Effects of steroidal and nonsteroidal aromatase inhibitors on markers of bone turnover in healthy postmenopausal women

Paul E Goss¹ , Peyman Hadji² , Milayna Subar³ , Paula Abreu³ , Torben Thomsen⁴ and Jose Banke-Bochita⁵

¹Massachusetts General Hospital, 55 Fruit Street, LRH 302, Boston, MA, 02114 USA

²Philipps-University of Marburg, Philipps-Universität, Biegenstr. 10, 35032, Marburg, Germany

³Pfizer Inc., 235 East 42nd Street, New York New York 10017-5755 USA

⁴CRS Clinical Research Services, Moenchengladbach GmbH, Hindenburgstrasse 306 41061 Moenchengladbach, Germany

⁵PAREXEL GmbH, Klinikum Westend, Haus 18, Spandauer Damm 115, D-14050 Berlin, Germany

author email corresponding author email

Breast Cancer Research 2007, 9:R52doi:10.1186/bcr1757


Published:	10 August 2007

Abstract

Introduction

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.

Conclusion

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.