Serial markers of bone turnover in men with metastatic prostate cancer treated with zoledronic Acid for detection of bone metastases progression.
OBJECTIVE
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.
Lein
Michael
M
Department of Urology, Charité Hospital Berlin Mitte, University Medicine Berlin, Berilin, Germany. michael.lein@charite.de
Wirth
Manfred
M
Miller
Kurt
K
Eickenberg
Hans-Udo
HU
Weissbach
Lothar
L
Schmidt
Katja
K
Haus
Ulrike
U
Stephan
Carsten
C
Meissner
Sven
S
Loening
Stefan A
SA
Jung
Klaus
K
D000368:Aged; D000469:Alkaline Phosphatase / Q000097:blood; D014408:Biomarkers, Tumor / Q000097:blood*; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000556:secondary; D024042:Collagen Type I / Q000097:blood; D004164:Diphosphonates / Q000008:administration & dosage / Q000627:therapeutic use*; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005500:Follow-Up Studies; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood; D010455:Peptides / Q000097:blood; D011347:Procollagen / Q000097:blood; D011379:Prognosis; D011446:Prospective Studies; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000473:pathology; D000077211:Zoledronic Acid
D014408:Biomarkers, Tumor; D050071:Bone Density Conservation Agents; D024042:Collagen Type I; D004164:Diphosphonates; D007093:Imidazoles; D010446:Peptide Fragments; D010455:Peptides; D011347:Procollagen; C052929:collagen type I trimeric cross-linked peptide; D000077211:Zoledronic Acid; D000469:Alkaline Phosphatase; D017430:Prostate-Specific Antigen