A multimodal 3D imaging approach of pore networks in the human femur to assess age-associated vascular expansion and Lacuno-Canalicular reduction.

Cellular communication in the mechanosensory osteocyte Lacuno-Canalicular Network (LCN) regulates bone tissue remodeling throughout life. Age-associated declines in LCN size and connectivity dysregulate mechanosensitivity to localized remodeling needs of aging or damaged tissue, compromising bone quality. Synchrotron radiation-based micro-Computed Tomography (SRμCT) and Confocal Laser Scanning Microscopy (CLSM) were employed to visualize LCN and vascular canal morphometry in an age series of the anterior femur (males n = 14, females n = 11, age range = 19-101, mean age = 55). Age-associated increases in vascular porosity were driven by pore coalescence, including a significant expansion in pore diameter and a significant decline in pore density. In contrast, the LCN showed significant age-associated reductions in lacunar volume fraction, mean diameter, and density, and in canalicular volume fraction and connectivity density. Lacunar density was significantly lower in females across the lifespan, exacerbating their age-associated decline. Canalicular connectivity density was also significantly lower in females but approached comparable declining male values in older age. Our data illuminate the trajectory and potential morphometric sources of age-associated bone loss. Increased vascular porosity contributes to bone fragility with aging, while an increasingly reduced and disconnected LCN undermines the mechanosensitivity required to repair and reinforce bone. Understanding why and how this degradation occurs is essential for improving the diagnosis and treatment of age-related changes in bone quality and fragility.