Serum osteoprotegerin and receptor activator of nuclear factor-kappa B ligand as indicators of disturbed osteoclastogenesis in patients with prostate cancer

J Urol. 2003 Dec;170(6 Pt 1):2302-5. doi: 10.1097/01.ju.0000094191.39574.cb.


Purpose: We evaluated the behavior and diagnostic usefulness of the osteoclastogenesis proteins osteoprotegerin and receptor activator of nuclear factor-kappaB ligand (RANKL) in the serum of patients with prostate cancer (PCa).

Materials and methods: Serum osteoprotegerin and RANKL were retrospectively measured in 117 patients with prostate cancer, including 39 with stage pN0M0, 34 with stage pN1M0 and 44 with bone metastases, in 35 presumably healthy men and in 35 patients with benign prostatic hyperplasia (BPH). The association of these components with clinical data (tumor stage and grade) and receiver operating characteristics curves compared with the bone formation marker alkaline phosphatase and bone resorption marker crosslaps (cross-linked C-terminal telopeptides of type I collagen) were calculated.

Results: Osteoprotegerin was increased in patients with bone metastases, while those with localized cancer or lymph node metastases had values similar to those in presumably healthy controls and patients with BPH. RANKL did not differ among the control, BPH and PCa subgroups. Thus, the ratio of osteoprotegerin-to-RANKL showed behavior similar to that of osteoprotegerin. Osteoprotegerin and RANKL did not show any significant correlation with tumor stage, histological tumor grade, total prostate specific antigen, alkaline phosphatase activity or crosslaps. ROC analysis data proved that osteoprotegerin had a better diagnostic accuracy than alkaline phosphatase or crosslaps for detecting bone metastases in PCa cases.

Conclusions: Serum osteoprotegerin but not RANKL indicates disturbed osteoclastogenesis in patients with PCa and bone metastatic spread. It could be used as a marker for bone metastases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Alkaline Phosphatase / blood
  • Biomarkers, Tumor / blood
  • Bone Neoplasms / blood
  • Bone Neoplasms / diagnosis
  • Bone Neoplasms / secondary*
  • Carcinoma / blood*
  • Carcinoma / physiopathology
  • Carcinoma / secondary
  • Carrier Proteins / blood*
  • Collagen / blood
  • Collagen Type I
  • Glycoproteins / blood*
  • Humans
  • Lymphatic Metastasis
  • Male
  • Membrane Glycoproteins / blood*
  • Middle Aged
  • Osteogenesis*
  • Osteoprotegerin
  • Peptides / blood
  • Prostatic Hyperplasia / blood
  • Prostatic Neoplasms / blood*
  • Prostatic Neoplasms / pathology
  • Prostatic Neoplasms / physiopathology
  • RANK Ligand
  • ROC Curve
  • Receptor Activator of Nuclear Factor-kappa B
  • Receptors, Cytoplasmic and Nuclear / blood*
  • Receptors, Tumor Necrosis Factor / blood
  • Retrospective Studies
  • Sensitivity and Specificity


  • Biomarkers, Tumor
  • Carrier Proteins
  • Collagen Type I
  • Glycoproteins
  • Membrane Glycoproteins
  • Osteoprotegerin
  • Peptides
  • RANK Ligand
  • Receptor Activator of Nuclear Factor-kappa B
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Tumor Necrosis Factor
  • TNFRSF11A protein, human
  • TNFRSF11B protein, human
  • TNFSF11 protein, human
  • collagen type I trimeric cross-linked peptide
  • Collagen
  • Alkaline Phosphatase