Aromatase inhibitors-induced bone loss in early breast cancer

Women with breast cancer have an increased prevalence and incidence of fractures. This increased risk of fracture has become most evident following the use of aromatase inhibitors (AIs) as standard adjuvant therapy. AI-induced bone loss occurs at more than twice the rate of physiologic postmenopausal bone loss. Moreover, peripheral quantitative computed tomography data indicate that effects of AIs on bone strength and on cortical bone have been substantially underestimated by dual-energy X-ray absorptiometry. All AIs have been associated with an increased fracture risk. The incidence of fractures is at least 33-43% higher in AI-treated patients than in tamoxifen-treated patients, and this increase in fracture risk is maintained at least for the duration of AI therapy. Over the last few years, clinical trials have established the effectiveness of bisphosphonates and denosumab to preserve and even increase bone mineral density (BMD) during adjuvant AIs. Most data have been obtained with zoledronic acid administered twice a year, which effectively maintains or increases BMD in women receiving AIs. In addition, zoledronic acid has been shown to delay disease recurrence and maybe prolong survival in women with hormone-responsive tumors, thereby providing an adjuvant antitumor benefit besides preserving BMD. It is likely that a combined fracture risk assessment will more accurately identify women with breast cancer who require bone protective therapy. The FRAX tool probably underestimates the net increase in fracture risk due to AI therapy. Recent guidelines for the prevention of AI-induced bone loss have adequately considered the presence of several established clinical risk factors for fractures, in addition to BMD, when selecting patients to be treated with inhibitors of bone resorption.