Advanced-stage
prostate cancer is associated with skeletal complications related to metastatic disease and its treatment. On the one hand, metastatic disease to bone is commonly associated with skeletal-related events (SREs); on the other hand, treatment with
androgen-deprivation
therapy (ADT) leads to loss in bone mineral density (BMD) and increased risk of fracture. Despite osteoblastic appearance on radiography, bone
metastases from
prostate cancer are associated with increased osteoblast and osteoclast activity providing the rationale for treatment with osteoclast-targeted agents. The
bisphosphonate zoledronic acid and the
monoclonal antibody denosumab reduce the incidence of SREs in metastatic
castration-resistant
prostate cancer (mCRPC). A number of agents prevent loss of BMD associated with ADT, but only
denosumab is approved to reduce fractures in patients with non-metastatic
prostate cancer. Another recently approved agent-radium-223-improves survival and delays SREs in mCRPC. The inhibitors of
androgen receptor signalling,
abiraterone and
enzalutamide, improve survival in mCRPC and delay SREs, although the latter is likely related to control of disease rather than a direct effect on bone. Finally, the
tyrosine kinase inhibitor cabozantinib shows promising activity in bone
metastases from mCRPC. This Review addresses the skeletal morbidity associated with
prostate cancer and the therapeutic options that exist to treat it.