title: A phase 3, double-blind, randomised, parallel-group, placebo-controlled study of oral weekly alendronate for the prevention of androgen deprivation bone loss in nonmetastatic prostate cancer: the Cancer and Osteoporosis Research with Alendronate and Leuprolide (CORAL) study.
abstract: BACKGROUND
  Androgen-deprivation therapy (ADT) induces loss of bone mineral density (BMD) and increases the risk of fractures in patients with prostate cancer (PCa). We sought to determine whether a weekly dose of alendronate, an oral bisphosphonate, could reduce this unwanted side-effect.
  
  
  OBJECTIVE
  To assess whether once-weekly oral alendronate therapy would maintain or improve BMD in men initiating ADT for localised PCa.
  
  
  METHODS
  A multicentre, double-blind, randomised, placebo-controlled study, we included hormonally naïve PCa patients initiating ADT with leuprolide acetate 30 mg intramuscularly every 4 mo.
  
  
  METHODS
  Patients were randomised to receive either oral alendronate 70 mg once weekly or placebo for 1 yr. Both groups received daily calcium 1g and vitamin D 400 international units.
  
  
  METHODS
  Changes in BMD (at the lumbar spine [LS] and total hip [TH]) and bone markers.
  
  
  CONCLUSIONS
  One hundred ninety-one subjects were enrolled, and 186 were randomised between alendronate (n=84) and placebo (n=102). The alendronate group demonstrated a mean spine BMD increase of 1.7% compared with -1.9% in the placebo group (p<0.0001). Alendronate also increased the BMD at the hip (percent change: 0.7%) compared to placebo (-1.6%). Median urinary N-terminal crosslinking telopeptide of type I collagen (Ntx) values decreased by 3.5% in the alendronate group and increased by 16.5% in the placebo arm, even after adjusting for centre (p=0.510) and baseline urinary Ntx (p<0.0001). Bone-specific alkaline phosphatase (BSAP) decreased a median of 2.25% in the alendronate group and increased a median of 3.12% in the placebo arm, regardless of centre or baseline BSAP or other covariates (p<0.0001). The safety and tolerability profile was similar for the two treatment groups.
  
  
  CONCLUSIONS
  Although the study was closed early because of slow accrual, it showed that weekly oral alendronate prevented bone loss and increased bone mass in addition to decreasing bone turnover in patients initiating ADT for localised PCa, with few related side-effects.
authors.affiliation: Sunnybrook Health Sciences Centre, Toronto, Ontario M4N 3M5, Canada. laurence.klotz@sunnybrook.ca
authors.forename: Laurence H
authors.initials: LH
authors.lastname: Klotz
authors.forename: Irene Y
authors.initials: IY
authors.lastname: McNeill
authors.forename: Marlene
authors.initials: M
authors.lastname: Kebabdjian
authors.forename: Liying
authors.initials: L
authors.lastname: Zhang
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Chin
mesh_terms: D015502:Absorptiometry, Photon; D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D019386:Alendronate / Q000008:administration & dosage* / Q000009:adverse effects; D000469:Alkaline Phosphatase / Q000097:blood; D000704:Analysis of Variance; D000726:Androgen Antagonists / Q000008:administration & dosage / Q000009:adverse effects*; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000009:adverse effects*; D015415:Biomarkers / Q000097:blood; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002170:Canada; D016009:Chi-Square Distribution; D024042:Collagen Type I / Q000097:blood; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D006621:Hip Joint / Q000000981:diagnostic imaging / Q000187:drug effects; D006801:Humans; D007273:Injections, Intramuscular; D016729:Leuprolide / Q000008:administration & dosage / Q000009:adverse effects*; D008159:Lumbar Vertebrae / Q000000981:diagnostic imaging / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D010024:Osteoporosis / Q000097:blood / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000517:prevention & control*; D018579:Patient Selection; D010455:Peptides / Q000097:blood; D011237:Predictive Value of Tests; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal; D015415:Biomarkers; D050071:Bone Density Conservation Agents; D024042:Collagen Type I; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide; D000469:Alkaline Phosphatase; D016729:Leuprolide; D019386:Alendronate