Why radiography should no longer be considered a surrogate outcome measure for longitudinal assessment of cartilage in knee osteoarthritis

Abstract

Imaging of cartilage has traditionally been achieved indirectly with conventional radiography. Loss of joint space width, or 'joint space narrowing', is considered a surrogate marker for cartilage thinning. However, radiography is severely limited by its inability to visualize cartilage, the difficulty of ascertaining the optimum and reproducible positioning of the joint in serial assessments, and the difficulty of grading joint space narrowing visually. With the availability of advanced magnetic resonance imaging (MRI) scanners, new pulse sequences, and imaging techniques, direct visualization of cartilage has become possible. MRI enables visualization not only of cartilage but also of other important features of osteoarthritis simultaneously. 'Pre-radiographic' cartilage changes depicted by MRI can be measured reliably by a semiquantitative or quantitative approach. MRI enables accurate measurement of longitudinal changes in quantitative cartilage morphology in knee osteoarthritis. Moreover, compositional MRI allows imaging of 'pre-morphologic' changes (that is, visualization of subtle intrasubstance matrix changes before any obvious morphologic alterations occur). Detection of joint space narrowing on radiography seems outdated now that it is possible to directly visualize morphologic and pre-morphologic changes of cartilage by using conventional as well as complex MRI techniques.

Figure 1

Radiographs at baseline and 2-year follow-up of a 61-year-old woman with osteoarthritis. At two time points, radiographs were taken with 5°, 10°, and 15° angulation of the knee. (a) Anteroposterior (AP) radiograph taken at 5° angulation shows medial joint space narrowing (OARSI grade 2 and Kellgren-Lawrence grade 3). (b) However, AP radiograph taken at 10° angulation shows OARSI grade 3 joint space narrowing (Kellgren-Lawrence grade 4). (c) Similarly, at follow-up, AP radiograph taken at 5° angulation shows OARSI grade 2 joint space narrowing (Kellgren-Lawrence grade 3) whereas that taken at 15° angulation (d) shows OARSI grade 3 joint space narrowing (Kellgren-Lawrence grade 4). If images (b) and (c) are compared longitudinally, one observes a paradoxical 'joint space widening'. This example highlights the importance of technique to ascertain the reproducibility of the same angulation of the knee in longitudinal studies. OARSI, Osteoarthritis Research Society International.

Figure 2

Comparison of an anteroposterior radiograph and a coronal magnetic resonance image of the knee. (a) Anteroposterior radiograph of the left knee demonstrates marginal osteophytes of the medial and lateral femur and tibia (arrows). Joint space width appears normal in the lateral tibiofemoral compartment, but there is mild to moderate medial tibiofemoral joint space narrowing. No other obvious bony abnormalities are seen. (b) Coronal fat-suppressed proton density-weighted magnetic resonance imaging performed on the same day reveals a subchondral bone marrow lesion (thin white arrow) at the medial tibial plateau subjacent to a focal full-thickness cartilage defect. Multiple partial-thickness defects of the medial femoral condyle cartilage (white arrowheads) are also noted. Notably, focal full-thickness cartilage defects (gray arrowhead) are more extensive at the lateral femoral condyle and subchondral bone (black arrowheads) is almost completely denuded at the lateral tibial condyle, despite radiographically normal appearance of the lateral tibiofemoral joint space width. Most of the joint space narrowing of the medial tibiofemoral joint is secondary to a partially macerated and extruded medial meniscus (thick white arrow). Additionally, there is attrition of the medial and lateral tibial plateaus and marginal osteophytosis. This example demonstrates why radiography should no longer be considered a surrogate outcome measure for longitudinal assessment of cartilage in knee osteoarthritis.

Figure 3

Example of non-sensitivity of radiography. (a) Baseline coronal intermediate-weighted magnetic resonance imaging shows hyperintensity in the weight-bearing portion of the lateral tibial plateau but no definite cartilage defect. (b) At 24-month follow-up, an incident focal full-thickness defect has developed in the corresponding area of the lateral tibial plateau (arrows). (c) Baseline anteroposterior radiograph does not show any joint space narrowing in the lateral tibiofemoral joint. (d) No change to baseline is observed at 24-month follow-up.

Figure 4

Example of non-sensitivity of radiography. (a) Baseline sagittal intermediate-weighted fat-suppressed image shows normal articular cartilage coverage in the medial femur and tibia. (b) At 24-month follow-up, there is circumscribed thinning of cartilage in the posterior medial femur (arrows). (c) Baseline radiograph does not show any abnormalities in regard to joint space width or any definite osteophytes at the medial tibia (no arrow). (d) At 24-month follow-up, no change is observed in comparison with the baseline image.

Figure 5

Example of non-specificity of radiography. (a) Baseline sagittal intermediate-weighted fat-suppressed image shows discrete superficial cartilage loss at the central part of the medial femur (arrows). (b) No progression is seen at 24-month follow-up (arrowheads). (c) Radiographic joint space narrowing is depicted at baseline (arrowheads). (d) Further decrease in joint space width is shown at 24-month follow-up (arrows) and was due to meniscal extrusion (not shown).

Figure 6

dGEMRIC images of knees in an individual without evidence of radiographic osteoarthritis (Kellgren-Lawrence grade 0). (a) Before, (b) 3 months after, and (c) 1 year after meniscal repair surgery. The color scale shows values increasing from lower values (red-yellow range) to mid-high values (yellow-green range) over this time period. These images demonstrate the potential to show variations in cartilage molecular status even in regions of morphologically intact tissue and, as in this case, potentially monitor cartilage repair when relieved of trauma or with an intervention designed to improve the biomechanical status of the joint. dGEMRIC, delayed gadolinium-enhanced magnetic resonance imaging of cartilage.