title: Zoledronic acid prevents cancer treatment-induced bone loss in premenopausal women receiving adjuvant endocrine therapy for hormone-responsive breast cancer: a report from the Austrian Breast and Colorectal Cancer Study Group.
abstract: OBJECTIVE
  Adjuvant therapy for breast cancer can be associated with decreased bone mineral density (BMD) that may lead to skeletal morbidity. This study examined whether zoledronic acid can prevent bone loss associated with adjuvant endocrine therapy in premenopausal patients.
  
  
  METHODS
  This study is a randomized, open-label, phase III, four-arm trial comparing tamoxifen (20 mg/d orally) and goserelin (3.6 mg every 28 days subcutaneously) +/- zoledronic acid (4 mg intravenously every 6 months) versus anastrozole (1 mg/d orally) and goserelin +/- zoledronic acid for 3 years in premenopausal women with hormone-responsive breast cancer. In a BMD subprotocol at three trial centers, patients underwent serial BMD measurements at 0, 6, 12, 24, and 36 months.
  
  
  RESULTS
  Four hundred one patients were included in the BMD subprotocol. Endocrine treatment without zoledronic acid led to significant (P < .001) overall bone loss after 3 years of treatment (BMD, -14.4% after 36 months; mean T score reduction, -1.4). Overall bone loss was significantly more severe in patients receiving anastrozole/goserelin (BMD, -17.3%; mean T score reduction, -2.6) compared with patients receiving tamoxifen/goserelin (BMD, -11.6%; mean T score reduction, -1.1). In contrast, BMD remained stable in zoledronic acid-treated patients (P < .0001 compared with endocrine therapy alone). No interactions with age or other risk factors were noted.
  
  
  CONCLUSIONS
  Endocrine therapy caused significant bone loss that increased with treatment duration in premenopausal women with breast cancer. Zoledronic acid 4 mg every 6 months effectively inhibited bone loss. Regular BMD measurements and initiation of concomitant bisphosphonate therapy on evidence of bone loss should be considered for patients undergoing endocrine therapy.
authors.affiliation: Department of Surgery, General Hospital, Medical University of Vienna, Vienna, Austria. michael.gnant@meduniwien.ac.at
authors.forename: Michael F X
authors.initials: MF
authors.lastname: Gnant
authors.forename: Brigitte
authors.initials: B
authors.lastname: Mlineritsch
authors.forename: Gero
authors.initials: G
authors.lastname: Luschin-Ebengreuth
authors.forename: Stephan
authors.initials: S
authors.lastname: Grampp
authors.forename: Helmut
authors.initials: H
authors.lastname: Kaessmann
authors.forename: Marianne
authors.initials: M
authors.lastname: Schmid
authors.forename: Christian
authors.initials: C
authors.lastname: Menzel
authors.forename: Jutta Claudia
authors.initials: JC
authors.lastname: Piswanger-Soelkner
authors.forename: Arik
authors.initials: A
authors.lastname: Galid
authors.forename: Martina
authors.initials: M
authors.lastname: Mittlboeck
authors.forename: Hubert
authors.initials: H
authors.lastname: Hausmaninger
authors.forename: Raimund
authors.initials: R
authors.lastname: Jakesz
mesh_terms: D000328:Adult; D000077384:Anastrozole; D000970:Antineoplastic Agents / Q000009:adverse effects*; D047072:Aromatase Inhibitors / Q000009:adverse effects*; D015519:Bone Density / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy*; D004164:Diphosphonates / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D017273:Goserelin / Q000009:adverse effects*; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D009570:Nitriles / Q000009:adverse effects*; D015663:Osteoporosis, Postmenopausal / Q000517:prevention & control*; D013629:Tamoxifen / Q000009:adverse effects*; D014230:Triazoles / Q000009:adverse effects*; D000077211:Zoledronic Acid
chemical_list: D000970:Antineoplastic Agents; D047072:Aromatase Inhibitors; D004164:Diphosphonates; D007093:Imidazoles; D009570:Nitriles; D014230:Triazoles; D013629:Tamoxifen; D017273:Goserelin; D000077384:Anastrozole; D000077211:Zoledronic Acid