Bone turnover markers as predictive tools for skeletal complications in men with metastatic prostate cancer treated with zoledronic acid.
BACKGROUND
Bone turnover markers are helpful to diagnose bone metastases. The aim of this study was to evaluate the usefulness of these markers in prostate cancer patients with bone metastases before and during the treatment with zoledronic acid as predictive and monitoring tools of skeletal-related events (SRE).


METHODS
One hundred seventeen prostate cancer patients with bone metastases and treated with zoledronic acid (4 mg every 4 weeks) were examined. Fifty-six patients were with and 61 patients without SRE during a 60-week study. Total and bone-specific alkaline phosphatase, and amino-terminal procollagen propeptides of type-I-collagen (PINP), cross-linked N-terminal (NTx), cross-linked C-terminal telopeptides of type-I-collagen (ICTP), and C-terminal telopeptides of type-I-collagen as well as prostate-specific antigen (PSA) were measured before and 12, 24, 36, 48, and 60 weeks after starting treatment.


RESULTS
Higher baseline concentrations were observed in the SRE group. The bone markers except for ICTP and tALP decreased to 20-80% of the baseline values at week 12 after the drug administration showing a generally higher decline in the non-SRE group except for NTx. At all time points during treatment higher and increasing concentrations of bone markers were observed in the SRE group compared with non-SRE group. Cox regression models with clinical data and bone markers showed the baseline NTx concentration as predictor of SREs. During the study, percentage changes of PINP and ICTP were most indicative for SREs.


CONCLUSIONS
Bone markers are useful tools to predict and diagnose SRE in prostate cancer patients with bone metastases under receiving zoledronic acid therapy.
Lein
Michael
M
Department of Urology, Charité Hospital Berlin, University Medicine Berlin, Berlin, Germany.
Miller
Kurt
K
Wirth
Manfred
M
Weissbach
Lothar
L
May
Christoph
C
Schmidt
Katja
K
Haus
Ulrike
U
Schrader
Mark
M
Jung
Klaus
K
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000970:Antineoplastic Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000378:metabolism; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D001847:Bone Diseases / Q000188:drug therapy* / Q000209:etiology* / Q000517:prevention & control; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism*; D024042:Collagen Type I; D004164:Diphosphonates / Q000627:therapeutic use*; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use*; D008297:Male; D015999:Multivariate Analysis; D010446:Peptide Fragments / Q000187:drug effects / Q000378:metabolism; D010455:Peptides; D011237:Predictive Value of Tests; D011347:Procollagen / Q000187:drug effects / Q000378:metabolism; D017430:Prostate-Specific Antigen / Q000187:drug effects / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000150:complications* / Q000188:drug therapy / Q000473:pathology*; D012044:Regression Analysis; D000077211:Zoledronic Acid
D000970:Antineoplastic Agents; D015415:Biomarkers; 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; D017430:Prostate-Specific Antigen