Integration of Multi-Scale Predictive Tools of Bone Fragility: A Structural and Material Property Perspective

Bone fragility represents a significant global health burden, characterized by the deterioration of bone strength, increased brittleness, and heightened fracture susceptibility. Osteoporosis substantially elevates the risk of fragility fractures, the principal clinical manifestation of the disease. Current diagnostic approaches, including biomedical imaging, bone strength assessment, and bone mineral density measurement, are closely linked to identifying bone fragility through various predictive models and tools. Although numerous studies have employed predictors to characterize fragility fractures, few have comprehensively examined the morpho-structural features of bone across multiple hierarchical scales, limiting the ability to fully elucidate the underlying mechanisms of bone fragility. This review summarizes recent advancements in predictive modeling and novel diagnostic tools, focusing on multiscale approaches for assessing bone fragility. We critically evaluate the translational potential of these tools for the early detection of fragility fractures and their clinical application in mitigating fracture risk. Moreover, this study discusses the integration of multiscale predictive methodologies, which promise to enhance early-stage bone fragility detection and potentially prevent severe fractures through timely intervention. Finally, the study reflects on current research limitations, addressing the challenges associated with multiscale predictive modeling of bone fragility, and proposes future directions to refine these tools to improve the accuracy and utility of fragility fracture prediction and prevention strategies.