetic resonance imaging), but it is generally considered that measurement of joint space width (JSW) is currently the best available surrogate for evaluation of the progression of cartilage destruction. Measurement of JSW is recommended by both the US Food and Drug Administration and the European Agency for the Evaluation of Medicinal Products Human Medicines Committee as a primary end point in clinical trials of DMOADs (5, 6). JSW can be assessed by measurement of the interbone distance at its narrowest point (minimum JSW), as the mean width, or as joint space surface area (JSA), using a graduated eyepiece and/or image analysis systems (7–10).
In patients with hip OA, the progression of joint space narrowing (JSN) has been evaluated in several studies, with good agreement that the annual rate of JSN is ∼0.15 mm (1, 11). For evaluation of radiographic progression of hip OA, minimum JSW has been demonstrated to be more sensitive to change compared with mean JSW or measurement of surface area, and measurements have been shown to be optimized by use of an image analysis system, in comparison with use of a graduated eyepiece (12). However, measurement of minimum JSW using a 0.1-mm–graduated eyepiece was sufficiently sensitive to demonstrate a chondroprotective effect of the drug diacerein in patients with hip OA (13).
The assessment of radiographic progression of knee OA has generally been based on measurement of JSW in the femorotibial compartment in standing anteroposterior (AP) radiographs of the extended knee. Although evidence that glucosamine sulfate has DMOAD activity has been reported recently in studies using standing AP radiographs (14, 15), the rate of the progression of JSN in patients with femorotibial OA has been extremely variable in published reports (16), due, in large part, to differences in the reliability of the various radiographic methods that have been used.
Measurement of femorotibial compartment JSW is influenced by a number of variables, including the degree of weight-bearing, alignment of the medial tibial plateau with the central x-ray beam, rotation of the knee, and the degree of knee flexion (17–19). Fluoroscopy has been recommended as a means of standardizing the position of the knee in serial radiographic examinations (4). In the fluoroscopically assisted AP view described by Buckland-Wright et al (9), the position of the x-ray beam is fixed, and the knee is flexed (usually 7–9°) to facilitate alignment of the medial tibial plateau with the central x-ray beam.
The Lyon schuss view is a posteroanterior (PA) radiograph of the knee in flexion. The degree of flexion is a result of positioning the patient with the tips of both great toes, the knees, and the pelvis coplanar and in contact with the examination table. The resulting degree of knee flexion varies from 20° to 30°, depending on the relative length of the feet and tibiae.
It has been suggested that the greater degree of knee flexion afforded by the Lyon schuss view, in comparison with the standing AP view, increases the sensitivity of the former approach to JSN (18). However, long-term evaluation of the progression of JSN in the OA knee using standardized radiography that combines fluoroscopic positioning and a significant degree of fixed flexion of the knee has not been described previously. Furthermore, a comparison of various methods of measuring the change in JSW in knee radiographs has rarely been reported (20). The present study was undertaken to evaluate the progression of JSN in OA knees imaged in both the standing AP and Lyon schuss positions, as assessed by changes in minimum JSW, mean JSW, and JSA, using an image analysis system.
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- PATIENTS AND METHODS
The 3 joint space measurements performed in the present study were highly reproducible using the new image analysis system. Reproducibility of measurement was unrelated to JSW, especially when the minimum JSW was <4 mm. A comparison of the reproducibility of this method with those previously described is difficult, however, because the kappa statistic has not been reported systematically in earlier studies. Nonetheless, acceptable coefficients of variation for manual and automated methods of joint space width measurement have been reported previously (16).
In the present study, the reproducibility of measurements of JSN was evaluated by repeated measurement of the same image. However, in evaluating the progression of JSN, measurement of JSW must involve analysis of serial radiographs of the same knee. It is important to note, therefore, that the rate of JSN may vary because of differences in radioanatomic positioning between examinations. For example, the coefficient of variation for hip JSW varied from 1.1% to 3.3% in repeated measurements of the same radiograph and also in different radiographs of the same joint (10).
Adequate evaluation of the reproducibility of a radiographic method requires the analysis of multiple radiographs of the same joint, obtained in different centers on the same day. Although a protocol of this type was not authorized for the present study by the ethics committee at our institution, we previously reported an intraobserver kappa value of 0.76 for minimum JSW in Lyon schuss radiographs (18). The large difference between the kappa values obtained for repeated measurements of JSW in the same radiograph and in repeated images of the same knee (0.98 and 0.76, respectively) clearly indicates that the reproducibility of measurements in a longitudinal trial is highly dependent on the quality of the radiograph and emphasizes that measurements of serial changes in JSW in the femorotibial joint are highly dependent on changes in the radioanatomic position of the knee (16–20). It is an advantage of the Lyon schuss view, relative to the standing AP view that, because the knee is in contact with the examination table, the effects of radiographic magnification are minimal. Magnification in the standing AP view has been reported to be as great as 34% (9).
Additional advantages of the Lyon schuss radiograph are the fixed degree of flexion of the tibiofemoral angle it provides (because the patient is positioned with both knees and the pelvis in contact with the table), and the good alignment of the tibial plateau with the central x-ray beam (which is achieved by use of fluoroscopy). Another benefit, as shown in the present study, is greater sensitivity to change in JSW with the Lyon schuss technique, in comparison with the standing AP radiograph, because the Lyon schuss position, due to its degree of flexion of the knee, places the areas of the femorotibial surfaces that exhibit the greatest cartilage damage in contact. The results of the present study confirm that PA radiographs obtained with the knee in 20–30° of flexion afford greater sensitivity to change in JSN than does the standing AP radiograph. In theory, the relatively poor sensitivity of the standing AP view to progressive changes in articular cartilage thickness in knee OA may be compensated for in the design of studies of OA progression by using an appropriate increase in sample size, based on an estimate of error variation in JSN estimates. However, it has been demonstrated recently that the increase in sample size necessary to negate an error of such magnitude is prohibitively large (i.e., 10-fold to 16-fold greater than that needed with fluoroscopically standardized radiography) for studies of 2–3 years duration (23).
Indeed, in the present study, a statistically significant reduction in minimum JSW over the 2-year interval of followup was noted only in the Lyon schuss radiographs and was not detected in the standing AP views (Table 1). Furthermore, the SRMs were nearly twice as great in the Lyon schuss images as in the standing AP radiographs. JSW, both at baseline and at the 2-year examination, was significantly smaller in the Lyon schuss radiographs than in the standing AP views (P < 0.01), probably related to the greater contact of the joint surfaces at the site of maximum cartilage destruction. The degree of knee flexion in the Lyon schuss view, as judged from the depth of the intercondylar notch, is less than that in the tunnel view, but considerably greater than that in the semiflexed fluoroscopically positioned AP radiograph described by Buckland-Wright (9), in which it averages 7–9°.
Although satisfactory alignment of the tibial plateau in both members of the pair of Lyon schuss radiographs was achieved in only 66% of cases, it should be noted that the radiographs were obtained in a variety of radiology departments by a variety of radiology technicians who had not been trained formally in its performance (although they had received written instructions describing the technique). In the present study, a trained radiology technician in our department at Lyon obtained the radiographs, and nearly 90% of the pairs exhibited good alignment in both images. This point is relevant, because the sensitivity to changes in JSW in the Lyon schuss view was highly dependent on the quality of tibial plateau alignment: the highest value for SRM (i.e., 0.51) was observed in minimum JSW measurements in pairs of Lyon schuss radiographs that exhibited satisfactory alignment in both images. In contrast, in the standing AP radiographs, the SRM for JSN was unrelated to alignment. This discrepancy may have been attributable to the fact that alignment alone is insufficient to assure high sensitivity to change in JSW, and that fixation of the femorotibial angle, which is achieved in the Lyon schuss view but not in the standing AP view, is a major determinant of sensitivity to change.
It should be noted that in the present study, the percentage of poorly aligned Lyon schuss radiographs was only marginally smaller than that of poorly aligned standing AP views. This is not surprising, insofar as fluoroscopically assisted positioning of the knee was used in both protocols. Because fluoroscopy was used to optimize the quality of tibial plateau alignment in the standing AP radiographs, the difference between results obtained with the 2 imaging protocols could result only from the greater degree of knee flexion required in the Lyon schuss view and the minimal impact of radiographic magnification associated with that technique. For this reason, the proportion of standing AP radiographs that exhibited adequate alignment in both members of the pair was much higher in this study than in a study of conventional standing AP radiographs obtained without use of fluoroscopy (19). A nonfluoroscopic protocol for radiography of the knee in fixed flexion, in which positioning of the joint is essentially identical to that in the Lyon schuss view, was recently described by Peterfy et al (24), but results of longitudinal studies in patients imaged with that protocol have not been published.
In the present study, serial pairs of well-aligned standing AP radiographs were notably less sensitive to JSN than were those identified by Mazzuca et al (19) in their analysis of alignment in standing AP radiographs from extant research cohorts (SRM = 0.19 and 0.96, respectively). This discrepancy may be explained by the fact that Mazzuca et al identified paired radiographs in which fortuitous alignment of the tibial plateau occurred relative to a fixed horizontal x-ray beam; because of the fixation of the beam, the investigators did not have an opportunity to compensate for changes in the amount of joint loading and/or degree of knee extension in the 2 examinations, although an adjustment of the beam angle, as was possible in the present study, might have negated the effects of such changes. In contrast, fluoroscopically assisted adjustment of the angle of the x-ray beam in the present study resulted in a greater proportion of knees exhibiting good tibial plateau alignment in both radiographs compared with the proportion in the study by Mazzuca et al (57% and 14%, respectively). In many cases, however, negation of a change in alignment may not have compensated for a change in the degree of joint extension (as reflected in the femorotibial angle), which results in unpredictable changes in JSW.
It is clear that highly reproducible radioanatomic positioning is essential for accurate evaluation of the progression of femorotibial JSN in patients with knee OA (19). Although the parameters used to evaluate JSN in the present study (i.e., changes in minimum JSW, mean JSW, and JSA) displayed similarly high levels of reproducibility in repeated measurements of the same image, in both the Lyon schuss and standing AP radiographs the SRM for minimum JSW was greater than that for mean JSW or JSA (Table 1). However, the SRM of minimum JSW was very much dependent on alignment of the tibial plateau, while the SRMs of mean JSW and JSA were apparently less influenced by this. Measurement of minimum JSW has been widely used in previous studies of JSN (7, 9, 10, 13–15, 19). Based on the results of the present study, when highly standardized radioanatomic positioning of the knee is achieved in serial examinations, minimum JSW is the preferred parameter for determination of OA progression in serial radiographs.