Frontiers in Aging Neuroscience · May 20, 2026
Cognitive decline and reduced bone mineral density under the bone-brain axis: mechanistic insights and imaging evaluation strategies
By Mao Y, Sui Z, Zhang M et al.
Against the backdrop of an accelerating global aging population, the epidemiological correlation between cognitive impairment and osteoporosis has become increasingly prominent. These two conditions exhibit a profound pathological coupling mediated by the bidirectional regulatory network of the "bone-brain axis." The operation of this axis is rooted in an intricate neuro-skeletal signaling network involving hormonal dysregulation, systemic inflammatory cascades, and the aberrant regulation of core molecular pathways, such as Wnt/β-catenin and RANKL/OPG. Together, these factors synergistically drive the synchronized pathological progression of enhanced bone resorption and neurodegeneration. To address these complex pathological interactions, clinical evaluation strategies are undergoing a paradigm shift, transitioning from single-modality assessments toward the deep integration of multimodal imaging. By fusing cutting-edge technologies-including structural/functional MRI, molecular PET imaging (targeting Aβ and Tau deposition), and high-resolution peripheral quantitative computed tomography (HR-pQCT)-researchers can now comprehensively characterize the spatiotemporal patterns of bone microstructural degradation and brain functional evolution across scales ranging from the microscopic to the macroscopic. Prospectively, leveraging deep learning algorithms such as 3D-CNN to integrate multimodal biomarkers and construct risk-prediction models for bone-brain comorbidities will emerge as a pivotal pathway for achieving early precision screening and personalized preventive intervention for Alzheimer's disease (AD).