Effects of steroidal and nonsteroidal aromatase inhibitors on markers of bone turnover in healthy postmenopausal women.
BACKGROUND
In contrast to nonsteroidal aromatase inhibitors, the steroidal aromatase inactivator exemestane does not have detrimental effects on bone in animal models. This study was designed to compare the effects of exemestane with the nonsteroidal aromatase inhibitors anastrozole and letrozole on serum and urine levels of biomarkers of bone turnover in healthy postmenopausal women.


METHODS
Changes in the concentrations of bone-turnover markers, estrogens, and lipids were assessed after daily administration of exemestane (25 mg), letrozole (2.5 mg), anastrozole (1 mg), or placebo for 24 weeks in healthy postmenopausal women. The primary end point was the percentage change from baseline in bone-turnover-marker levels at week 24. The baseline-adjusted area under the curve (AUC) for weeks 0-12 and 0-24 was calculated to evaluate changes in bone turnover over time, rather than at discrete time points.


RESULTS
Seventy-four (88%) of 84 randomized subjects were evaluable for bone-marker assays. Reductions in plasma estrogen levels and increases in bone-resorption markers were comparable for each aromatase inhibitor. Uniquely, exemestane consistently increased the percentage change from baseline in the level of serum procollagen type I N-terminal propeptide (PINP), a marker of bone formation, at week 24. In the active-treatment groups, the baseline-adjusted AUC at weeks 0-12 and 0-24 for PINP was significantly greater for exemestane than the other aromatase inhibitors.


CONCLUSIONS
Exemestane increased serum levels of the bone-formation marker PINP after 24 weeks, suggesting a specific bone-formation effect related to its androgenic structure. Potential effects on cortical bone and reduced fracture risk must be verified in a comparative clinical trial.
Goss
Paul E
PE
Massachusetts General Hospital, 55 Fruit Street, LRH 302, Boston, MA 02114, USA. pgoss@partners.org
Hadji
Peyman
P
Subar
Milayna
M
Abreu
Paula
P
Thomsen
Torben
T
Banke-Bochita
Jose
J
D000368:Aged; D000077384:Anastrozole; D000730:Androstadienes / Q000008:administration & dosage; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage; D047072:Aromatase Inhibitors / Q000008:administration & dosage*; D015415:Biomarkers / Q000097:blood; D015519:Bone Density / Q000187:drug effects*; D016723:Bone Remodeling; D001862:Bone Resorption; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D004967:Estrogens / Q000097:blood; D005260:Female; D006801:Humans; D000077289:Letrozole; D008055:Lipids / Q000097:blood*; D008593:Menopause; D008875:Middle Aged; D009570:Nitriles / Q000008:administration & dosage; D010446:Peptide Fragments / Q000097:blood; D010919:Placebos; D011347:Procollagen / Q000097:blood; D016037:Single-Blind Method; D013629:Tamoxifen / Q000627:therapeutic use; D014230:Triazoles / Q000008:administration & dosage
D000730:Androstadienes; D018931:Antineoplastic Agents, Hormonal; D047072:Aromatase Inhibitors; D015415:Biomarkers; D004967:Estrogens; D008055:Lipids; D009570:Nitriles; D010446:Peptide Fragments; D010919:Placebos; D011347:Procollagen; D014230:Triazoles; C047202:procollagen Type I N-terminal peptide; D013629:Tamoxifen; D000077384:Anastrozole; D000077289:Letrozole; C056516:exemestane
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