title: Predictors of skeletal complications in men with hormone-refractory metastatic prostate cancer.
abstract: OBJECTIVE
  Skeletal complications are a major cause of morbidity in men with hormone-refractory metastatic prostate cancer. These analyses were designed to identify the variables associated with a greater risk of skeletal complications.
  
  
  METHODS
  The 643 subjects in this report were participants in a randomized placebo-controlled trial to evaluate the effects of zoledronic acid on the incidence of skeletal-related events. All subjects had bone metastases and disease progression despite medical or surgical castration. The relationships between the baseline covariates and the time to the first skeletal-related event were assessed by Cox proportional hazard analyses. The serum bone-specific alkaline phosphatase (BAP) and urinary N-telopeptide level was assessed as a representative specific marker of osteoblastic and osteoclastic activity, respectively. The other covariates included in the model were age, cancer duration, Eastern Cooperative Oncology Group performance status, analgesic use, and prostate-specific antigen, hemoglobin, and lactate dehydrogenase levels.
  
  
  RESULTS
  Elevated BAP levels were consistently associated with a greater risk of adverse skeletal outcomes. Elevated BAP was significantly associated with a shorter time to the first skeletal-related event on multivariate analyses of the entire study population (relative risk 1.84, 95% confidence interval 1.40 to 2.43; P <0.001) and in subset analyses of the placebo and zoledronic acid groups. Elevated BAP levels were also consistently associated with adverse skeletal outcomes on multivariate analyses of the time to radiotherapy and pathologic fracture, the most common types of skeletal-related events in the study population. No other baseline variable was consistently associated with the risk of adverse skeletal outcomes.
  
  
  CONCLUSIONS
  The results of our study have shown that elevated serum BAP levels are associated with a greater risk of adverse skeletal outcomes in men with hormone-refractory prostate cancer and bone metastases.
authors.affiliation: Massachusetts General Hospital, Boston, Massachusetts 02114, USA. smith.matthew@mgh.harvard.edu
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Smith
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
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D001847:Bone Diseases / Q000209:etiology* / Q000517:prevention & control*; D001859:Bone Neoplasms / Q000556:secondary*; D002369:Castration; D004164:Diphosphonates / Q000627:therapeutic use*; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000150:complications* / Q000473:pathology* / Q000628:therapy; D017211:Treatment Failure; D000077211:Zoledronic Acid