Hypercalcemia of Malignancy and Medication-Related Osteonecrosis of the Jaw Following Denosumab Discontinuation in Metastatic Breast Cancer: A Case Report

Hypercalcemia of malignancy (HCM) is a common and serious complication in patients with advanced cancer and is associated with significant morbidity and mortality. Standard long-term management of HCM relies on anti-resorptive therapies such as bisphosphonates and denosumab, both of which act by inhibiting osteoclast-mediated bone resorption but carry the risk of medication-related osteonecrosis of the jaw (MRONJ). This case illustrates a patient with metastatic breast cancer (MBC) who developed recurrent, severe hypercalcemia after discontinuing denosumab due to MRONJ, followed by profound hypocalcemia upon the initiation of zoledronic acid. This case presentation signifies the challenges of maintaining calcium homeostasis in interrupted anti-resorptive therapy and the risk of rebound hypercalcemia after denosumab withdrawal. Continued monitoring to manage calcium disturbances and skeletal complications is required in cancer patients at risk for or experiencing MRONJ.