Objective. By magnetic resonance imaging (MRI), subchondral bone attrition (SBA) can be seen in early osteoarthritis (OA), but the significance of this is unknown. We therefore evaluated whether SBA was associated with cartilage loss within the same subregion of the knee. Methods. The Multicenter Osteoarthritis Study is a cohort of individuals who have or are at high risk for knee OA. At baseline and 30 months, participants' knee MRIs were graded using the Whole-Organ Magnetic Resonance Imaging Score in the 10 subregions of the tibiofemoral joint for cartilage morphology and SBA. We conducted analyses within a knee to eliminate between-person confounding, using an M:N (cases:controls) matched case-control approach with the 10 subregions of a person's knee forming a matched set. Cases within a knee were defined as subregions with cartilage loss, while controls were subregions in that same knee without cartilage loss. We evaluated the association of cartilage loss over 30 months with the presence of baseline SBA in the same subregion within that knee using conditional logistic regression. Results. SBA was associated with an odds ratio of 7.5 (95% confidence interval 5.6 -9.9, P < 0.0001) for cartilage loss in the same subregion compared with subregions without any baseline SBA in our sample of 459 knees from participants, 64% of whom were women, with a mean age of 63 years and a mean body mass index of 30.5 kg/m 2. Conclusion. SBA is strongly associated with cartilage loss within the same subregion of a knee. SBA may directly influence overlying cartilage loss or serve as a marker of an area undergoing great compressive stress and in which cartilage loss is inevitable. © 2009, American College of Rheumatology.