Minimizing Bone Loss Related to Therapy with Aromatase Inhibitors

Integration of aromatase inhibitors (AIs) into adjuvant therapy improves disease-free survival for postmenopausal women with early-stage breast cancer. However, AIs are associated with loss of bone-mineral density (BMD) that escalates with duration of therapy. Such BMD loss is mediated by osteoclasts, which depend on the receptor activator of nuclear factor-κB ligand (RANKL) for their formation, function, and survival. RANKL stimulates osteoclast-mediated bone resorption by binding to its receptor, RANK, on preosteoclasts and osteoclasts. Previous reports have shown that denosumab — a humanized monoclonal antibody that inhibits bone resorption by binding to RANKL with high affinity and specificity — can augment bone mass in postmenopausal w…