Joint space narrowing and Kellgren-Lawrence progression in knee osteoarthritis: an analytic literature synthesis

Abstract

Objective: While the interpretation of cartilage findings on magnetic resonance imaging (MRI) evolves, plain radiography remains the standard method for assessing progression of knee osteoarthritis (OA). We sought to describe factors that explain variability in published estimates of radiographic progression in knee OA.

Design: We searched PubMed between January 1985 and October 2006 to identify studies that assessed radiographic progression using either joint space narrowing (JSN) or the Kellgren-Lawrence (K-L) scale. We extracted cohort characteristics [age, gender, and body mass index (BMI)] and technical and other study factors (radiographic approach, study design, OA-related cohort composition). We performed meta-regression analyses of the effects of these variables on both JSN and K-L progression.

Results: Of 239 manuscripts identified, 34 met inclusion criteria. The mean estimated annual JSN rate was 0.13 +/- 0.15 mm/year. While we found no significant association between JSN and radiographic approach among observational studies, full extension was associated with greater estimated JSN among randomized control trials (RCTs). Overall, observational studies that used the semi-flexed approach reported greater JSN than RCTs that used the same approach. The overall mean risk of K-L progression by at least one grade was 5.6 +/- 4.9%, with higher risk associated with shorter study duration, OA definition (K-L > or = 2 vs K-L > or = 1) and cohorts composed of subjects with both incident and prevalent OA.

Conclusion: While radiographic approach and study design were associated with JSN, OA definition, cohort composition and study duration were associated with risk of K-L progression. These findings may inform the design of disease modifying osteoarthritis drug (DMOAD) trials and assist clinicians in optimal timing of OA treatments.

Figure 1

Manuscript search and selection process.

Figure 2

Annual joint space narrowing stratified by study design and radiographic approach. Circles represent individual mean joint space narrowing estimates. Circle area is proportional to sample size of corresponding cohort. Means within study design and radiographic approach sub-categories are depicted in grey. Overall means within each study design category and the overall mean for all estimates are depicted in black. The means are displayed above corresponding circles, with error bars representing 95% confidence intervals. Each study reference is denoted next the circle, representing the corresponding manuscript from which the progression estimate was derived. An estimate of 0.7 mm/year (RCT, full extension) is not shown for scaling purposes.

Figure 3

Annual risk of Kellgren-Lawrence progression stratified by cohort composition. Circles represent individual estimates of the proportion of the cohort that progressed by at least one Kellgren-Lawrence grade per year of follow-up time. Circle area is proportional to sample size of corresponding cohort. Means within each cohort composition category are depicted in grey. Overall mean for all reviewed Kellgren-Lawrence studies is depicted in black. The means are displayed above corresponding circles, with error bars representing 95% confidence intervals. Each study reference is denoted next the circle, representing the corresponding manuscript from which the progression estimate was derived.

Figure 4

Association of OA progression (joint space narrowing (4A) and Kellgren-Lawrence (4B)) and study duration. Circles represent individual estimates of the proportion of the cohort that progressed by at least one Kellgren-Lawrence grade per year of follow-up time. Circle area is proportional to sample size of corresponding cohort. Regression line for follow-up time is weighted for sample size and adjusted for radiographic approach (4A and 4B), OA definition (4B), and cohort composition (4B).