title: Effects of third generation aromatase inhibitors on bone health and other safety parameters: results of an open, randomised, multi-centre study of letrozole, exemestane and anastrozole in healthy postmenopausal women.
abstract: Given potential differences between the skeletal and other effects of the third generation aromatase inhibitors (AIs), we conducted an open, randomised Phase I study, comparing the effects of three licensed AIs on bone turnover markers, lipid profiles and adrenal function. Treatment comparisons were undertaken in 90 healthy postmenopausal women with normal bone mineral density who received once daily oral anastrozole (1mg, n=29), letrozole (2.5mg, n=29) or exemestane (25mg, n=32) for 24weeks with a subsequent 12week washout period. All three AIs induced increases in bone resorption markers, but no significant differences were observed in their effects on bone turnover markers. Greater differences were observed in lipid metabolism. Notably, exemestane, but not anastrozole or letrozole, significantly increased the LDL:HDL cholesterol ratio by 12weeks, largely mediated by a decrease in HDL-cholesterol. Further, long-term clinical studies are required to determine the impact, if any, of the differences observed between the AIs
authors.affiliation: Academic Unit of Bone Metabolism, University of Sheffield, Sorby Wing, Northern General Hospital, Herries Road, Sheffield S5 7AU, UK. e.v.mccloskey@shef.ac.uk
authors.forename: Eugene V
authors.initials: EV
authors.lastname: McCloskey
authors.forename: Rosemary A
authors.initials: RA
authors.lastname: Hannon
authors.forename: Geza
authors.initials: G
authors.lastname: Lakner
authors.forename: William D
authors.initials: WD
authors.lastname: Fraser
authors.forename: Glen
authors.initials: G
authors.lastname: Clack
authors.forename: Anna
authors.initials: A
authors.lastname: Miyamoto
authors.forename: Richard D
authors.initials: RD
authors.lastname: Finkelman
authors.forename: Richard
authors.initials: R
authors.lastname: Eastell
mesh_terms: D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism; D000469:Alkaline Phosphatase / Q000378:metabolism; D000077384:Anastrozole; D000730:Androstadienes / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D047072:Aromatase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D016723:Bone Remodeling / Q000187:drug effects; D001862:Bone Resorption / Q000139:chemically induced; D001842:Bone and Bones / Q000187:drug effects*; D005260:Female; D006801:Humans; D000077289:Letrozole; D008055:Lipids / Q000097:blood; D008875:Middle Aged; D009570:Nitriles / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D017698:Postmenopause / Q000097:blood / Q000187:drug effects*; D014230:Triazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*
chemical_list: D000730:Androstadienes; D047072:Aromatase Inhibitors; D015415:Biomarkers; D008055:Lipids; D009570:Nitriles; D014230:Triazoles; D000077384:Anastrozole; D000077289:Letrozole; D000469:Alkaline Phosphatase; C056516:exemestane