title: Chemical castration induced by adjuvant cyclophosphamide, methotrexate, and fluorouracil chemotherapy causes rapid bone loss that is reduced by clodronate: a randomized study in premenopausal breast cancer patients.
abstract: OBJECTIVE
  In the majority of premenopausal breast cancer patients, an adjuvant chemotherapy-induced early menopause occurs, which is known to be a strong predictor of osteoporosis. We present data on the effect of adjuvant cyclophosphamide, methotrexate, and fluorouracil (CMF) therapy on bone mineral density (BMD) and the efficacy of clodronate on the prevention of bone loss in 148 premenopausal breast cancer patients without skeletal metastases.
  
  
  METHODS
  Patients were randomized to receive oral clodronate 1,600 mg/d or to a control group. In addition, patients were treated with six cycles of CMF therapy. BMD of the lumbar spine and femoral neck was measured by dual-energy x-ray absorptiometry (DEXA) before therapy and at 1 and 2 years.
  
  
  RESULTS
  Changes in the BMD of lumbar spine and femoral neck were -5.9% and -2.0% without clodronate and -2.2% and +0.9% with clodronate at 2 years (P = .0005 and .017, respectively). Patients who developed amenorrhea after chemotherapy had a rapid bone loss, which was significantly reduced by clodronate. In controls, bone loss was 9.5% in the lumbar spine and 4.6% in the femoral neck, while in the clodronate group, bone loss was 5.9% and 0.4%, respectively, at 2 years. Patients with preserved menstruation had only marginal changes in BMD.
  
  
  CONCLUSIONS
  Chemotherapy-induced ovarian failure causes rapid bone loss in premenopausal breast cancer patients. Women older than 40 years are at particularly high risk. Clodronate significantly reduces this bone loss.
authors.affiliation: Department of Oncology, Medicine and Diagnostic Radiology, Helsinki University Hospital, Finland.
authors.forename: T
authors.initials: T
authors.lastname: Saarto
authors.forename: C
authors.initials: C
authors.lastname: Blomqvist
authors.forename: M
authors.initials: M
authors.lastname: Välimäki
authors.forename: P
authors.initials: P
authors.lastname: Mäkelä
authors.forename: S
authors.initials: S
authors.lastname: Sarna
authors.forename: I
authors.initials: I
authors.lastname: Elomaa
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D015519:Bone Density / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D017024:Chemotherapy, Adjuvant; D004002:Clodronic Acid / Q000008:administration & dosage / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D010053:Ovary / Q000187:drug effects* / Q000503:physiopathology*; D017697:Premenopause; D011446:Prospective Studies; D016896:Treatment Outcome
chemical_list: D004002:Clodronic Acid; D003520:Cyclophosphamide; D005472:Fluorouracil; D008727:Methotrexate