Predictive Validity of Radiographic Trabecular Bone Texture in Knee Osteoarthritis: The Osteoarthritis Research Society International/Foundation for the National Institutes of Health Osteoarthritis Biomarkers Consortium

Abstract

Objective: To evaluate radiographic subchondral trabecular bone texture (TBT) as a predictor of clinically relevant osteoarthritis (OA) progression (combination of symptom and structural worsening).

Methods: The Foundation for the National Institutes of Health (FNIH) OA Biomarkers Consortium undertook a study of progressive knee OA cases (n = 194 knees with both radiographic and pain progression over 24-48 months) and comparators (n = 406 OA knees not meeting the case definition). TBT parameters were extracted from a medial subchondral tibial region of interest by fractal signature analysis of radiographs using validated semiautomated software. Baseline TBT and time-integrated values over 12 and 24 months were evaluated for association with case status and separately with radiographic and pain progression status, adjusted for age, sex, body mass index, race, baseline Kellgren/Lawrence grade, baseline joint space width, Western Ontario and McMaster Universities Osteoarthritis Index pain score, and pain medication use. C statistics were generated from receiver operating characteristic curves.

Results: Relative to comparators, cases were characterized by thinner vertical and thicker horizontal trabeculae. The summed composite of 3 TBT parameters at baseline and over 12 and 24 months best predicted case status (odds ratios 1.24-1.43). The C statistic for predicting case status using the TBT composite score (0.633-0.649) was improved modestly but statistically significantly over the use of covariates alone (0.608). One TBT parameter, reflecting thickened horizontal trabeculae in cases, at baseline and over 12 and 24 months, predicted risk of any progression (radiographic and/or pain progression).

Conclusion: Although associations are modest, TBT could be an attractive means of enriching OA trials for progressors since it can be generated from screening knee radiographs already standard in knee OA clinical trials.

Figure 1. Graphic representation of fractal signature curves at baseline, 12M and 24M

Fractal signature curves are generated by plotting the fractal dimension (FD on the y axis) versus the radius (x axis). FD and radius generated from the horizontal filter of the KneeAnalyzer software yield information about the vertical trabeculae (panels A–C); curves derived from the vertical filter yield information about the horizontal trabeculae (panels D–F). The line graphs plot mean (raw unadjusted) data on subjects with observations at all 3 time points at baseline (panels A, D), 12 months (panels B, E) and 24 months (panels C, F). Orange lines depict the mean fractal signature curves for primary cases (knee osteoarthritis subjects with radiographic and pain progression from 24–48 months after baseline); blue lines depict the mean fractal signature curves for primary comparators (subjects with knee osteoarthritis but not meeting the primary case definition).