Diagnosis and treatment of prostate cancer-related bone disease

Tilman Todenhoefer, Georgios Gakis, David Schilling, Gerhard Feil, Christian Schwentner,Arnulf Stenzl

Bone disease is a major problem for patients suffering from advanced prostate cancer. It can result either from metastatic osseous lesions severely impairing patients’ quality of life and overall survival or from androgen deprivation therapy (ADT) and secondary osteopenia osteoporosis associated with an increased risk for skeletal-related events. Activation of osteoclasts is essential for both ADT-induced osteoporosis and metastatic bone disease. The individual risk of developing fractures during ADT can be evaluated by analysis of bone mineral density and fracture risk models. General measures can be recommended to all patients receiving ADT. Bisphosphonates, RANKL inhibitors and selective estrogen receptor modulators are effective tools to reduce bone loss during ADT. Besides imaging, serum and urine markers are gaining increasing importance in diagnosis and follow up of bone metastases. Bisphosphonates are the current standard of bone-targeted treatment for patients with bone metastases. The RANKL inhibitor denosumab has recently been approved for the prevention of skeletal-related events in patients with metastatic bone disease from prostate cancer. Whether bisphosphonates and denosumab can prevent the development of bone metastases is being investigated at present. Endothelin-A receptor antagonists and Src-inhibitors are under investigation for treatment and prevention of bone metastases yielding different effectiveness in initial preliminary clinical trials