A dual experimental and numerical top-down approach is applied to investigate the link between osteocyte morphology and mechanical perception of their environment at the progenitor and mature stages. The numerical model is based on explicit tissue morphology discretization to identify bone diffuse damage at the cellular scale. The in vitro experimental model presents a live allograft bone system where a patient progenitor or mature osteocytes were reseeded in fresh human donor cortical bone tissues subjected to mechanical loading. The live systems behaved mechanically as fresh bone and the cells spatially reorganized in vitro as in vivo. The system under mechanical load also showed an adaptation of the calcium membrane transport rate to the expected in vivo mechanical load detected by bone cells at different stages of differentiation.