We previously showed that after femur fracture, mice lose bone at distant skeletal sites, including the lumbar vertebrae. This bone loss may increase the risk of subsequent vertebral fractures, particularly if bone is lost from high-strain bone regions, which are most commonly found adjacent to the superior and inferior endplates of the vertebral body. To determine regional bone loss from the lumbar spine following femur fracture, we evaluated the cranial, center, and caudal portions of the L5 vertebral bodies of Young (3 month-old) and Middle-Aged (12 month-old) female C57BL/6 mice two weeks after a transverse femur fractures compared to Young and Middle-Aged uninjured control mice. We hypothesized that greater bone loss would be observed in the cranial and caudal regions than in the center region in both Young and Middle-Aged mice. Trabecular and cortical bone microstructure were evaluated using micro-computed tomography, and osteoclast number and eroded surface were evaluated histologically. In Young Mice, fracture led to decreased trabecular and cortical bone microstructure primarily in the cranial and caudal regions, but not the center region, while Middle-Aged mice demonstrated decreases in trabecular bone in all regions, but did not exhibit any changes in cortical bone microstructure after fracture. No significant differences in osteoclast number or eroded surface were observed at this time point. These data suggest that bone loss following fracture in Young Mice is concentrated in areas that contain a large amount of high-strain tissue, whereas bone loss in Middle-Aged mice is less region-dependent and is restricted to the trabecular bone compartment. These results illustrate how systemic bone loss after fracture could lead to decreases in vertebral strength, and how distinct regional patterns and age-dependent differences in bone loss may differentially affect vertebral fracture risk.