Effects of third-generation aromatase inhibitors on bone

Low oestradiol levels in women are associated with decreased bone mineral density (BMD) and increased fracture risk. The third-generation aromatase inhibitors (AIs; anastrozole, letrozole, and exemestane) are used in the treatment of early and advanced breast cancer and act by substantially reducing oestrogen synthesis in postmenopausal women. However, due to their mechanism of action, there is concern regarding the long-term effects of these agents on bone, particularly when used in the adjuvant setting. In this paper, the currently available data on the effects of the third-generation AIs on markers of bone turnover, BMD, and fracture risk are reviewed, with the emphasis on results in the adjuvant treatment of early breast cancer. These data suggest that both the steroidal (exemestane) and non-steroidal (anastrozole and letrozole) AIs appear to affect bone turnover. Conclusions regarding any clinically relevant differences between these agents are difficult to make, and further data are awaited from long-term adjuvant use of these three agents in ongoing clinical studies. Postmenopausal women are at increased risk of osteoporosis and fracture, and the increasing use of AIs in the adjuvant treatment of postmenopausal breast cancer patients will require appropriate consideration of fracture risk, with the use of anti-osteoporotic therapies, if necessary.