Gonadic deficiency and corticotherapy are important risk factors in the pathogenesis of osteoporosis. This study was outlined to assess the effects of combined orchidectomy (ORX) and corticosteroid (cortisol; CS) administration on bone remodeling and metabolism. Twenty-week-old male Swiss mice were randomized into four groups: either sham operated (sham), ORX, CS injected (CS), or ORX and CS injected (ORX + CS). After 28 days, mice were euthanized. Both ORX and CS resulted in reduced trabecular volume, and mineral apposition rate and increased osteoclast number and activity. TRAcP levels were increased in ORX and CS mice, but reached highest values in ORX + CS. Bone and serum mineral content (calcium and phosphorus) were disrupted in ORX and CS groups when compared to Sham, and were more affected in ORX + CS group. Urinary calcium measures were increased in ORX, CS, and ORX + CS during the time course of the study. Increases were more prominent in ORX + CS. The differences between groups were generally more accentuated at ORX + CS group. Biochemical data showed a parallel extent to the histologic and histomorphometric changes. This study provides a valid pre-clinical model for severe and rapid osteopenia by ORX associated corticotherapy in which bone loss was significantly higher than either ORX or CS alones.