The effect of aromatase inhibitors on bone metabolism.

Aromatase inhibitors increase the disease-free survival in patients with receptor-positive breast cancer. Aromatase is a cytochrome P450 enzyme complex catalysing the conversion of androgens to oestrogens. These properties cause a significant increase in bone loss. In this MiniReview, we present data from the aromatase inhibitor studies and the studies designed to investigate aromatase inhibitor effect on bone metabolism. At the cellular level, oestrogen has profound effects on both osteoblasts and osteoclasts. Oestrogen decreases the osteoblastic production of resorptive cytokines and simultaneously increases the production of antireceptive cytokines, which leads to increased osteoclastic apoptosis and increased osteoblastic activity. Aromatase inhibitors inhibit the endogenous production of oestrogen by 50-90%. Studies designed to look at the effect of aromatase inhibitors on bone mineral density have shown a significant decrease in bone mineral density of the femoral neck in the aromatase inhibitor groups compared to placebo groups. Placebo-controlled studies lack statistical power to detect changes in fracture incidence; however, aromatase inhibitors increase the incidence of fractures in comparison with tamoxifen. We conclude that treatment with aromatase inhibitors leads to an increased bone loss and thus an increase in the risk of fractures in women with breast cancer.