Spinal cord injury (SCI) leads generally to significant bone tissue loss within a few months to a few years post-trauma. Although, increasing data from rat models are available to study the underlying mechanisms of SCI-associated bone loss, little is known about the extent and rapidity of bone tissue changes in mouse models of SCI. The objectives are to characterize and describe quantitatively femoral bone tissue changes during 1 month in adult paraplegic mice. Histomorphometric and densitometric measurements were performed in 3- to 4-month-old CD1 mice spinal cord transected at the low-thoracic level (Th9/10). We found a general decrease in bone volume (-22%), trabecular thickness (-10%), and trabecular number (-14%) within 30 days post-transection. Dual-energy X-ray absorptiometric measurements revealed no change in bone mineral density but a significant reduction (-14%) in bone mineral content. These results show large structural changes occurring within only a few weeks post-spinal cord transection in the femora of adult mice. Given the increasing availability of genetic and molecular research tools for research in mice, this murine model may be useful to study further the cellular and molecular mechanisms of demineralization associated with SCI.