In situ nanoscopic observations of healthy and osteoporotic bone nanopillars under compression were performed. The structural-mechanical property relationship at the atomic scale suggests that cortical bone performance is correlated to the feature, arrangement, movement, distortion, and fracture of hydroxyapatite nanocrystals. Healthy bone comprising tightly bound mineral nanocrystals shows high structural stability with nanoscopic lattice distortions and dislocation activities. On the other hand, osteoporotic bone exhibits brittleness owing to the movements of dispersed minerals in and intergranular fracture along a weak organic matrix.