Different corticotomy surgical procedures have been developed to shorten orthodontic treatment times by stimulating bone remodeling. Although all corticotomy procedures involve physical injury to the bone, the clinical outcomes can vary. Using an ex vivo calvarial bone organ culture model system, the authors evaluated the biologic response of bone to different corticotomies. Bone injuries were generated in 276 calvaria dissected from 5- to 7-day-old neonatal mice using a piezoelectric knife, a bur, and a handheld screw device. The responses were evaluated using chemical, biochemical, and global histomorphometric analyses. Injuries generated by the three approaches induced varying degrees of bone remodeling activities; however, the piezoelectric knife led to the most extensive impact in both bone resorption and formation models.