title: Impact of androgen suppression and zoledronic acid on bone mineral density and fractures in the Trans-Tasman Radiation Oncology Group (TROG) 03.04 Randomised Androgen Deprivation and Radiotherapy (RADAR) randomized controlled trial for locally advanced prostate cancer.
abstract: OBJECTIVE
  To study the influence of adjuvant androgen suppression and bisphosphonates on incident vertebral and non-spinal fracture rates and bone mineral density (BMD) in men with locally advanced prostate cancer.
  
  
  METHODS
  Between 2003 and 2007, 1071 men with locally advanced prostate cancer were randomly allocated, using a 2 × 2 trial design, to 6 months i.m. leuprorelin (androgen suppression [AS]) before radiotherapy alone ± 12 months additional leuprorelin ± 18 months zoledronic acid (ZdA), commencing at randomization. The main endpoint was incident thoraco-lumbar vertebral fractures, which were assessed radiographically at randomization and at 3 years, then reassessed by centralized review. Subsidiary endpoints included incident non-spinal fractures, which were documented throughout follow-up, and BMD, which was measured in 222 subjects at baseline, 2 years and 4 years.
  
  
  RESULTS
  Incident vertebral fractures at 3 years were observed in 132 subjects. Their occurrence was not increased by 18 months' AS, nor reduced by ZdA. Incident non-spinal fractures occurred in 72 subjects and were significantly related to AS duration but not to ZdA. Osteopenia and osteoporosis prevalence rates at baseline were 23.4 and 1.4%, respectively, at the hip. Treatment for 6 and 18 months with AS caused significant reductions in hip BMD at 2 and 4 years (P < 0.01) and ZdA prevented these losses at both time points.
  
  
  CONCLUSIONS
  In an AS-naïve population, 18 months of ZdA treatment prevented the sustained BMD losses caused by 18 months of AS treatment; however, the study power was insufficient to show that AS duration or ZdA influenced vertebral fracture rates.
authors: School of Medicine and Public Health, University of Newcastle, Radiation Oncology Department, Calvary Mater Newcastle, NSW, Australia.
authors: James W
authors: JW
authors: Denham
authors: Michael
authors: M
authors: Nowitz
authors: David
authors: D
authors: Joseph
authors: Gillian
authors: G
authors: Duchesne
authors: Nigel A
authors: NA
authors: Spry
authors: David S
authors: DS
authors: Lamb
authors: John
authors: J
authors: Matthews
authors: Sandra
authors: S
authors: Turner
authors: Chris
authors: C
authors: Atkinson
authors: Keen-Hun
authors: KH
authors: Tai
authors: Nirdosh Kumar
authors: NK
authors: Gogna
authors: Lizbeth
authors: L
authors: Kenny
authors: Terry
authors: T
authors: Diamond
authors: Richard
authors: R
authors: Smart
authors: David
authors: D
authors: Rowan
authors: Pablo
authors: P
authors: Moscato
authors: Renato
authors: R
authors: Vimieiro
authors: Richard
authors: R
authors: Woodfield
authors: Kevin
authors: K
authors: Lynch
authors: Brett
authors: B
authors: Delahunt
authors: Judy
authors: J
authors: Murray
authors: Cate
authors: C
authors: D'Este
authors: Patrick
authors: P
authors: McElduff
authors: Allison
authors: A
authors: Steigler
authors: Allison
authors: A
authors: Kautto
authors: Jean
authors: J
authors: Ball
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000008:administration & dosage / Q000009:adverse effects*; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000009:adverse effects*; D001315:Australia; D015519:Bone Density / Q000187:drug effects*; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D004164:Diphosphonates / Q000627:therapeutic use*; D005500:Follow-Up Studies; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009520:New Zealand; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016103:Spinal Fractures / Q000139:chemically induced* / Q000517:prevention & control; D016896:Treatment Outcome; D000077211:Zoledronic Acid
chemical_list: D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid
keywords: androgen suppression; bisphophonate; bone mineral density; fractures; prostate cancer