Cancer Treatment-Induced Bone Loss (CTIBL) in Prostate Cancer: Pathophysiology, Preclinical Findings, and Treatment with Zoledronic Acid

Abstract

Objective: Androgen deprivation therapy (ADT) is the treatment of choice for men with advanced prostate cancer, and the most common indication for the initiation of ADT is a rising serum prostate-specific antigen level after failed local therapy. Consequently, potentially long periods of androgen suppression exist in these patients, resulting in clinically significant bone loss. This review will discuss the pathophysiology of cancer treatment-induced bone loss (CTIBL) and the treatment and prevention of CTIBL with zoledronic acid. Methods: Relevant information was identified through searches of published studies, abstracts from scientific meetings, and review articles. Results: The treatment of prostate cancer patients with surgical or pharmacologic ADT results in the activation of osteoclast-mediated bone resorption, leading to reductions in bone mineral density (BMD) and increased fracture risk. Preclinical evidence from a murine prostate cancer model also suggests that ADT may potentially increase the risk of bone metastasis. Bone loss caused by long-term ADT and bone metastases can result in significant skeletal morbidity in patients with prostate cancer. Zoledronic acid has been shown to increase BMD in prostate cancer patients receiving ADT, and is the only bisphosphonate effective in reducing the risk of skeletal complications in prostate cancer patients with bone metastases in the setting of hormone-refractory disease. In addition, preclinical evidence suggests that zoledronic acid may prevent tumor metastasis to bone. Conclusions: Zoledronic acid can provide clinical benefit for patients with advanced prostate cancer throughout the course of their disease. In these patients BMD should be monitored routinely, and zoledronic acid treatment should be considered to prevent bone loss.