Denosumab Use in a Patient with Bisphosphonate-Resistant Humoral Hypercalcemia of Malignancy

ABSTRACT Objective: To describe the use of denosumab as an option for treating bisphosphonate-resistant humoral hypercalcemia of malignancy. Methods: We present the clinical history and laboratory findings of a patient with a review of related literature. Results: A 62 year-old male with stage IV laryngeal squamous cell carcinoma and lung metastases had multiple hospital admissions for asymptomatic hypercalcemia. The patient had no known bone metastases. His laboratory data showed a high calcium level, a low level of intact PTH and a high level of PTHrP, which confirmed the diagnosis of humoral hypercalcemia of malignancy. There was atypically an elevated level of 1,25(OH)2D. The patient was treated with fluids, prednisone, calcitonin, and bisphosphonates. Hypercalcemia was refractory to bisphosphonate treatment as well as other modalities. Denosumab treatment was then added. Denosumab along with bisphosphonate produced an added effect on lowering calcium levels. Conclusion: Denosumab provides potentially a new treatment option for bisphosphonate refractory humoral hypercalcemia of malignancy, especially in the presence of high PTHrP and 1,25(OH)2D. Abbreviations: PTH: Parathyroid Hormone, PTHrP: Parathyroid Hormone Related Peptide, HHM: Humoral Hypercalcemia of Malignancy. 1,25(OH)2D: 1,25-dihydroxyvitamin D. TSH: Thyroid stimulating hormone. RANKL: Receptor activator of nuclear factor kappa-B ligand. Key words: hypercalcemia, squamous cell carcinoma, malignancy, denosumab, bisphosphonate,1,25-dihydroxyvitamin D. This material presented in part at the American Association of Clinical Endocrinologists, 23rd Annual Scientific and Clinical Congress, No. 633, 2014