title: Bone turnover markers as predictors of mortality risk in prostate cancer patients with bone metastases following treatment with zoledronic acid.
abstract: BACKGROUND
  Clinical data have limited validity for predicting the survival of prostate cancer (PCa) patients with bone metastases. There is a need to improve the predictive evidence both for clinicians and patients.
  
  
  OBJECTIVE
  To evaluate the predictive ability of serum bone markers for mortality risk in PCa patients with bone metastases.
  
  
  METHODS
  We conducted a survival analysis in relation to bone markers in a subgroup of 52 patients treated with zoledronic acid (4 mg every 4 wk for 15 mo) in a prospective, multicentre trial during 2002-2005, about 4 yr after the end of the trial.
  
  
  METHODS
  Serum levels of total and bone-specific alkaline phosphatase, amino-terminal procollagen propeptides of type I collagen (PINP), cross-linked N-terminal (NTx) and cross-linked C-terminal telopeptides of type I collagen (ICTP), C-terminal telopeptides of type I collagen, prostate-specific antigen from the last visit of the treatment study, and clinical data were related to the overall survival (OS) status of patients in the follow-up. Univariate and multivariate Cox regression analyses with internal bootstrapping validation and concordance index calculations were performed.
  
  
  CONCLUSIONS
  Out of the 52 patients followed, 34 died within a median follow-up of 13.8 mo, and 18 patients were alive at a median follow-up of 43.8 mo. The patients who died within the follow-up period had significantly higher concentrations of ICTP, NTx, and PINP than the surviving patients. Cox regression models with clinical data and bone markers showed that ICTP and PINP were most predictive for mortality risk in addition to the occurrence of skeletal-related complications and the continuation of treatment with zoledronic acid. Internal validation confirmed the reliability of the results, although the sample size was small.
  
  
  CONCLUSIONS
  PINP and ICTP can be considered suitable predictors for the OS of PCa patients with bone metastases.
authors.affiliation: Department of Urology, University Hospital Charité, Berlin, Germany. klaus.jung@charite.de
authors.forename: Klaus
authors.initials: K
authors.lastname: Jung
authors.forename: Kurt
authors.initials: K
authors.lastname: Miller
authors.forename: Manfred
authors.initials: M
authors.lastname: Wirth
authors.forename: Michael
authors.initials: M
authors.lastname: Albrecht
authors.forename: Michael
authors.initials: M
authors.lastname: Lein
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood*; D050071:Bone Density Conservation Agents / Q000008:administration & dosage; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000401:mortality* / Q000556:secondary; D016723:Bone Remodeling / Q000187:drug effects / Q000502:physiology*; D002986:Clinical Trials as Topic; D024042:Collagen Type I / Q000097:blood; D004164:Diphosphonates / Q000008:administration & dosage*; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage*; D053208:Kaplan-Meier Estimate; D008297:Male; D015337:Multicenter Studies as Topic; D010446:Peptide Fragments / Q000097:blood; D010455:Peptides / Q000097:blood; D011237:Predictive Value of Tests; D011347:Procollagen / Q000097:blood; D016016:Proportional Hazards Models; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000401:mortality* / Q000473:pathology; D012307:Risk Factors; D011795:Surveys and Questionnaires; D000077211:Zoledronic Acid
chemical_list: 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; C047202:procollagen Type I N-terminal peptide; D000077211:Zoledronic Acid; D017430:Prostate-Specific Antigen