Patients were recruited to participate in a natural history study of symptomatic knee OA, the Boston Osteoarthritis of the Knee Study. The recruitment for this study has been described in detail elsewhere (12). Briefly, patients were recruited from 2 prospective studies on quality of life among veterans (1 involving a male cohort and the other, a female cohort). Patients were also recruited from clinics at Boston Medical Center in Massachusetts, and from advertisements in local newspapers. Potential participants were asked 2 questions: “Do you have pain, aching, or stiffness in one or both knees on most days?”, and “Has a doctor ever told you that you have knee arthritis?”. For patients who answered yes to both questions, we conducted a followup interview in which we asked about other types of arthritis that could cause knee symptoms. If no other forms of arthritis were identified, then the individual was eligible for recruitment.
For each patient, a series of knee radiographs (posteroanterior, lateral, and skyline) was obtained to determine whether radiographic OA was present. If patients had a definite osteophyte on any view in the symptomatic knee, they were eligible for the study. Because they had frequent knee symptoms and radiographic OA, all patients met the American College of Rheumatology criteria for symptomatic knee OA (13).
The study included a baseline examination and followup examinations at 15 and 30 months. At baseline, patients who did not have contraindications to MRI underwent MRI of the more symptomatic knee. MRI of the same knee was also performed at the 15- and 30-month followup visits. At the baseline assessment, patients were also weighed, with their shoes removed, on a balance-beam scale, and height was assessed. The institutional review boards of Boston University Medical Center and the Veterans Administration (VA) Boston Health Care System approved the examinations.
All studies were performed with a Signa 1.5T MRI system (General Electric, Milwaukee, WI) using a phased-array knee coil. A positioning device was used to ensure uniformity among patients, with the patient reclining in the supine position, the knee fully extended and immobilized in the knee coil, and the foot perpendicular to the table. Coronal, sagittal, and axial images were obtained. Fat-suppressed fast spin echo (FSE) proton density and T2-weighted images (repetition time 2,200 msec, echo time 20/80 msec) with a slice thickness of 3 mm, a 1-mm interslice gap, 1 excitation, a field of view of 11–12 cm, and a matrix of 256 × 128 pixels were obtained.
Meniscal damage and cartilage morphologic features were assessed using a semiquantitative, multifeature scoring method, the whole-organ magnetic resonance imaging score (WORMS). This method of whole-knee evaluation is applicable for use in conjunction with conventional MRI techniques (14).
Tibiofemoral cartilage on MRI was scored on all 5 plates (central and posterior femur, and anterior, central, and posterior tibia) in both the medial and lateral tibiofemoral joints. The anterior femur was not included in this analysis because this is part of the patellofemoral joint. Scoring was carried out by grading the fat-suppressed T2-weighted FSE images on a 7-point scale, as follows: 0 = normal thickness and signal; 1 = normal thickness but increased signal on T2-weighted images; 2 = partial-thickness focal defect <1 cm in greatest width; 3 = multiple areas of partial-thickness (grade 2) defects intermixed with areas of normal thickness, or a grade 2 defect wider than 1 cm but <75% of the region; 4 = diffuse (≥75% of the region) partial-thickness loss; 5 = multiple areas of full-thickness loss wider than 1 cm but <75% of the region; 6 = diffuse (≥75% of the region) full-thickness loss.
In the WORMS system, grade 1 does not represent a morphologic abnormality, but rather indicates a change in signal in cartilage having otherwise-normal morphologic features. Grades 2 and 3 represent similar types of abnormality of the cartilage, that is, focal defects without overall thinning. Scores of 1 and 2 were exceedingly unusual. Therefore, to create a consistent and logical scale for evaluation of cartilage morphologic change, we collapsed the WORMS values to a new scale of 0–4, where the original WORMS values of 0 and 1 were collapsed to 0, the original scores of 2 and 3 were collapsed to 1, and the original scores of 4, 5, and 6 were considered to be 2, 3, and 4, respectively.
Films were read paired and unblinded to sequence by 2 readers (AG and MG, both of whom are musculoskeletal radiologists) using MRI sequence data from the sagittal and coronal planes. The intraobserver agreement (kappa value) for reading of cartilage morphologic changes ranged from 0.72 to 0.97, and the interobserver agreement was 0.62. We defined a lesion as occurring in either the medial or the lateral compartment if it was present in the femur or the tibia of that compartment. Although we conducted analyses using the collapsed WORMS cartilage scale of 0–4, analyses using the original scale of 0–6 yielded the same results.
The anterior horn, body segment, and posterior horn of each of the medial and lateral menisci were graded from 0 to 4 based on both the sagittal and the coronal images, with 0 = intact menisci, 1 = minor radial tear or parrot-beak tear, 2 = nondisplaced tear or prior surgical repair, 3 = displaced tear or partial resection, and 4 = complete maceration/destruction or complete resection. A tear was defined when there was a signal change within the meniscus that extended to the surface of the meniscus. This global scoring of meniscal integrity incorporates all elements of meniscal disease and also requires incorporation of factors of meniscal position. We therefore considered this to be a global meniscal score, recognizing that abnormal meniscal position represents only one aspect of the total score. For the purposes of this analysis, we refer to this as the meniscal damage score. The interobserver agreement (interclass correlation coefficient [ICC]) for reading of meniscal damage ranged from 0.95 to 0.97. These films were read paired and blinded to sequence. To minimize bias, the reading of meniscal damage was performed independent of the cartilage morphology reading.
Using the coronal MRIs and eFilm Workstation software, we determined the following meniscal position measures, to the nearest millimeter, in both the medial and the lateral compartments: subluxation, meniscal height, and meniscal covering and uncovering of the tibial plateau (see Figure 1). On the coronal sequence, the image in which the medial tibial spine volume was maximal was selected for all readings. On this image, the reference point for measuring the extent of subluxation, tibial width, and amount of coverage was the edge of the tibial plateau without osteophytes (Figure 2). The proportion of coverage was calculated as meniscal covering divided by the sum of meniscal covering and meniscal uncovering. In the sagittal plane, anterior subluxation of the medial and lateral menisci was assessed (Figure 3). A meniscus that was completely macerated or destroyed (as defined above) did not generate a measure of subluxation. Thus, when the WORMS value assigned to the meniscus was equal to a score of 4 (maceration and often absent meniscus), we did not include these knees in analyses of subluxation. Interobserver reliability (ICC values) for reading the measures of meniscal position ranged from 0.86 to 0.93. For all of these analyses, the predictors (meniscal damage and meniscal position) were read at baseline, and the outcome (cartilage morphologic changes) was read at 0, 15, and 30 months.
Figure 2. Representative example of meniscal position measurement in the coronal plane, demonstrating medial meniscal subluxation (M) in the coronal plane (measured from the most subluxed edge of the meniscus to the edge of the medial tibial plateau), uncovering (U) of the tibial plateau (from the meniscus to the medial tibial spine), and reduced height (H) of the meniscus at the edge of the tibial plateau, compared with maximal height of the meniscus.
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Figure 3. Representative example of meniscal position measurement in the sagittal plane, demonstrating anterior medial meniscal subluxation (S) in the sagittal plane (measured from the anterior tibial plateau, excluding osteophytes, to the most subluxed edge of the meniscus anteriorly).
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Cartilage loss (the primary outcome variable) was defined as an increase of at least 1 in the cartilage morphologic score (modified WORMS) over time at any plate, using the compressed scale of 0–4. This primary ordinal outcome (based on the change in score by plate, with a possible range for change of 0–4) was defined in each plate as the change in cartilage score from baseline to followup. Of all the plates assessed, 10.5% in the medial compartment had the maximal cartilage score at baseline, and 4.3% in the lateral compartment had the maximal cartilage score at baseline; the plates with a maximal cartilage score at baseline were excluded from the analysis, but other plates in the same subject were used in the analysis.
We used a proportional odds logistic regression model with generalized estimating equations (GEE) to assess the effect of each predictor (quartiles of the meniscal position factor, and meniscal damage from the baseline assessment, as predictors in each model) on cartilage loss in each of the 5 plates within a compartment (change in cartilage morphologic score from baseline to followup). Models were adjusted for age, sex, body mass index (BMI), and tibial width. Cartilage plates with a maximal score at baseline were not included in the analysis. Statistical analyses were performed using SAS software (release 8.2; SAS Institute, Cary, NC). We also tested the correlation between different measures of meniscal disease and malpositioning, with Spearman's rank correlation coefficients.