109 patients with nonmetastatic prostate cancer, undergoing androgen deprivation therapy (ADT) in combination with radiotherapy (RT), were randomized to receive a 4-mg infusion of zoledronic acid every 6 months for 3 years, as well as vitamin D and calcium supplements, or supplements alone. The purpose of this study was to examine the safety and efficacy of zoledronic acid with respect to the incidence of bone fractures, quality of life, and bone mineral density (BMD). Results indicated that the administration of zoledronic acid as an adjuvant therapy to ADT and RT was well-tolerated and resulted in significantly better improvements in BMD for the lumbar spine, the left total hip and the left femoral neck at the 3-year follow-up. Although better improvements were also observed in the zoledronic acid group for right hip and right femoral neck, these differences were not statistically significant. There was no significant difference between groups in bone fractures or quality of life; however, at the 3-year follow-up, the study was not sufficiently powered to detect a difference for these outcomes.