title: A randomized phase II trial evaluating different schedules of zoledronic acid on bone mineral density in patients with prostate cancer beginning androgen deprivation therapy.
abstract: OBJECTIVE
  To assess the effects of timing and schedule of zoledronic acid (ZA) administration on bone mineral density (BMD) in patients beginning androgen deprivation therapy (ADT) for the treatment of recurrent prostate cancer.
  
  
  METHODS
  In this randomized, 3-arm trial, we evaluated changes in BMD after 3 different ZA administration schedules in men with recurrent prostate cancer who were beginning ADT. Forty-four patients were enrolled and randomized to receive a single dose of ZA given 1 week before beginning ADT (arm 1), a single dose of ZA given 6 months after beginning ADT (arm 2), or monthly administration of ZA starting 6 months after beginning ADT, for a total of 6 doses (arm 3).
  
  
  RESULTS
  Patients who received ZA before ADT had a significant improvement in BMD at the total proximal femur and trochanter after 6 months compared with the other groups. In addition, only patients in the arm that received multiple doses improved lumbar spine BMD while on ADT, with these findings persisting to 24 months. However, this group also experienced more grade 1 adverse events.
  
  
  CONCLUSIONS
  Analysis of these data suggests that ZA administration before initiation of ADT was superior to treatment 6 months after starting ADT in maintaining BMD. In addition, monthly ZA administration can increase BMD above baseline but is associated with more adverse events. Further study is needed to examine whether the timing and frequency of ZA therapy in patients on ADT can reduce fracture risk.
authors.affiliation: Department of Medicine, University of Wisconsin, Madison, WI; Carbone Cancer Center, University of Wisconsin, Madison, WI.
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Lang
authors.forename: Marianne
authors.initials: M
authors.lastname: Wallace
authors.forename: Jordan T
authors.initials: JT
authors.lastname: Becker
authors.forename: Jens C
authors.initials: JC
authors.lastname: Eickhoff
authors.forename: Bjoern
authors.initials: B
authors.lastname: Buehring
authors.forename: Neil
authors.initials: N
authors.lastname: Binkley
authors.forename: Mary Jane
authors.initials: MJ
authors.lastname: Staab
authors.forename: George
authors.initials: G
authors.lastname: Wilding
authors.forename: Glenn
authors.initials: G
authors.lastname: Liu
authors.forename: Miroslav
authors.initials: M
authors.lastname: Malkovsky
authors.forename: Douglas G
authors.initials: DG
authors.lastname: McNeel
mesh_terms: D000368:Aged; D000469:Alkaline Phosphatase / Q000097:blood; D000726:Androgen Antagonists / Q000627:therapeutic use; D015519:Bone Density / Q000187:drug effects*; D050071:Bone Density Conservation Agents / Q000009:adverse effects / Q000627:therapeutic use*; D049109:Cell Proliferation / Q000187:drug effects; D004164:Diphosphonates / Q000009:adverse effects / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D017273:Goserelin / Q000627:therapeutic use; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects / Q000627:therapeutic use*; D016729:Leuprolide / Q000627:therapeutic use; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D010024:Osteoporosis / Q000139:chemically induced / Q000188:drug therapy / Q000517:prevention & control*; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D013601:T-Lymphocytes / Q000187:drug effects; D000077211:Zoledronic Acid
chemical_list: D000726:Androgen Antagonists; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D017273:Goserelin; D000077211:Zoledronic Acid; D000469:Alkaline Phosphatase; D017430:Prostate-Specific Antigen; D016729:Leuprolide
keywords: Androgen deprivation; Bone mineral density; Gamma delta T cells; Prostate cancer; Zoledronic acid