Objective. To develop a system for predicting the progression of radiographic knee osteoarthritis (OA) using tibial trabecular bone texture.Methods. We studied 203 knees with (n ؍ 68) or without (n ؍ 135) radiographic tibiofemoral OA in 105 subjects (90 men and 15 women with a mean age of 54 years) in whom 2 sets of knee radiographs were obtained 4 years apart. We determined medial and lateral compartment tibial trabecular bone texture using an automated region selection method. Three texture parameters were calculated: roughness, degree of anisotropy, and direction of anisotropy based on a signature dissimilarity measure method. We evaluated tibiofemoral OA progression using a radiographic semiquantitative outcome: an increase in the medial joint space narrowing (JSN) grade. We examined the predictive ability of trabecular bone texture in knees with and those without preexisting radiographic OA, with adjustment for age, sex, and body mass index, using logistic regression (generalized estimating equations) and receiver operating characteristic curves.Results. The prediction of increased medial JSN in knees with or without preexisting radiographic OA was the most accurate for medial trabecular bone texture; the area under the curve (AUC) was 0.77 and 0.75, respectively. For lateral trabecular bone texture, the AUC was 0.71 in knees with preexisting OA and 0.72 in knees without preexisting OA.Conclusion. We have developed a system, based on analyzing tibial trabecular bone texture, which yields good prediction of loss of tibiofemoral joint space. The predictive ability of the system needs to be further validated.