The University of Connecticut Health Center
Translational Mechanisms of Bone Loss in Postmenopausal Women with Breast Cancer Undergoing Treatment with Aromatase Inhibitors
About this Project:
Aromatase inhibitors (AIs) are first line agents for the treatment of breast cancer and are known to cause a decrease in bone mineral density (BMD). Our study goal was to understand the translational mechanisms of bone loss in postmenopausal women on AIs for breast cancer. We hypothesized that decreases in estrogen with these agents would be associated with increased bone turnover and decreased BMD as a result of increased bone resorption, mediated by increased receptor activated nuclear factor kappa B (NF-kB) ligand (RANKL). Use of AIs in postmenopausal women with breast cancer was associated with a decrease in estrogen levels, a significant increase in bone resorption and formation, and a significant decrease in lumbar spine BMD. These changes occurred with a significant increase in RANKL levels and an increased RANKL/OPG ratio. The negative correlation between bone formation and BMD suggests that the intrinsic response of bone formation to increased resorption determines the magnitude of change in BMD in these women.