OBJECTIVE: The Osteoarthritis Initiative (OAI) is aimed at validating (imaging) biomarkers for monitoring progression of knee OA. Here we analyze regional femorotibial (FT) cartilage thickness changes over 1 year using 3 Tesla MRI. Specifically, we tested whether changes in central subregions exceed those in the total cartilage plates. METHODS: The right knees of a subsample of the OAI progression subcohort (n=156, age 60.9+/-9.9 years) were studied. Fifty-four participants had definite radiographic osteoarthritis (OA) (KLG 2 or 3) and a BMI>30. Mean and minimal cartilage thickness were determined in subregions of the medial/lateral tibia (MT/LT), and of the medial/lateral weight-bearing femoral condyle (cMF/cLF), after paired (baseline, follow up) segmentation of coronal FLASHwe images with blinding to the order of acquisition. RESULTS: The central aspect of cMF displayed a 5.8%/2.8% change in mean thickness in the group of 54/156 participants, respectively, with a standardized response mean (SRM) of -0.47/-0.31, whereas cartilage loss in the total cMF was 4.1%/1.9% (SRM -0.49/-0.30). In the central MT, the rate of change was -1.6%/-0.9% and the SRM -0.29/-0.20, whereas for the entire MT the rate was -1.0%/-0.5% and the SRM -0.21/-0.12. Minimal thickness displayed greater rates of change, but lower SRMs than mean thickness. CONCLUSIONS: This study shows that the rate of cartilage loss is greater in central subregions than in entire FT cartilage plates. The sensitivity to change in central subregions was higher than for the total cartilage plate in the MT and was similar to the total plate in the medial weight-bearing femur.