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Abstract

  1. Top of page
  2. Abstract
  3. PATIENTS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. Acknowledgements
  7. REFERENCES

Objective

To explore the relative contribution of hyaline cartilage morphologic features and the meniscus to the radiographic joint space.

Methods

The Boston Osteoarthritis of the Knee Study is a natural history study of symptomatic knee osteoarthritis (OA). Baseline and 30-month followup assessments included knee magnetic resonance imaging (MRI) and fluoroscopically positioned weight-bearing knee radiographs. Cartilage and meniscal degeneration were scored on MRI in the medial and lateral tibiofemoral joints using a semiquantitative grading system. Meniscal position was measured to the nearest millimeter. The dependent variable was joint space narrowing (JSN) on the plain radiograph (possible range 0–3). The predictor variables were MRI cartilage score, meniscal degeneration, and meniscal position measures. We first conducted a cross-sectional analysis using multivariate regression to determine the relative contribution of meniscal factors and cartilage morphologic features to JSN, adjusting for body mass index (BMI), age, and sex. The same approach was used for change in JSN and change in predictor variables.

Results

We evaluated 264 study participants with knee OA (mean age 66.7 years, 59% men, mean BMI 31.4 kg/m2). The results from the models demonstrated that meniscal position and meniscal degeneration each contributed to prediction of JSN, in addition to the contribution by cartilage morphologic features. For change in medial joint space, both change in meniscal position and change in articular cartilage score contributed substantially to narrowing of the joint space.

Conclusion

The meniscus (both its position and degeneration) accounts for a substantial proportion of the variance explained in JSN, and the change in meniscal position accounts for a substantial proportion of change in JSN.

Osteoarthritis (OA) is a significant public health challenge, being ranked as the leading cause of disability in the elderly (1). Recent estimates suggest that symptomatic knee OA occurs in 13% of individuals ages ≥60 years (2). Although this prevalence is high, it is expected to increase even more as the US population ages. Despite its growing prevalence, few effective therapies exist that can modify the course of the disease. One major impediment to the development of treatments that would delay structural deterioration has been the lack of a sensitive, reproducible, and easily assessed measure of OA outcomes.

There are currently a number of methods used to measure morphologic changes in the joint. Frequently, the structural consequences of OA of the knee are monitored by determining joint space narrowing (JSN) on weight-bearing radiographs; however, the reliability of this method is greatly dependent on subject positioning, and the information provided is limited to 2 dimensions (3–6).

Loss of joint space on plain radiographs has been equated with loss of hyaline articular cartilage, in clinical trials of OA. However, hyaline articular cartilage is not the only structure occupying the joint space on plain radiographs, since this space is shared with the meniscus (6). As a result, studies have suggested that the initial JSN viewed on conventional radiographs is often secondary to meniscal extrusion rather than thinning of articular cartilage (7, 8). The contribution of meniscal disease or meniscal position to longitudinal loss of joint space as evidenced on the radiograph is unknown, but if much of the joint space loss were attributable to meniscal disease, this would cast considerable doubt on the notion that joint space loss is a reflection of hyaline cartilage loss.

Magnetic resonance imaging (MRI) is being developed as a method to assess joint morphologic changes in knee OA, with the goal of providing a sensitive, noninvasive tool for the study of healthy and diseased states and a means of assessing risk factors and the effectiveness of therapeutic interventions for prevention of pain, dysfunction, and disability in OA. MRI provides the opportunity to ascertain directly the structure of hyaline articular cartilage as well as the meniscus. Using MRI and radiography, we examined the relative contributions of hyaline cartilage loss and both position and degeneration of the meniscus to changes in the radiographic joint space, in cross-sectional and longitudinal analyses.

PATIENTS AND METHODS

  1. Top of page
  2. Abstract
  3. PATIENTS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. Acknowledgements
  7. REFERENCES

Study population.

Patients were recruited to participate in a natural history study of symptomatic knee OA, the Boston Osteoarthritis of the Knee Study (conducted from 1997 to 2001). The recruitment for this study has been described in detail elsewhere (9). Briefly, participants were recruited from 2 prospective studies, 1 of men and 1 of women. 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. A series of knee radiographs (posteroanterior, lateral, and skyline) were obtained from each patient to determine whether radiographic OA was present. If patients had a definite osteophyte on any view of the symptomatic knee, they were eligible for the study. Because they had frequent knee symptoms and radiographically defined OA, all patients met the American College of Rheumatology criteria for symptomatic knee OA (10).

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 an MRI of the more symptomatic knee. MRIs of the same knee were also performed at the 15- and 30-month followup visits. At the baseline assessment, patients were weighed, with shoes off, on a balance-beam scale, and height was assessed. The Institutional Review Boards of Boston University Medical Center and the Veterans Administration Boston Health Care System approved the examinations.

MRI measurements.

All studies were performed with a Signa 1.5T MRI system (General Electric, Milwaukee, WI) using a phased-array, 2-element surface-receiver knee coil. A positioning device was used to ensure uniformity among patients and, over time, in individual patients. Coronal, sagittal, and axial images were obtained. Fat-suppressed spin-echo (FSE) proton density and T2-weighted images (repetition time 2,200 msec, echo time 20/80 msec, slice thickness 3 mm, 1-mm interslice gap, 1 excitation, field of view 11–12 cm, matrix 256 × 128 pixels) were obtained.

Meniscal degeneration and cartilage morphologic changes were assessed using the semiquantitative, multifeature Whole-Organ MRI Score (WORMS), which is applicable for use with conventional MRI techniques (11), and readers were blinded to these scores of MRI progression. There were a total of 3 readers who scored all MRIs, as previously described (12). The majority of longitudinal MRIs (86%) were read by a trained musculoskeletal radiologist (AG) and a musculoskeletal researcher, who read the images together. One reader (DJH), who was trained in the WORMS method by one of the musculoskeletal radiology readers (AG), scored the remainder of the subjects' MRIs. Thirty MRIs of the knee were reread during the course of the study for ascertainment of the intra- and interobserver reliability of the scoring of cartilage morphologic changes. Ten films were reread during the course of the study to ascertain the reliability of the scoring of other features, including features of the meniscus.

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 the lateral tibiofemoral joints. The anterior femur was not included in this analysis because this is part of the patellofemoral joint. Plates of the tibiofemoral joint were read using the coronal and sagittal fat-suppressed T2-weighted FSE images on a 7-point scale: 0 = normal thickness and signal; 1 = normal thickness but increased signal on T2-weighted images; 2 = partial-thickness focal defect of <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, a score of 1 does not represent a morphologic abnormality but rather a change in signal in cartilage with otherwise normal morphologic features. Scores of 2 and 3 represent similar types of abnormality of the cartilage, focal defects without overall thinning. Scores of 1 and 2 in this population were exceedingly unusual. Therefore, to create a consistent and logical scale for evaluation of cartilage morphologic change and a fair comparison with radiographic JSN changes, we collapsed the WORMS cartilage scores to a 0–4 scale, in which the original scores 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 2, 3, and 4, respectively (12). The intraclass correlation coefficient (ICC) for agreement of cartilage readings among the readers ranged from 0.72 to 0.97. 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 this collapsed WORMS cartilage scale, analyses using the original scale yielded similar 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: 0 = intact; 1 = minor radial tear or parrot-beak tear; 2 = nondisplaced tear; 3 = displaced tear or partial resection; 4 = complete maceration/destruction or complete resection. This global variable scoring of meniscal integrity incorporates all elements of meniscal disease, and necessarily factors in meniscal position. Herein we regarded this as a global meniscal score, recognizing that abnormal meniscal position represents only one aspect of the score. For the purposes of this analysis, we have described this variable as meniscal degeneration. The interobserver agreement (ICC values) for reading of meniscal degeneration ranged from 0.72 to 0.97.

Using the coronal MR images and EFilm workstation software, we measured the following meniscal position variables 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). These measures were determined on the mid-coronal slice, where the medial tibial spine was of maximal volume. The point of reference for subluxation was the tibial plateau osteochondral junction at the joint margin (excluding osteophytes). Covering was measured from this point to the central edge of the meniscus, and uncovering was measured from this point to the tibial spine, both in the medial and in the lateral tibiofemoral compartments. The proportion of tibial coverage was defined as (meniscal covering/[meniscal covering + meniscal uncovering]).

thumbnail image

Figure 1. Meniscal position measurements obtained on coronal magnetic resonance imaging (MRI). Measurements were made on the mid-coronal slice where the medial tibial spine was of maximal volume. The point of reference for subluxation was the tibial plateau osteochondral junction at the joint margin (excluding osteophytes). Covering was measured from this point to the central edge of the meniscus, and uncovering was measured from this point to the tibial spine (S) for the medial (M) and the lateral (L) tibiofemoral compartments.

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In the sagittal plane, anterior subluxation of the medial and lateral menisci was assessed on 1 sagittal slice for the medial and then the lateral compartment. The slice selected for the medial compartment was located in the area where the semimembranosus tendon was most clearly visible, and for the lateral compartment, the point at which the fibula head was of maximal volume. A meniscus that was completely macerated or destroyed (as defined above) did not generate a measure of subluxation. Thus, when the meniscal WORMS value was equal to 4, we did not include these knees in the analyses of subluxation. Interobserver reliability (ICC values) for readings of meniscal position ranged from 0.86 to 0.93.

For these analyses, the predictors (meniscal degeneration, meniscal position, and cartilage morphologic changes) were read at baseline and 30 months. In addition, the dependent variable, JSN, was determined at both time points.

Radiography.

Weight-bearing posteroanterior radiographs were obtained at 0, 15, and 30 months, using the protocol of Buckland-Wright (13). The beam was aligned relative to the center of the knee using fluoroscopic positioning, and the knee was flexed so that the anterior and posterior lips of the medial tibial plateau were superimposed. The feet were rotated until the tibial spines were centered in the notch, and outlines of foot rotation were then made on foot maps so that the foot rotation would be the same for subsequent films. Fluoroscopic positioning has been shown to produce a more accurate assessment of the joint space compared with nonfluoroscopic acquisition, and to improve reproducibility of the joint space assessment (3). A reader unfamiliar with the MRI findings read all of the radiographs, paired and unblinded to sequence (9).

For evaluation of disease progression, we focused on the width of the joint space in the medial and lateral compartments, since this has been found to correlate with cartilage thickness (6). Films were read by using the Osteoarthritis Research Society International Atlas (14), in which each medial and lateral tibiofemoral joint space was graded from 0 (normal) to 3 (bone on bone). The intraobserver agreement (kappa value) for reading change in JSN was 0.81 (P < 0.001).

Statistical analysis.

All analyses were performed in a compartment-specific manner. The dependent variable was JSN on plain radiographs (possible grade range 0–3). For the predictors, we used the summary score for cartilage in 5 plates (anterior tibia, central tibia, posterior tibia, central femur, and posterior femur; possible range 0–20), the summary score for meniscal degeneration (anterior, body, and posterior; possible range 0–12), and the meniscal subluxation measures by compartment. We described the distribution of each predictor (cartilage score on MRI, semiquantitative score of meniscal morphologic abnormalities, and meniscal subluxation measures) according to radiographic JSN outcome categories. Meniscal coverage was not included in this analysis, because there was no prior knowledge about what is normal and what is abnormal.

We conducted a cross-sectional analysis using a multivariate logistic regression model to estimate the relative contribution of meniscal factors and cartilage morphologic abnormalities to JSN (dependent variable), while adjusting for age, sex, and body mass index (BMI). We used the same approach for change in JSN (dependent variable) and change in predictor variables.

To ensure that we could estimate the relative contributions of each of the meniscal and hyaline cartilage measures to joint space width and loss, we used forced inclusion methods, starting with a model containing age, sex, and BMI and then, one at a time, adding the predictor variables (summary cartilage score on MRI, summary semiquantitative score of meniscal morphologic abnormalities, and meniscal subluxation measures). We also performed regression modeling with initial inclusion of all of the predictor variables, i.e., age, sex, BMI, summary cartilage score on MRI, summary semiquantitative score of meniscal morphologic abnormalities, and meniscal subluxation measures (hereafter referred to as the full model).

We compared the Akaike's information criterion (AIC) and the c statistic (area under the receiver operating characteristic curve [AUC]) generated from the full model with the values generated from the model containing only age, sex, BMI, and each predictor, to assess the relative contribution of each factor to the model. The AIC statistic adds twice the number of predictors and outcome levels to the −2 log likelihood to penalize models that are overly complex, thus arriving at a less biased assessment of the ability of a model to predict the outcome. When comparing models on the basis of the AIC, a lower value indicates a more desirable model (15). The c statistic is the AUC for a model and is a rank-based measure of how well a model discriminates between outcomes. It varies from 0.5 if the model's predictions are no better than chance, to 1.0 when the model always assigns higher probabilities to correct cases than to incorrect cases.

RESULTS

  1. Top of page
  2. Abstract
  3. PATIENTS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. Acknowledgements
  7. REFERENCES

The characteristics of the 264 study participants are presented in Table 1. The mean age was 66.7 years (SD 9.2 years), 59% were men (reflecting the Veterans Administration population from which many of the subjects were drawn), and the average BMI was 31.4 kg/m2 (SD 5.7). Almost 77% of knees had a Kellgren/Lawrence (K/L) radiographic severity grade ≥2 (those with K/L grades <2 had patellofemoral OA) (16).

Table 1. Characteristics and features of the knee joint on radiography and magnetic resonance imaging in the study population (n = 264)*
  • *

    Except where indicated otherwise, values are the mean ± SD (range). Joint space narrowing (JSN) was scored 0–3 on weight-bearing posteroanterior radiographs. BMI = body mass index; K/L = Kellgren/ Lawrence; TF = tibiofemoral.

  • The cartilage morphologic score is the modified Whole-Organ Magnetic Resonance Imaging Score for 5 plates (scale 0–4; summary score range 0–20).

Age, years66.7 ± 9.2 (47–93)
Sex, % male59.1
BMI, kg/m231.4 ± 5.7 (21.4–59.7)
K/L grade ≥2, %76.5
Knees with medial JSN >0 at baseline, %54.6
Knees with lateral JSN >0 at baseline, %13.3
Knees with change in medial JSN, %15.4
Meniscal position 
 Medial meniscus 
  Coronal subluxation, mm 
   Baseline4.8 ± 2.9 (0–17)
   Change0.3 ± 2.3 (−13 to 6)
  Proportion of coverage (range 0–1) 
   Baseline0.19 ± 0.19 (0–0.86)
   Change−0.04 ± 0.14 (−0.55 to 0.49)
  Anterior (sagittal) subluxation, mm 
   Baseline5.6 ± 3.3 (0–17)
   Change0.04 ± 2.4 (−6 to 8)
 Lateral meniscus 
  Coronal subluxation, mm 
   Baseline1.6 ± 2.0 (0–9)
   Change0.01 ± 1.7 (−6 to 9)
  Proportion of coverage (range 0–1) 
   Baseline0.30 ± 0.15 (0–1.0)
   Change−0.03 ± 0.15 (−0.79 to 0.81)
  Anterior (sagittal) subluxation, mm 
   Baseline1.9 ± 3.2 (0–16)
   Change−0.3 ± 2.4 (−12 to 6)
Meniscal degeneration (possible range 0–12) 
 Medial meniscus 
  Baseline3.8 ± 3.8 (0–12)
  Change0.1 ± 0.5 (−2 to 3)
 Lateral meniscus 
  Baseline1.8 ± 3.3 (0–12)
  Change0.1 ± 0.3 (0 to 3)
Cartilage 
 Medial TF compartment 
  Baseline score1.5 ± 1.2
  Subjects with baseline score >0, %85.8
  Increase in score from baseline to followup0.2 ± 0.4
 Lateral TF compartment 
  Baseline score0.7 ± 1.0
  Subjects with baseline score >0, %63.5
  Increase in score from baseline to followup0.1 ± 0.2

Contingency analyses (Table 2) allowed us to assess the prevalence of abnormal values for each predictor, both in cross-sectional analyses and in analyses of change in predictors in relation to change in JSN. The results demonstrated that with a JSN grade >0, morphologic abnormalities in cartilage and in meniscal position were almost universal, suggesting parallel degenerative processes in these structures. The proportion of participants with different JSN grades and the change in these grades over 30 months of followup are shown in Table 3.

Table 2. Distribution of subjects with structural features of interest in relation to categories of joint space narrowing (JSN)*
 Medial meniscal subluxation (anterior or coronal) change >0 mmMedial TF cartilage score >0 (mean of 5 plates)Medial meniscal degeneration score >0
  • *

    Values are the percent of patients. TF = tibiofemoral.

Cross-sectional   
 Medial TF joint   
  JSN grade 0 (n = 120)98.371.634.2
  JSN grade >0 (n = 144)100.097.889.1
 Lateral TF joint   
  JSN grade 0 (n = 229)64.557.925.2
  JSN grade >0 (n = 35)100.0100.088.6
Longitudinal (medial only)   
 JSN change 0 (n = 147)84.339.56.2
 JSN change >0 (n = 33)90.369.79.4
Table 3. Changes in JSN grades from baseline to followup*
 Medial JSNLateral JSN
  • *

    Values are the number (%) of patients in each grade category of joint space narrowing (JSN) (n = 264 at baseline; n = 216 at followup).

  • Change defined as missing in this group.

Baseline JSN grade  
 0120 (45.5)229 (86.7)
 143 (16.3)14 (5.3)
 260 (22.7)15 (5.7)
 341 (15.5)6 (2.3)
Change in JSN grade from baseline to followup  
 −14 (2.2)1 (0.5)
 0143 (79.4)193 (91.5)
 128 (15.6)15 (7.1)
 25 (2.8)2 (1.0)
 Baseline JSN grade 3365

The results of the regression models, which included the predictor variables (summary cartilage score on MRI, summary semiquantitative score of meniscal morphologic abnormalities, and meniscal subluxation measures), provide a reflection of the individual contribution of each of these factors to the dependent variable, JSN (see Table 4 [association with medial JSN and lateral JSN] and Table 5 [association with change in medial JSN]). Change in lateral JSN was not examined because the changes in this feature occurred in too few knees (7 participants) to generate valid models.

Table 4. Assessment of cross-sectional association between JSN and predictors*
ModelDegrees of freedomAICChange in AIC from basic modelc statisticChange in c statistic from basic model
  • *

    The cross-sectional association (R2) between medial joint space narrowing (JSN) and predictors in the full model was 0.73, and for lateral JSN and predictors in the full model, R2 = 0.80. AIC = Aikake's information criterion; BMI = body mass index.

Medial JSN and predictors     
 Basic model (age, sex, BMI)3294.80.63
 Basic model + 3 meniscal position variables6164.1130.60.930.30
 Basic model + cartilage4177.1117.70.900.27
 Basic model + meniscal degeneration4211.283.50.860.23
 Full model (all factors)8145.7149.10.950.32
Lateral JSN and predictors     
 Basic model (age, sex, BMI)3128.200.650
 Basic model + 3 meniscal position variables666.961.30.970.32
 Basic model + cartilage454.174.10.960.31
 Basic model + meniscal degeneration469.958.40.920.27
 Full model (all factors)849.678.60.990.34
Table 5. Assessment of change in medial JSN and change in predictors (n = 180)*
ModelDegrees of freedomAICChange in AIC from basic modelc statisticChange in c statistic from basic model
  • *

    The longitudinal association (R2) of change in medial JSN with change in predictors in the full model was 0.25. See Table 4 for definitions.

Basic model (age, sex, BMI)3173.90.64
Basic model + 3 meniscal position variables6138.135.80.710.07
Basic model + cartilage4165.28.70.740.10
Basic model + meniscal degeneration4171.52.40.640.00
Full model (all factors)8132.741.20.790.15

The results from these models demonstrated that meniscal position and meniscal degeneration each contributed greatly to the change in the AUC (c statistic) and the change in the AIC for the models predicting JSN. With regard to the change in medial joint space, both change in meniscal position and change in articular cartilage score contributed substantially to narrowing of the joint space over 30 months, as assessed using the AIC and c statistic criteria, whereas the change in meniscal degeneration score did not contribute substantially to joint space loss. Some representative examples of the contribution of meniscal abnormality to joint space in the knee are demonstrated in Figures 2A (meniscal degeneration) and 2B (meniscal position).

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Figure 2. Representative examples of the contribution of meniscal pathologic abnormalities to change in joint space narrowing (JSN). A, Change in JSN from grade 0 to grade 1 on plain radiograph at 30 months of followup (blue arrow indicates compartment with JSN). During the same interval the hyaline articular cartilage has remained much the same and the medial meniscus is now completely macerated (yellow arrow indicates the previous location of the meniscus). B, Change in medial compartment JSN from grade 0 to grade 2 on plain radiograph at 30 months of followup (blue arrow). During the same interval the hyaline articular cartilage has remained much the same and the medial meniscus is now subluxed/displaced medially out of the joint space (yellow arrow).

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DISCUSSION

  1. Top of page
  2. Abstract
  3. PATIENTS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. Acknowledgements
  7. REFERENCES

Features of the meniscus (position and degeneration) account for a substantial proportion of the explained variance in JSN, and change in meniscal position accounts for a substantial proportion of change in JSN. Previously held beliefs that ascertainment of JSN and its change are a reflection only of damage to hyaline articular cartilage need to be reconsidered. Based on the results presented herein, a large contribution to the variance in JSN is explained by alterations in the meniscus.

Previous studies have demonstrated that hyaline articular cartilage is not the only structure occupying the joint space on plain radiographs; this space is shared with the meniscus (6). Buckland-Wright et al (6) measured joint space width from weight-bearing plain-film macroradiographs obtained in the tunnel view and compared this with the sum of femoral and tibial cartilage thicknesses measured from double-contrast macroarthrograms of the same regions of the same knees obtained in the non–weight-bearing lateral position in 20 persons with knee OA. Comparison of the joint space width with the sum of the tibial and femoral cartilage thicknesses revealed a significant correlation between the 2 measurements in the medial, but not the lateral, compartment. We also have demonstrated that cartilage on MRI is correlated with JSN on radiographs (12) but have not examined the relative contributions of meniscus and cartilage to joint space loss.

Similarly, some study findings have suggested that the initial JSN on conventional radiographs is secondary to meniscal extrusion rather than thinning of articular cartilage (7, 8). These cross-sectional studies investigated the association between meniscal subluxation and JSN and demonstrated that, indeed, subluxation does contribute to JSN.

The structural alterations that form the OA disease process are markedly collinear, that is, as hyaline articular cartilage becomes more morphologically abnormal, the other structural processes parallel these changes, with increasing degenerative findings in the meniscus and increasing meniscal displacement. Thus, the causal process is complex and joint space loss genuinely reflects changes in all of these structures, although hyaline articular cartilage loss in some knees (see, for example, Figure 2) is less important as a cause than meniscal variables.

It appears that there may be some discordance between the cross-sectional and longitudinal contribution of meniscal degeneration to each model as presented herein. We believe the likely explanation for this apparent discordance is that meniscal degeneration was frequently abnormal (i.e., score >0) in the cross-sectional model, whereas this variable did not change frequently when compared with cartilage or meniscal position (the proportion of subjects with change in each of these variables is displayed in Table 2). There are 2 potential explanations for this. One is that incidence/progression of meniscal degeneration may have been infrequent over the interval studied, or alternatively, the meniscal degeneration scoring system may not have been responsive enough to detect this change if it were to occur.

There are a number of study limitations that warrant mentioning. The model for the change in lateral joint space had such small numbers that the estimates were unstable (results not shown). In contrast to the cross-sectional evaluation, in which a large proportion of the variance was explained by the model, the variance explained (R2 value) for change in medial JSN was only 0.25, suggesting that most of the variability in medial JSN change remains unexplained.

Optimally, we would have performed the analyses using the continuous joint space width measurement. This is not optimal for assessing the lateral joint space, and in this study, most of the variability in medial continuous joint space width was seen in persons with a relatively normal joint space width, and may reflect pseudo-widening and/or changes in participant positioning.

The present analyses were based on observer-dependent measures of structure. JSN on the radiograph and both meniscal degeneration and cartilage abnormalities on MRI are semiquantitative measures, whereas meniscal position measures are continuous measures. The reproducibility for each of these measures was good to excellent; however, this does not eliminate the potential for misclassification. Furthermore, because meniscal position is a continuous measure, this may provide a more precise estimate of its contribution, whereas the other variables, which have a finite number of options, may lack that same level of precision.

The findings suggest that the meniscus contributes a large proportion to the joint space and its change. This has important implications for trials testing OA disease-modifying treatments. For example, if a product has been developed with the express intent of preserving hyaline articular cartilage, we would advocate measuring the hyaline articular cartilage directly, or at least recognizing that when measuring JSN, other factors such as the meniscus can affect the variability of this outcome. Currently, the major structural end point for trials of structure-modifying agents is the radiographic joint space. Our data would suggest that if change in hyaline articular cartilage is the outcome of interest, it should be noted that a large proportion of the variance in joint space change is made up of change in the meniscus. Careful consideration of the likely tissue target for new pharmacologic interventions and the method of measurement for this tissue target need to be ascertained before accepting a measurement end-point technique that may not be optimal.

Acknowledgements

  1. Top of page
  2. Abstract
  3. PATIENTS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. Acknowledgements
  7. REFERENCES

We would like to thank the participants and staff of the Boston Osteoarthritis Knee Study. We also thank the staff at the Osteoporosis and Arthritis Research Group, where the MRI readings occurred, in particular, John Lynch, Jing Li, and Mikayel Grigorian.

REFERENCES

  1. Top of page
  2. Abstract
  3. PATIENTS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. Acknowledgements
  7. REFERENCES
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