title: Zoledronic acid preserves bone mineral density in premenopausal women who develop ovarian failure due to adjuvant chemotherapy: final results from CALGB trial 79809.
abstract: BACKGROUND
  Chemotherapy-induced ovarian failure (CIOF) is a frequent side-effect of adjuvant chemotherapy that results in rapid bone loss. We hypothesised that zoledronic acid (ZA), a third-generation amino bisphosphonate, would prevent bone loss in premenopausal women who developed CIOF.
  
  
  METHODS
  Women (439) were randomised to intravenous (i.v.) ZA 4 mg every 3 months for 2 years starting within 1-3 months after randomization (arm A) or 1 year after randomization (arm B, controls). CIOF was prospectively defined as ≥ 3 months of amenorrhoea, follicle-stimulating hormone (FSH) ≥ 30 MIU/ml and non-pregnant at 1 year. The primary end-point was the percentage change in bone mineral density (BMD) in the lumbar spine (LS) from baseline to 12 months in the ZA and in control groups in women who developed CIOF; the secondary end-point was BMD in LS at 3 years in all randomised women.
  
  
  RESULTS
  One hundred and fifty (56%) met the definition of CIOF at 1 year. Overall, grade 3 toxicities of ZA were fatigue (1%) arthralgias (21%) and pain (84%). The median percent change (interquartile range, IQR) at 1 year was +1.2% (-0.5% to +2.8%) and -6.7% (-9.7% to -2.9%) p<0.001 and at 3 years was +1.0% (-1.6% to +5.2%) and -0.5% (-3.7% to +3.2%) p=0.019 in arms A and B, respectively.
  
  
  CONCLUSIONS
  ZA every 3 months is well tolerated and prevents rapid bone loss in premenopausal women that develop CIOF. Giving ZA with rather than 1 year after the start of adjuvant chemotherapy is the preferred sequence to prevent bone loss.
authors.affiliation: Ohio State University Medical Center and James Cancer Hospital, Columbus, OH 43210, USA. charles.shapiro@osumc.edu
authors.forename: C L
authors.initials: CL
authors.lastname: Shapiro
authors.forename: S
authors.initials: S
authors.lastname: Halabi
authors.forename: V
authors.initials: V
authors.lastname: Hars
authors.forename: L
authors.initials: L
authors.lastname: Archer
authors.forename: D
authors.initials: D
authors.lastname: Weckstein
authors.forename: J
authors.initials: J
authors.lastname: Kirshner
authors.forename: W
authors.initials: W
authors.lastname: Sikov
authors.forename: E
authors.initials: E
authors.lastname: Winer
authors.forename: H J
authors.initials: HJ
authors.lastname: Burstein
authors.forename: C
authors.initials: C
authors.lastname: Hudis
authors.forename: C
authors.initials: C
authors.lastname: Isaacs
authors.forename: R
authors.initials: R
authors.lastname: Schilsky
authors.forename: E
authors.initials: E
authors.lastname: Paskett
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000009:adverse effects*; D015519:Bone Density / Q000187:drug effects*; D050071:Bone Density Conservation Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001943:Breast Neoplasms / Q000188:drug therapy; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects; D004164:Diphosphonates / Q000008:administration & dosage* / Q000009:adverse effects; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D005334:Fever / Q000139:chemically induced; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage* / Q000009:adverse effects; D007262:Infusions, Intravenous; D008875:Middle Aged; D010146:Pain / Q000139:chemically induced; D017697:Premenopause; D016649:Primary Ovarian Insufficiency / Q000139:chemically induced*; D011446:Prospective Studies; D000077211:Zoledronic Acid
chemical_list: D000970:Antineoplastic Agents; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid