Bone health and prostate cancer

Abstract

Bone metastases are a substantial burden to men with advanced prostate cancer as they often cause pain and can cause fractures and spinal cord compression. Osteoblasts and osteoclasts are both pathologically activated in the setting of prostate cancer bone metastases. As osteoclast activation is associated with disease progression, skeletal complications and death, osteoclast-targeted therapies are a rational approach to disease management. Zoledronic acid is standard of care for castration-resistant prostate cancer with bone metastases as it reduces the risk for skeletal-related events. Additional trials are needed to better define the ideal dose, frequency and duration of zoledronic acid therapy. No bisphosphonate has yet been shown to prevent bone metastases or to benefit men with androgen-sensitive disease. Denosumab is an experimental osteoclast-targeted monoclonal antibody against receptor activator of nuclear factor-kappaB ligand. Two ongoing phase III trials are expected to define its efficacy in preventing bone metastases and disease-related skeletal events in men with prostate cancer. Androgen-deprivation therapy (ADT) for prostate cancer is associated with osteoporosis and fragility fractures. Several bisphosphonates have been shown to improve bone mineral density in men receiving ADT. Two recent phase III trials have shown that denosumab and toremifene reduce the incidence of fragility fractures in these men. The World Health Organization has developed a fracture risk assessment model (FRAX) for the general population to guide the selection of patients who may benefit from pharmacotherapy. In the absence of a prostate cancer-specific algorithm, we advocate the use of FRAX for men receiving ADT.

Figure 1

Cumulative incidence of skeletal-related events. In combined analysis of two large prospective randomized controlled trials, the survival-adjusted cumulative incidence of skeletal-related events was significantly reduced by 35.3% relative to placebo with the use of 4mg zoledronic acid.,