BACKGROUND: Osteoporotic vertebral fractures (OVFs) are common in older adults and often lead to disability if not properly diagnosed and classified. With the increased use of computed tomography (CT) imaging and the development of radiomics and deep learning technologies, there is potential to improve the classification accuracy of OVFs. OBJECTIVE: This study aims to evaluate the efficacy of a deep learning radiomics model, derived from CT imaging, in accurately classifying OVFs. METHODS: The study analyzed 981 patients (aged 50-95 years; 687 women, 294 men), involving 1098 vertebrae, from 3 medical centers who underwent both CT and magnetic resonance imaging examinations. The Assessment System of Thoracolumbar Osteoporotic Fractures (ASTLOF) classified OVFs into Classes 0, 1, and 2. The data were categorized into 4 cohorts: training (n=750), internal validation (n=187), external validation (n=110), and prospective validation (n=51). Deep transfer learning used the ResNet-50 architecture, pretrained on RadImageNet and ImageNet, to extract imaging features. Deep transfer learning-based features were combined with radiomics features and refined using Least Absolute Shrinkage and Selection Operator (LASSO) regression. The performance of 8 machine learning classifiers for OVF classification was assessed using receiver operating characteristic metrics and the "One-vs-Rest" approach. Performance comparisons between RadImageNet- and ImageNet-based models were performed using the DeLong test. Shapley Additive Explanations (SHAP) analysis was used to interpret feature importance and the predictive rationale of the optimal fusion model. RESULTS: Feature selection and fusion yielded 33 and 54 fused features for the RadImageNet- and ImageNet-based models, respectively, following pretraining on the training set. The best-performing machine learning algorithms for these 2 deep learning radiomics models were the multilayer perceptron and Light Gradient Boosting Machine (LightGBM). The macro-average area under the curve (AUC) values for the fused models based on RadImageNet and ImageNet were 0.934 and 0.996, respectively, with DeLong test showing no statistically significant difference (P=2.34). The RadImageNet-based model significantly surpassed the ImageNet-based model across internal, external, and prospective validation sets, with macro-average AUCs of 0.837 versus 0.648, 0.773 versus 0.633, and 0.852 versus 0.648, respectively (P<.05). Using the binary "One-vs-Rest" approach, the RadImageNet-based fused model achieved superior predictive performance for Class 2 (AUC=0.907, 95% CI 0.805-0.999), with Classes 0 and 1 following (AUC/accuracy=0.829/0.803 and 0.794/0.768, respectively). SHAP analysis provided a visualization of feature importance in the RadImageNet-based fused model, highlighting the top 3 most influential features: cluster shade, mean, and large area low gray level emphasis, and their respective impacts on predictions. CONCLUSIONS: The RadImageNet-based fused model using CT imaging data exhibited superior predictive performance compared to the ImageNet-based model, demonstrating significant utility in OVF classification and aiding clinical decision-making for treatment planning. Among the 3 classes, the model performed best in identifying Class 2, followed by Class 0 and Class 1.