Cortical bone porosity is spatially heterogeneous and VEGF dependent in male bone.

Cortical bone is highly porous and composed of an interconnecting network of vascular canals and osteocyte lacunae. Our understanding of the mechanisms coupling vascular: lacunar spatial organisation in cortical bone is poorly understood. Defining cellular cross-talk mechanisms could be key in identification of reciprocal molecular signals driving increased cortical porosity with age. Driven by the hypothesis that porosity within bone is heterogeneous and influenced by region-specific spatial cues, we utilised synchrotron X-ray computed tomography to characterise intracortical canal and osteocyte lacunae distribution, morphology and spatial arrangements in healthy and pathological murine bone. We found that the posterior region of the tibiofibular junction (TFJ) exhibited the highest levels of cortical porosity and highest canal number density compared to other regions. The volume of osteocyte lacunae positioned proximal to cortical vascular canals was highest in the posterior region. Following deletion of bone-derived VEGF, the region-specific effects on lacunar: vascular arrangements described in the wild-type TFJ were lost. Our results describe spatial diversity in osteocyte lacunae size within the bone cortex, which associates with vascular canal arrangements maintained by VEGF.