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Original Article Comparison of the Effectiveness and Hypocalcemia Risk of Antiresorptive Agents in Patients with Hypercalcemia of Malignancy
Sung Hye Kong1orcid , Seung Shin Park2, Jung Hee Kim2, Sang Wan Kim3, Se Hyun Kim4, Jee Hyun Kim4, Chan Soo Shin2

DOI: https://doi.org/10.3803/EnM.2024.2132 [Epub ahead of print]
Published online: February 4, 2025
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1Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
2Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
3Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea
4Division of Hematology and Medical Oncology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
Corresponding author:  Sung Hye Kong, Tel: +82-31-787-8126, Fax: +82-31-787-7029, 
Email: shkong@snu.ac.kr
Received: 2 August 2024   • Revised: 20 September 2024   • Accepted: 29 October 2024
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Abstract

Background
Hypercalcemia of malignancy (HCM), a major metabolic complication of cancer, is often managed with bisphosphonates (BP) and, increasingly, with denosumab. We aimed to compare the effectiveness and safety of denosumab with that of BP, with or without calcitonin, in treating HCM.
Methods
This retrospective cohort study was conducted at a tertiary hospital from 2017 to 2022 and included 317 patients treated for HCM. Participants were divided into three treatment groups: denosumab, intravenous (IV) BP only, and IV BP combined with calcitonin. The primary outcomes measured were changes in calcium levels and the incidence of hypocalcemia. Analysis of covariance was used to adjust for age, sex, body mass index, creatinine level, type of malignancy, and the use of furosemide and steroids.
Results
The mean participant age was 65 years, and 37.5% were female. After adjustment, both denosumab and IV BPs were found to effectively lower calcium levels. Denosumab led to a decrease of 2.0 mg/dL (−15.9%), while IV BP alone resulted in a reduction of 1.8 mg/dL (−13.9%). The largest reduction, of 2.7 mg/dL (−20.9%), occurred with IV BP and calcitonin. Both denosumab and IV BP+calcitonin yielded their lowest calcium levels within 48 hours, whereas the IV BP only group reached a nadir within 72 hours. Despite these differences in treatment effectiveness, hypocalcemia occurred significantly less frequently in the denosumab group compared to the other groups.
Conclusion
Denosumab and IV BP were similarly effective in reducing calcium levels. However, IV BP combined with calcitonin yielded a more rapid and pronounced decrease.

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