BONE
METASTASES OFTEN CREATE SERIOUS CLINICAL PROBLEMS: they lead to poor performance status due to
pathologic fractures,
spinal cord compression and
intractable pain, commonly referred to as skeletal-related events. The receptor activator of nuclear factor-κB (RANK), the
RANK ligand (RANKL), and
osteoprotegerin, a decoy receptor for RANK, regulate osteoclastogenesis and may play a key role in bone
metastasis.
Denosumab (
XGEVA; Amgen, Thousand Oaks, CA), a fully human
monoclonal antibody that binds to and neutralizes RANKL, inhibits osteoclast function, prevents generalized
bone resorption and local bone destruction, and has become a therapeutic option for preventing or delaying first on-study skeletal-related events in various
malignancies. In the context of
urological cancer, three main Phase III clinical studies have been published in
prostate cancer. This article provides a brief overview of the characteristics of bone
metastasis in
urological cancers, reviews the mechanisms of bone
metastasis, including the RANK/RANKL/
osteoprotegerin axis, the current standard of care,
zoledronic acid, and describes the efficacy of the novel bone-targeted agent
denosumab in bone
metastasis.
Denosumab is emerging as a key therapeutic option in the treatment of bone
metastases from
urological cancers.