Prevention of anastrozole-induced bone loss with monthly oral ibandronate during adjuvant aromatase inhibitor therapy for breast cancer.
OBJECTIVE
The aromatase inhibitor anastrozole is a highly effective well-tolerated treatment for postmenopausal endocrine-responsive breast cancer. However, its use is associated with accelerated bone loss and an increase in fracture risk. The ARIBON trial is a double-blind, randomized, placebo-controlled study designed to evaluate the impact of bisphosphonate treatment on bone mineral density (BMD) in women taking anastrozole.


METHODS
BMD was assessed in 131 postmenopausal, surgically treated women with early breast cancer at two U.K. centers. Of these, 50 patients had osteopenia (T score -1.0 to -2.5) at either the hip or lumbar spine. All patients were treated with anastrozole 1 mg once a day and calcium and vitamin D supplementation. In addition, osteopenic patients were randomized to receive either treatment with ibandronate 150 mg orally every month or placebo.


RESULTS
After 2 years, osteopenic patients treated with ibandronate gained +2.98% (range -8.9, +19.9) and +0.60% (range -9.0, +6.9) at the lumbar spine and hip, respectively. Patients treated with placebo, however, lost -3.22% (range -16.0, +4.3) at the lumbar spine and -3.90% (range -12.3, +7.2) at the hip. The differences between the two treatment arms were statistically significant at both sites (P < 0.01). At 12 months, urinary n-telopeptide, serum c-telopeptide, and serum bone-specific alkaline phosphatase levels declined in patients receiving ibandronate (30.9%, 26.3%, and 22.8%, respectively) and increased in those taking placebo (40.3%, 34.9%, and 37.0%, respectively).


CONCLUSIONS
Monthly oral ibandronate improves bone density and normalizes bone turnover in patients treated with anastrozole.
Lester
James E
JE
Academic Unit of Clinical Oncology, Weston Park Hospital and Academic Unit of Bone Metabolism, University of Sheffield, Sheffield, United Kingdom. j.lester@sheffield.ac.uk
Dodwell
David
D
Purohit
Omprakash P
OP
Gutcher
Sandra A
SA
Ellis
Susan P
SP
Thorpe
Ruth
R
Horsman
Janet M
JM
Brown
Janet E
JE
Hannon
Rosemary A
RA
Coleman
Robert E
RE
D000368:Aged; D000077384:Anastrozole; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects; D047072:Aromatase Inhibitors / Q000494:pharmacology*; D015519:Bone Density; D050071:Bone Density Conservation Agents / Q000009:adverse effects; D001847:Bone Diseases / Q000139:chemically induced* / Q000150:complications*; D001943:Breast Neoplasms / Q000150:complications* / Q000188:drug therapy*; D004164:Diphosphonates / Q000008:administration & dosage*; D004311:Double-Blind Method; D005260:Female; D050723:Fractures, Bone / Q000139:chemically induced / Q000150:complications; D006801:Humans; D000077557:Ibandronic Acid; D008159:Lumbar Vertebrae / Q000187:drug effects / Q000473:pathology; D008875:Middle Aged; D009570:Nitriles / Q000009:adverse effects*; D010919:Placebos; D014230:Triazoles / Q000009:adverse effects*
D018931:Antineoplastic Agents, Hormonal; D047072:Aromatase Inhibitors; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D009570:Nitriles; D010919:Placebos; D014230:Triazoles; D000077384:Anastrozole; D000077557:Ibandronic Acid