title: Prognostic role of serum parathyroid hormone levels in advanced prostate cancer patients undergoing zoledronic acid administration.
abstract: BACKGROUND
  Secondary hyperparathyroidism is frequent in prostate cancer patients with bone metastases, and this condition is worsened by the administration of potent bisphosphonates. Serum parathyroid hormone (PTH) elevation can impair the efficacy of these drugs in terms of survival.
  
  
  METHODS
  The prognostic role of elevated serum PTH levels at baseline and after 3 months of zoledronic acid administration was assessed prospectively in 643 bone metastatic prostate cancer patients enrolled in a prospective randomized, placebo-controlled study.
  
  
  RESULTS
  On multivariate analysis, after adjusting for major prognostic factors and bone turnover markers, elevated baseline serum PTH level was negatively associated with overall survival (hazard ratio [HR], 1.448; 95% confidence interval [CI], 1.045-2.006; p < .03) in zoledronic acid-treated patients but not in placebo-treated patients. In patients with normal baseline PTH levels, there was a trend but insignificant association between zoledronic acid administration and a better survival outcome than with placebo (HR, 0.81; 95% CI, 0.65-1.01; p = .065), whereas a trend in the opposite direction was observed in patients with elevated PTH levels (HR, 1.45; 95% CI, 0.87-2.39; p = .151); interaction test, p = .040. Elevated serum PTH level after 3 months of zoledronic acid treatment was not significantly associated with survival outcome.
  
  
  CONCLUSIONS
  Secondary hyperparathyroidism has a negative prognostic impact in metastatic prostate cancer patients undergoing zoledronic acid administration. Counteracting elevated PTH levels by adequate doses of vitamin D may improve the efficacy of this drug.
authors.affiliation: Medical Oncology, Department of Clinical and Biological Sciences, University of Turin, Azienda Ospedaliera San Luigi, Orbassano, Italy. alfredo.berruti@gmail.com
authors.forename: Alfredo
authors.initials: A
authors.lastname: Berruti
authors.forename: Richard
authors.initials: R
authors.lastname: Cook
authors.forename: Fred
authors.initials: F
authors.lastname: Saad
authors.forename: Consuelo
authors.initials: C
authors.lastname: Buttigliero
authors.forename: Allan
authors.initials: A
authors.lastname: Lipton
authors.forename: Marco
authors.initials: M
authors.lastname: Tampellini
authors.forename: Ker-Ai
authors.initials: KA
authors.lastname: Lee
authors.forename: Robert E
authors.initials: RE
authors.lastname: Coleman
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Smith
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D050071:Bone Density Conservation Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000097:blood* / Q000188:drug therapy* / Q000556:secondary; D004164:Diphosphonates / Q000009:adverse effects / Q000627:therapeutic use*; D018450:Disease Progression; D004311:Double-Blind Method; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000097:blood / Q000139:chemically induced; D007093:Imidazoles / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010281:Parathyroid Hormone / Q000097:blood*; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000097:blood* / Q000188:drug therapy*; D016019:Survival Analysis; D000077211:Zoledronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D010281:Parathyroid Hormone; D000077211:Zoledronic Acid