Topology optimization is currently the only way to provide bone microstructure information by enhancing a 600 μm low-resolution image into a 50 μm high-resolution image. Particularly, the recently proposed localized reconstruction method for the region of interest has received much attention because it has a high possibility to overcome inefficiency such as iterative large-scale problems of the conventional reconstruction. Despite the great potential, the localized method should be thoroughly validated for clinical application. This study aims to quantitatively validate the topology optimization-based localized bone microstructure reconstruction method in terms of accuracy and efficiency by comparing the conventional method. For this purpose, this study re-constructed bone microstructure for three regions of interest in the proximal femur by localized and conventional methods, respectively. In the comparison, the dramatically reduced total progress time by at least 88.2% (20.1 h) as well as computational resources by more than 95.9% (54.0 gigabytes) were found. Moreover, very high reconstruction accuracy in the trabecular alignment (up to 99.6%) and morphometric indices (up to 2.71%) was also found. These results indicated that the localized method could reconstruct bone microstructure, much more effectively preserving the originality of the conventional method.