title: A single intravenous administration of zoledronic acid prevents the bone loss and mechanical compromise induced by aromatase inhibition in rats.
abstract: Recent evidence has demonstrated that long-term estrogen deprivation using aromatase inhibitor therapy in postmenopausal women with breast cancer results in bone loss and increased fracture risk. Bisphosphonates are potent inhibitors of bone resorption and have demonstrated efficacy in preventing bone loss in postmenopausal women with low bone mineral density (BMD) and in patients with breast cancer receiving estrogen deprivation therapy. Therefore, this study investigated the effects of the bisphosphonate zoledronic acid on BMD and bone strength in rats treated with the aromatase inhibitor, letrozole. Peripheral quantitative computed tomography demonstrated that treatment of rats with daily oral letrozole (1 mg/kg) induced significant bone loss and cortical thinning compared with control animals (P < 0.01). A single prior intravenous dose of zoledronic acid dose dependently protected against letrozole-induced bone loss and cortical thinning, with the highest evaluated dose (20 microg/kg) resulting in BMD values that were not significantly different from controls over the 24 weeks of letrozole treatment. Furthermore, biomechanical testing of the distal femoral metaphysis demonstrated that zoledronic acid (20 microg/kg) significantly prevented the decrease in stiffness and elastic modulus induced by letrozole treatment. Taken together, these data support the use of zoledronic acid for the prevention of bone loss in women with breast cancer receiving aromatase inhibitor therapy.
authors.affiliation: Novartis Institutes for BioMedical Research, Novartis Pharma AG, 4002 Basel, Switzerland. juerg.gasser@novartis.com <juerg.gasser@novartis.com>
authors.forename: Jürg A
authors.initials: JA
authors.lastname: Gasser
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Green
authors.forename: Victor
authors.initials: V
authors.lastname: Shen
authors.forename: Peter
authors.initials: P
authors.lastname: Ingold
authors.forename: Andrea
authors.initials: A
authors.lastname: Rebmann
authors.forename: Ajay S
authors.initials: AS
authors.lastname: Bhatnagar
authors.forename: Dean B
authors.initials: DB
authors.lastname: Evans
mesh_terms: D000818:Animals; D047072:Aromatase Inhibitors / Q000633:toxicity; D001696:Biomechanical Phenomena; D001835:Body Weight / Q000187:drug effects; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004164:Diphosphonates / Q000008:administration & dosage / Q000494:pharmacology*; D004967:Estrogens / Q000378:metabolism; D005260:Female; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D007275:Injections, Intravenous; D000077289:Letrozole; D009570:Nitriles / Q000633:toxicity; D009929:Organ Size / Q000187:drug effects; D015675:Osteocalcin / Q000097:blood; D010024:Osteoporosis / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D010052:Ovariectomy; D053245:RANK Ligand / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D014230:Triazoles / Q000633:toxicity; D014599:Uterus / Q000187:drug effects / Q000473:pathology; D000077211:Zoledronic Acid
chemical_list: D047072:Aromatase Inhibitors; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D004967:Estrogens; D007093:Imidazoles; D009570:Nitriles; D053245:RANK Ligand; D014230:Triazoles; D015675:Osteocalcin; D000077211:Zoledronic Acid; D000077289:Letrozole