title: Zoledronic acid inhibits adjuvant letrozole-induced bone loss in postmenopausal women with early breast cancer.
abstract: OBJECTIVE
  Treatment with aromatase inhibitors decreases bone mineral density (BMD) and may increase the risk of fractures in postmenopausal women with early-stage breast cancer. The addition of zoledronic acid to adjuvant letrozole therapy may protect against bone loss.
  
  
  METHODS
  Patients receiving adjuvant letrozole were randomly assigned to receive either upfront or delayed-start zoledronic acid (4 mg intravenously every 6 months). The delayed group received zoledronic acid when lumbar spine (LS) or total hip (TH) T score decreased to less than -2.0 or when a nontraumatic fracture occurred. The primary end point of this study was to compare the change in LS BMD at month 12 between the groups. Secondary end points included change in TH BMD and changes in serum bone turnover markers at month 12.
  
  
  RESULTS
  The upfront and delayed groups each included 301 patients. At month 12, LS BMD was 4.4% higher in the upfront group than in the delayed group (95% CI, 3.7% to 5.0%; P < .0001), and TH BMD was 3.3% higher (95% CI, 2.8% to 3.8%; P < .0001). In the upfront group, mean serum N-telopeptide and bone-specific alkaline phosphatase concentrations decreased by 15.1% (P < .0001) and 8.8% (P = .0006), respectively, at month 12, whereas concentrations increased significantly in the delayed group by 19.9% (P = .013) and 24.3% (P < .0001), respectively.
  
  
  CONCLUSIONS
  With 1 year of follow-up, results of the primary end point of the Zometa-Femara Adjuvant Synergy Trial (Z-FAST) indicate that upfront zoledronic acid therapy prevents bone loss in the LS in postmenopausal women receiving adjuvant letrozole for early-stage breast cancer.
authors.affiliation: Magee-Womens Hospital, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15123, USA. brufskyam@upmc.edu
authors.forename: Adam
authors.initials: A
authors.lastname: Brufsky
authors.forename: W Graydon
authors.initials: WG
authors.lastname: Harker
authors.forename: J Thaddeus
authors.initials: JT
authors.lastname: Beck
authors.forename: Robert
authors.initials: R
authors.lastname: Carroll
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Tan-Chiu
authors.forename: Christopher
authors.initials: C
authors.lastname: Seidler
authors.forename: John
authors.initials: J
authors.lastname: Hohneker
authors.forename: Leo
authors.initials: L
authors.lastname: Lacerna
authors.forename: Stephanie
authors.initials: S
authors.lastname: Petrone
authors.forename: Edith A
authors.initials: EA
authors.lastname: Perez
mesh_terms: D000328:Adult; D000368:Aged; D000469:Alkaline Phosphatase / Q000097:blood; D015519:Bone Density / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy*; D024042:Collagen Type I / Q000097:blood; D004164:Diphosphonates / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects / Q000627:therapeutic use*; D000077289:Letrozole; D008875:Middle Aged; D009570:Nitriles / Q000009:adverse effects*; D015663:Osteoporosis, Postmenopausal / Q000517:prevention & control*; D010455:Peptides / Q000097:blood; D014230:Triazoles / Q000009:adverse effects*; D000077211:Zoledronic Acid
chemical_list: D024042:Collagen Type I; D004164:Diphosphonates; D007093:Imidazoles; D009570:Nitriles; D010455:Peptides; D014230:Triazoles; C052929:collagen type I trimeric cross-linked peptide; D000077211:Zoledronic Acid; D000077289:Letrozole; D000469:Alkaline Phosphatase