Cancer Treatment-Induced Bone Loss in Patients with Breast Cancer: Pathophysiology and Clinical Perspectives

Hormone-ablative therapies for breast cancer can cause marked and rapid reductions in circulating estrogen levels. Cancer treatment-induced bone loss (CTIBL) is generally more rapid and severe than bone loss associated with menopause in women or aging in women and men. In premenopausal women with breast cancer, CTIBL is mainly caused by chemotherapy with resultant ovarian failure, through the use of gonadotropin-releasing hormone (GnRH) agonists or by tamoxifen. In postmenopausal women, steroidal and nonsteroidal aromatase inhibitors (AIs) increase bone turnover, decrease bone mass, and increase fracture rate. Oral bisphosphonates and intravenous zoledronic acid can prevent bone loss in pre- and postmenopausal women. Subcutaneous denosumab has been shown to increase bone mineral density significantly in postmenopausal women receiving AIs. Finally, there is increasing evidence to support a disease modifying effect of bone-targeted treatment with improvements in disease-free and overall survival in some disease settings.