Serial markers of bone turnover in men with metastatic prostate cancer treated with zoledronic Acid for detection of bone metastases progression

Eur Urol. 2007 Nov;52(5):1381-7. doi: 10.1016/j.eururo.2007.02.033. Epub 2007 Feb 20.


Objectives: This study assessed the usefulness of serial measurements of bone turnover markers in men with metastatic prostate cancer treated with zoledronic acid to detect disease progression.

Methods: Serum measurements of total alkaline phosphatase (tALP), bone-specific alkaline phosphatase (bALP), cross-linked N-terminal (NTx) and cross-linked C-terminal (CTx) telopeptides of type I collagen, amino-terminal procollagen propeptides of type I collagen (PINP), C-terminal telopeptides of type I collagen (ICTP), and prostate-specific antigen (PSA) were performed in 77 prostate cancer patients suffering from bone metastases and treated with zoledronic acid up to 15 mo. Fifty patients were with and 27 patients without objective evidence of metastatic bone progression during the administration of zoledronic acid.

Results: The baseline bone marker concentrations were not significantly different between the groups. After administration of zoledronic acid all bone markers except of ICTP decreased compared with baseline. CTx showed the greatest decrease. In patients with metastatic bone progression PINP, tALP, bALP, and ICTP were significantly higher at weeks 24, 36, 48, and 60 after starting treatment with zoledronic acid compared with patients without progression. In addition to the information of prostate-specific antigen as a monitoring parameter, the bone formation marker showed a better distinction between patients with and without disease progression.

Conclusions: Selected bone turnover markers provide valuable information regarding progression of bone metastasis in men with metastatic prostate cancer under bisphosphonate therapy. The clinical impact should be confirmed in prospective randomised studies.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alkaline Phosphatase / blood
  • Biomarkers, Tumor / blood*
  • Bone Density Conservation Agents / administration & dosage
  • Bone Density Conservation Agents / therapeutic use*
  • Bone Neoplasms / blood*
  • Bone Neoplasms / drug therapy
  • Bone Neoplasms / secondary
  • Collagen Type I / blood
  • Diphosphonates / administration & dosage
  • Diphosphonates / therapeutic use*
  • Disease Progression
  • Dose-Response Relationship, Drug
  • Enzyme-Linked Immunosorbent Assay
  • Follow-Up Studies
  • Humans
  • Imidazoles / administration & dosage
  • Imidazoles / therapeutic use*
  • Male
  • Middle Aged
  • Peptide Fragments / blood
  • Peptides / blood
  • Procollagen / blood
  • Prognosis
  • Prospective Studies
  • Prostate-Specific Antigen / blood
  • Prostatic Neoplasms / blood*
  • Prostatic Neoplasms / drug therapy
  • Prostatic Neoplasms / pathology
  • Zoledronic Acid


  • Biomarkers, Tumor
  • Bone Density Conservation Agents
  • Collagen Type I
  • Diphosphonates
  • Imidazoles
  • Peptide Fragments
  • Peptides
  • Procollagen
  • collagen type I trimeric cross-linked peptide
  • Zoledronic Acid
  • Alkaline Phosphatase
  • Prostate-Specific Antigen