In this study, we propose a novel framework that utilizes deep learning (DL) and attention mechanisms to predict the radiographic progression of patellofemoral osteoarthritis (PFOA) over a period of seven years. This study included subjects (1832 subjects, 3276 knees) from the baseline of the MOST study. PF joint regions-of-interest were identified using an automated landmark detection tool (BoneFinder) on lateral knee X-rays. An end-to-end DL method was developed for predicting PFOA progression based on imaging data in a 5-fold cross-validation setting. A set of baselines based on known risk factors were developed and analyzed using gradient boosting machine (GBM). Risk factors included age, sex, BMI and WOMAC score, and the radiographic osteoarthritis stage of the tibiofemoral joint (KL score). Finally, we trained an ensemble model using both imaging and clinical data. Among the individual models, the performance of our deep convolutional neural network attention model achieved the best performance with an AUC of 0.856 and AP of 0.431; slightly outperforming the deep learning approach without attention (AUC=0.832, AP= 0.4) and the best performing reference GBM model (AUC=0.767, AP= 0.334). The inclusion of imaging data and clinical variables in an ensemble model allowed statistically more powerful prediction of PFOA progression (AUC = 0.865, AP=0.447), although the clinical significance of this minor performance gain remains unknown. This study demonstrated the potential of machine learning models to predict the progression of PFOA using imaging and clinical variables. These models could be used to identify patients who are at high risk of progression and prioritize them for new treatments. However, even though the accuracy of the models were excellent in this study using the MOST dataset, they should be still validated using external patient cohorts in the future.

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