To identify regions inside the hip experiencing the most significant bone loss due to long-duration spaceflight, we have employed inter-subject registration to integrate hip quantitative computed tomography (QCT) scans and constructed the pre- and post-flight composite hip models for 16 astronauts, who experienced 4-6 months of spaceflights on the International Space Station. To achieve this, we applied automatic volumetric rigid and non-rigid inter-subject registration techniques to transform the two groups of hip QCT scans into a common reference hip space. Statistical comparison of the preand post-flight composite models illustrated tissue regions that showed the most serious bone loss inside the proximal femur. Based on the 16 subjects, such regions also showed statistical significance in bone loss according to voxel-by-voxel t-test and false discovery rate (FDR) analysis. By emphasizing on such most responsive regions, we can potentially develop more sensitive bone measurement methods for detecting and analyzing bone response to environmental and other factors, such as aging and osteoporosis drug therapies