title: A RANKL Wrinkle: Denosumab-Induced Hypocalcemia.
abstract: The human monoclonal antibody denosumab inhibits osteoclast-mediated bone resorption by binding to receptor activator of nuclear factor κB ligand (RANKL), which is upregulated by tumor cells. Denosumab is indicated to prevent skeletal-related events (SREs) from osteoporosis and metastatic bone disease. We report a case of denosumab-induced hypocalcemia to highlight potential toxicity and treatment considerations. A 66-year-old man with prostate cancer, small cell lung cancer, and bone metastases presented with fatigue, weakness, and muscle spasm. Sixteen days prior, he received cycle 6 of cisplatin and etoposide, leuprolide, and denosumab (120 mg subcutaneously). His examination demonstrated a slight resting tremor, normal strength, and negative Chvostek sign. Laboratory analysis revealed hemoglobin, 8.0 g/dL; total calcium, 5.2 mg/dL (pre-denosumab, 8.9 mg/dL); and magnesium, 0.7 mg/dL. He initially received two units packed red blood cells, intravenous calcium and magnesium, and vitamin D. During his hospitalization, he required multiple doses of intravenous and oral calcium, magnesium, and vitamin D. Despite ongoing oral supplementation, his post-discharge serum calcium fluctuated significantly, requiring close monitoring and frequent dose adjustments. Denosumab's unique antiresorptive properties yield fewer SREs. The trade-off is increased hypocalcemia risk, which may be severe and require aggressive, prolonged supplementation and monitoring.
authors.affiliation: Ronald O. Perelman Department of Emergency Medicine, New York University School of Medicine, New York, NY, USA. larissala@gmail.com.
authors.forename: Larissa K
authors.identifier: 0000-0002-8491-1164
authors.initials: LK
authors.lastname: Laskowski
authors.affiliation: New York Harbor Veterans Affairs Medical Center and New York University Langone Medical Center Nephrology Section, New York, NY, USA.
authors.forename: David S
authors.initials: DS
authors.lastname: Goldfarb
authors.affiliation: Ronald O. Perelman Department of Emergency Medicine, New York University School of Medicine, New York, NY, USA.|College of Pharmacy and Health Sciences, St. John's University, Jamaica, NY, USA.
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Howland
authors.affiliation: Perlmutter Cancer Center, New York University, New York, NY, USA.
authors.forename: Kelly
authors.initials: K
authors.lastname: Kavcsak
authors.affiliation: Ronald O. Perelman Department of Emergency Medicine, New York University School of Medicine, New York, NY, USA.
authors.forename: Danny M
authors.initials: DM
authors.lastname: Lugassy
authors.affiliation: Ronald O. Perelman Department of Emergency Medicine, New York University School of Medicine, New York, NY, USA.
authors.forename: Silas W
authors.initials: SW
authors.lastname: Smith
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D050071:Bone Density Conservation Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary; D003131:Combined Modality Therapy; D000069448:Denosumab / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D006996:Hypocalcemia / Q000139:chemically induced* / Q000628:therapy; D008297:Male; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D016609:Neoplasms, Second Primary / Q000188:drug therapy; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D053245:RANK Ligand / Q000037:antagonists & inhibitors / Q000378:metabolism; D055752:Small Cell Lung Carcinoma / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D050071:Bone Density Conservation Agents; D009363:Neoplasm Proteins; D053245:RANK Ligand; C505688:TNFSF11 protein, human; D000069448:Denosumab
keywords: Adverse drug reaction; Cancer; Denosumab; Hypocalcemia; Toxicology