Denosumab treatment of prostate cancer with bone metastases and increased urine N-telopeptide levels after therapy with intravenous bisphosphonates: results of a randomized phase II trial

J Urol. 2013 Jan;189(1 Suppl):S51-7; discussion S57-8. doi: 10.1016/j.juro.2012.11.022.


Purpose: Patients with bone metastases have high rates of RANKL driven bone resorption and an increased risk of skeletal morbidity. Osteoclast mediated bone resorption can be assessed by measuring urine N-telopeptide and can be inhibited by denosumab, a fully human antibody against RANKL.

Materials and methods: Eligible patients (111) had bone metastases from prostate cancer, other solid tumors or multiple myeloma, 1 or more bone lesions and urine N-telopeptide greater than 50 nM bone collagen equivalents per mM creatinine (urine N-telopeptide greater than 50) despite the use of intravenous bisphosphonates. Patients were stratified by cancer type and screening urine N-telopeptide, and randomized to continue intravenous bisphosphonates every 4 weeks or receive 180 mg subcutaneous denosumab every 4 weeks or 180 mg every 12 weeks. The primary end point was the proportion of patients with urine N-telopeptide less than 50 at week 13. We report the efficacy results for the subset of patients with prostate cancer.

Results: Patients with prostate cancer represented 45% (50 of 111) of the study population. At week 13, 22 of 32 (69%) patients in the denosumab arms had urine N-telopeptide less than 50 vs 3 of 16 (19%) in the intravenous bisphosphonates cohort. At week 25, 22 of 32 (69%) denosumab treated patients continued to have urine N-telopeptide less than 50 vs 5 of 16 (31%) treated with intravenous bisphosphonates. Grade 4, asymptomatic, reversible hypophosphatemia, possibly related to denosumab, was reported in 1 patient.

Conclusions: In patients with prostate cancer related bone metastases and increased urine N-telopeptide despite intravenous bisphosphonate treatment, denosumab normalized urine N-telopeptide levels more frequently than ongoing intravenous bisphosphonates.

Trial registration: NCT00104650.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Bone Density Conservation Agents / administration & dosage
  • Bone Density Conservation Agents / therapeutic use*
  • Bone Neoplasms / drug therapy*
  • Bone Neoplasms / secondary
  • Bone Neoplasms / urine*
  • Collagen Type I / urine*
  • Denosumab
  • Diphosphonates / administration & dosage
  • Diphosphonates / therapeutic use*
  • Humans
  • Injections, Intravenous
  • Male
  • Middle Aged
  • Peptides / urine*
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / pathology
  • Prostatic Neoplasms / urine*


  • Antibodies, Monoclonal, Humanized
  • Bone Density Conservation Agents
  • Collagen Type I
  • Diphosphonates
  • Peptides
  • collagen type I trimeric cross-linked peptide
  • Denosumab

Associated data