Hormone refractory prostate cancer is dominated by osseous metastases. Bisphosphonates are able to reduce bone resorption. Sixteen hormone refractory prostate cancer patients with related bone metastases were included in the study. Group A consisted of patients who were not treated with bisphosphonates (n=9) and group B consisted of patients who had received bisphosphonates treatment previously, but not receiving currently (n=7). All patients were treated with the same analgesic medications. Clodronate 400 mg; 1200 mg/day (p.o.) was added to the treatment of the patients in group A. Visual Analogue Scale (VAS) scores, consumptions and side effects of analgesics were recorded by two week intervals. Alkaline phosphatase, creatinine and serum Ca++ levels were controlled by 4 week intervals. At the end of the 12th week, the study was ended. In Group A, VAS decreased at the end of the 2nd week but in Group B VAS decreased in the 4th week. VAS decreased 75% in group A and 65.7% in group B and the difference was considered statistically significant (p<0.0001). Clodronate treatment was stopped in 2 patients because of nausea, 7 patients are still being treated with clodronate. We conclude that bisphosphonates treatment of painful osseous metastasis due to hormone refractory prostate cancer results in significant pain decrease.