OBJECTIVE: To investigate the effects of the atypical antipsychotics drugs (AADs), olanzapine and risperidone, on femoral bone characteristics in female C57BL/6J mice. METHODS: Mice were treated with placebo or AADs (olanzapine or risperidone) for 3-4 weeks. Femoral cortical and trabecular bone characteristics were determined using micro-computed tomography. RESULTS: Olanzapine-treated mice tended to have lower trabecular bone volume (P = 0.088) and connectivity (P = 0.057) but no significant differences in bone density (P = 0.521) relative to controls. Risperidone-treated mice had significantly lower trabecular bone density (P = 0.001) and volume (P = 0.008), bone volume/total volume (P = 0.001), connectivity (P = 0.007), and trabecular number (P = 0.003) relative to controls. Cortical bone was not significantly affected by olanzapine or risperidone treatment. CONCLUSION: AADs inhibited trabecular bone accrual in C57BL/6J mice suggesting that alternative treatment options may need to be considered for the schizophrenia patient with potential osteoporosis risk.