UroToday - Prostate cancer (CaP) has a predilection to metastasize to bone, resulting in skeletal-related events (SREs). The cancer cells interact with osteoclasts (bone resorption), and osteoblasts (bone formation) to create a vicious cycle of tumor growth and bone destruction.

The receptor activator of NF-kB ligand (RANKL) is secreted by osteoblasts in response to tumor cells and is an essential mediator of osteoclast formation, function and survival. Binding of RANKL to its receptor RANK on osteoclasts promotes increased osteoclast formation and bone resorption. Inhibition of RANKL has been shown as beneficial in animal models of bone metastasis.

In the July issue of the Journal of Urology, Dr. Karim Fizazi and colleagues report results of a Phase II trial using denosumab, a monoclonal antibody against RANKL in patients with bone metastasis. The study was a multicenter, phase II, randomized open label, active controlled study conducted at 26 centers in Europe and North America from 2004 to 2008. It compared 2 different doses of subcutaneous denosumab and IV bisphosphonates. Participants had bone metastasis from CaP, other solid tumors except lung cancer, or multiple myeloma.

Urine N-telopeptide (uNTx), a marker of bone turnover is known to correlate with clinical prognosis and was measured. uNTx >50nM BCE/MM creatinine represents excess bone resorption and is associated with increased risk of SREs, cancer progression and death. Denosumab was delivered as 180mg sc every 4 weeks or every 12 weeks and IV bisphosphonates (BP) given every 4 weeks. The primary endpoint was the proportion of patients with uNTx