Towards understanding mechanistic subgroups of osteoarthritis: 8-year cartilage thickness trajectory analysis

Abstract

Many studies have validated cartilage thickness as a biomarker for knee osteoarthritis (OA); however, few studies investigate beyond cross-sectional observations or comparisons across two timepoints. By characterizing the trajectory of cartilage thickness changes over 8 years in healthy individuals from the OA initiative data set, this study discovers associations between the dynamics of cartilage changes and OA incidence. A fully automated cartilage segmentation and thickness measurement method were developed and validated against manual measurements: mean absolute error = 0.11–0.14 mm (n = 4129 knees) and automatic reproducibility = 0.04–0.07 mm (n = 316 knees). The mean thickness for the medial and lateral tibia (MT, LT), central weight-bearing medial and lateral femur (cMF, cLF), and patella (P) cartilage compartments were quantified for 1453 knees at seven timepoints. Trajectory subgroups were defined per cartilage compartment such as stable, thinning to thickening, accelerated thickening, plateaued thickening, thickening to thinning, accelerated thinning, or plateaued thinning. For tibiofemoral compartments, the stable (22%–36%) and plateaued thinning (22%–37%) trajectories were the most common, with an average initial velocity (μm/month), acceleration (μm/month2) for the plateaued thinning trajectories LT: −2.66, 0.0326; MT: −2.49, 0.0365; cMF: −3.51, 0.0509; and cLF: −2.68, 0.041. In the patella compartment, the plateaued thinning (35%) and thickening to thinning (24%) trajectories were the most common, with an average initial velocity, acceleration for each −4.17, 0.0424; 1.95, −0.0835. Knees with nonstable trajectories had higher adjusted odds of OA incidence than stable trajectories: accelerated thickening, accelerated thinning, and plateaued thinning trajectories of the MT had adjusted odds ratio (OR) of 18.9, 5.48, and 1.47, respectively; in the cMF, adjusted OR of 8.55, 10.1, and 2.61, respectively.