Bisphosphonates, which are also known as osteoclast modifiers, are the standard of care in the treatment of skeletal-related events (SREs) in patients with breast cancer with metastatic bone disease. SREs are frequently a complication of advanced breast cancer, and they greatly increase morbidity and mortality in these patients. Unfortunately, even while undergoing bisphosphonate therapy, many patients experience SREs. In 2010, a fully human monoclonal antibody, denosumab (Xgeva®), was approved by the U.S. Food and Drug Administration as another option to treat SREs.This article analyzes four primary human research studies looking at the effectiveness and safety of denosumab as compared to bisphosphonates in the prevention of SREs in this vulnerable population.Articles published from 2006-2012 were located and reviewed through online database searches (CINAHL®, MEDLINE®, PubMed Plus) using the key words denosumab, skeletal-related event, breast cancer, metastases, and bisphosphonates.Studies reviewed showed comparative adverse events and safety profile between denosumab and bisphosphonates. However, denosumab was shown to have increased effectiveness in the prevention of SREs. This knowledge can influence the preventive measures taken by physicians and advanced practice nurses to improve the prevention of SREs in patients with metastatic breast cancer. It can also increase staff nurse knowledge and implementation of evidence-based practice.