Bone metastases, together with generalized bone resorption, represent the main complication in patients with advanced prostate cancer, and palliative treatments are required to delay the progression of the metastases and improve the quality of life of these patients. For this reason, the bisphosphonate clodronate was administered to 18 patients (clodronate group) from a total of 30, all of whom were receiving complete androgenic blockade; the remaining 12 formed the control group. Transiliac bone biopsies were taken at the beginning of the study and 6 months later to determine the effect of the bisphosphonate on the skeleton. The results were assessed by bone histomorphometry and showed, although without statistical significance between the groups, an antiresorptive effect of the clodronate expressed as the eroded surface/bone surface and as the osteoclast number/bone surface. However, the bone volume also decreased after 6 months of treatment. Similarly, osteoid formation decreased as indicated by the osteoid surface and by the osteoid volume, probably due to the effect of the drug on the osteoblasts. The mineralization rate was apparently slightly retarded in the clodronate group, although to a lesser degree than in the control group. The results confirm the antiresorptive effect of clodronate and its detrimental effect on osteoblast activity.