THE USE OF ORAL BISPHOSPHONATES IN REFRACTORY SEVERE HYPERCALCEMIA AFTER DENOSUMAB CESSATION.

Abstract

Denosumab,a monoclonal IgG2 antibody,is used as neoadjuvant therapy for giant cell bone tumors, particularly in inoperable or metastatic cases. It targets the receptor activator of nuclear factor kappa-β ligand (RANKL),which is overexpressed in tumor stromal cells.However,denosumab treatment can lead to side effects such as hypocalcemia during treatment and rarely but malignant hypercalcemia after discontinuation. The unpredictable onset time and persistent course of hypercalcemia attacks increase the duration of hospitalization and the risk of complications.

Case: A 9-year-old girl with a giant cell bone tumor was treated with denosumab for diffuse tumor recurrence. Severe hypercalcemia occurred four months after completing therapy. Evaluation suggested "rebound-linked" hypercalcemia following denosumab discontinuation. IV bisphosphonate treatment normalized calcium levels initially, but hypercalcemia recurred, requiring repeated IV bisphosphonate administration. Oral alendronate was used weekly to prevent further attacks, resulting in stable calcium levels during follow-up.

Results: Rebound hypercalcemia, as an unpredictable recurrent episode at any time, is a potential complication of denosumab cessation, and requires close monitoring post-treatment. Children may be at higher risk due to their rapid bone cycle. In long-term follow-up, IV and oral biphosphonates can be used effectively in the management of especially life-threatening recurrent attacks.