title: Markers of bone metabolism and survival in men with hormone-refractory metastatic prostate cancer.
abstract: OBJECTIVE
  To evaluate the relative prognostic value for specific markers of osteoblast and osteoclast activity while controlling for previously reported prognostic variables among men with hormone-refractory metastatic prostate cancer.
  
  
  METHODS
  The 643 subjects in this report were participants in multicenter randomized controlled trial of zoledronic acid in men with metastatic prostate cancer. All subjects had bone metastases and disease progression despite medical or surgical castration. Relationships between baseline covariates and overall survival were examined by Cox proportional hazard model. Serum bone-specific alkaline phosphatase (BAP) and urinary N-telopeptide were assessed as representative specific markers of osteoblast and osteoclast activity, respectively. Other covariates in the model were age, log prostate-specific antigen, hemoglobin, lactate dehydrogenase, albumin, analgesic use, and Eastern Cooperative Oncology Group performance status.
  
  
  RESULTS
  Serum BAP was significantly correlated with urinary N-telopeptide (correlation coefficient = 0.674; 95% confidence interval, 0.628-0.715; P < 0.0001). In univariate analyses, higher levels of serum BAP and urinary N-telopeptide levels were significantly associated with shorter overall survival. After controlling for the other variables, including N-telopeptide, in multivariate models, higher serum BAP levels were consistently associated with shorter survival. In contrast, urinary N-telopeptide levels were not significantly associated with survival in multivariate analyses. Variables retained in the reduced multivariate model were age, log prostate-specific antigen, hemoglobin, lactate dehydrogenase, analgesic use, and BAP.
  
  
  CONCLUSIONS
  Serum BAP significantly correlates with urinary N-telopeptide in men with androgen-independent prostate cancer and bone metastases. In multivariate models, higher levels of serum BAP but not urinary N-telopeptide are associated with shorter overall survival.
authors.affiliation: Department of Statistics and Actuarial Science, University of Waterloo, Waterloo, Ontario, Canada.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Cook
authors.forename: Robert
authors.initials: R
authors.lastname: Coleman
authors.forename: Janet
authors.initials: J
authors.lastname: Brown
authors.forename: Allan
authors.initials: A
authors.lastname: Lipton
authors.forename: Pierre
authors.initials: P
authors.lastname: Major
authors.forename: Yong Jiang
authors.initials: YJ
authors.lastname: Hei
authors.forename: Fred
authors.initials: F
authors.lastname: Saad
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Smith
mesh_terms: D000368:Aged; D000469:Alkaline Phosphatase / Q000097:blood*; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000097:blood* / Q000652:urine; D001859:Bone Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000556:secondary*; D004164:Diphosphonates / Q000627:therapeutic use; D018450:Disease Progression; D005500:Follow-Up Studies; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use; D008297:Male; D015337:Multicenter Studies as Topic / Q000706:statistics & numerical data; D015999:Multivariate Analysis; D010455:Peptides / Q000652:urine; D011379:Prognosis; D016016:Proportional Hazards Models; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism*; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data; D015996:Survival Rate; D016896:Treatment Outcome; D000077211:Zoledronic Acid
chemical_list: D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; D004164:Diphosphonates; D007093:Imidazoles; D010455:Peptides; D000077211:Zoledronic Acid; D000469:Alkaline Phosphatase