Bone safety of aromatase inhibitors versus tamoxifen

Bone loss may be a potential side effect of implementing aromatase inhibitors in the adjuvant setting. Current evidence suggests a minor bone loss during treatment with the steroidal aromatase inhibitor exemestane compared to placebo and a nonsignificant increase in fracture rate during treatment with exemestane when compared to tamoxifen. Such a difference could be due to the bone-sparing effects of tamoxifen. For the nonsteroidal inhibitors letrozole and anastrozole, the MA17 study revealed a nonsignificant increase in fracture rate for letrozole compared to placebo. In contrast, both anastrozole and letrozole were found to significantly increase fracture rate compared to tamoxifen when administered as monotherapy or given sequentially. While an increased fracture rate may have detrimental effects, evidence suggests that enhanced bone loss may be preventable through careful bone mineral density (BMD) assessment and treatment with bisphosphonates.