Optimal bone health management strategies in patients with prostate cancer

Abstract

Bone health is affected in patients with prostate cancer, both by the disease and its treatment. Metastases to bone leads to pain, fractures, and spinal cord compression; bone loss due to androgen deprivation therapy (ADT) leads to osteoporosis and its complications. Both these scenarios are a major cause of morbidity and adversely affect the quality of life of these patients. Maintaining an optimum bone health throughout the natural course of prostate cancer is an important aspect in the management of this disease. An understanding of the complex interplay between osteoclasts, osteoblasts, receptor activator of nuclear factor κB (RANK), and various other tyrosine kinases involved in the pathophysiology of bone metastases is essential. Zoledronic acid (ZA), an intravenously administered bisphosphonate, and Denosumab, a subcutaneously administered inhibitor of nuclear factor B ligand (RANKL), have already been approved by Food and Drug Administration (FDA) for their use in treatment of bone metastases. This article discusses the pathophysiology of bone metastases and bone loss due to ADT in prostate cancer, role of biomarkers, newer modalities of imaging, World Health Organization (WHO)/FRAX nomogram in evaluation of these patients, utility of currently available drugs and evidence supporting their use, and newer therapeutic agents like alpha-emitting Radium-223, endothelin-A receptor antagonists (Atrasentan and Zibotentan) and the proto-oncogene tyrosine-protein kinase (SRC) inhibitor, Dasatinib.

Keywords: Bisphosphonates; bone metastasis; osteoclasts; prostate cancer; skeletal related events; zoledronic acid.

Figure 1

Schematic illustration of bone metabolism in prostate cancer