Artificial Intelligence-Assisted Structural Analysis of Bones with Paget’s Disease of Bone and Osteoporosis: Lessons from Mouse Models

Background/Objectives: Paget’s disease of bone (PDB) and osteoporosis are chronic metabolic bone disorders characterized by disrupted bone remodeling and increased skeletal fragility; however, the underlying mechanism of PDB remains poorly understood. Artificial intelligence (AI) has emerged as a transformative tool in medical imaging, enabling automated feature extraction and improved diagnostic classification of skeletal disorders. This study aimed to investigate whether AI could distinguish subtle variations in bone morphology between PDB and osteoporotic bone. Methods: C57BL/6 mice femurs were scanned by µCT: 16 optineurin-knockout mice with a PDB phenotype (20–26 months), 25 genetically matched wild-type Aging mice (20–26 months), and 15 ovariectomized (OVX) mice with osteoporotic bone phenotype (4.5 months). Two AI algorithms were investigated: a machine learning (ML) model using 22 µCT-derived features trained with a Random Forest (RF) classifier, and a deep learning (DL) model using a 3D convolutional neural network (3D-CNN) trained on raw µCT images. Leave-one-out cross-validation was applied to evaluate model robustness. Results: Significant differences in volumetric, density, and morphological parameters of cortical and trabecular bone were observed between PDB and osteoporosis (p < 0.05). The RF algorithm achieved 90% accuracy in distinguishing PDB from both aging- and OVX-induced osteoporosis and provided feature importance rankings that improved model interpretability. The 3D-CNN achieved classification accuracies of 70% for PDB vs. OVX and 68% for PDB vs. aging, demonstrating the feasibility of an image-based DL approach. Conclusions: AI-based RF and 3D-CNN models demonstrated promising performance in differentiating PDB from osteoporosis using µCT-derived bone features. These findings suggest potential for using AI to assist with analyzing skeletal images in the diagnosis of metabolic bone disorders.