Risk Factors for Development of Hypocalcemia in Patients With Cancer Treated With Bone-Modifying Agents

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Paul S. White Section of Hematology and Oncology, Department of Medicine, and

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Michael Dennis Department of Medicine, Boston Medical Center; and

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Eric A. Jones Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts.

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Janice M. Weinberg Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts.

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Shayna Sarosiek Section of Hematology and Oncology, Department of Medicine, and

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Background: This retrospective analysis describes the prevalence of and risk factors associated with the development of hypocalcemia in patients with cancer receiving bone-modifying agents (BMAs) as supportive care. Patients and Methods: Patients with cancer treated with an intravenous or subcutaneous BMA, including pamidronate, zoledronic acid, or denosumab, at a tertiary care/safety net hospital in 2005 through 2015 were included in this retrospective review. We reviewed the medical records for predictive clinical and laboratory parameters and for patient outcomes. Results: A total of 835 patients with cancer received at least one dose of a BMA during the specified time frame; 205 patients (25%) developed hypocalcemia of CTCAE grade ≥1 within 8 weeks of BMA initiation, 18 of whom (8.8%) had grade ≥3, and 3 patients died as a result. Multivariate analysis showed that patients with hematologic malignancy (odds ratio [OR], 1.956; P=.025), bone metastases (OR, 2.443; P=.017), inpatient status (OR, 2.592; P<.001), and deficient baseline vitamin D levels (OR, 2.546; P<.023) were more likely to develop hypocalcemia. Hypercalcemia before BMA administration (OR, 0.474; P=.032) was protective. Conclusions: Certain patient populations, including those with hematologic malignancies and/or bone metastases, warrant closer monitoring of calcium levels while receiving BMAs because of the high rate of hypocalcemia. Low pretreatment vitamin D levels are associated with the development of hypocalcemia. These data support close monitoring of calcium levels in patients with cancer receiving BMAs, in addition to adequate repletion of vitamin D before initiation of BMAs when possible.

Submitted February 4, 2019; accepted for publication October 14, 2019.

Author contributions: Data collection and analysis: White, Dennis, Sarosiek. Statistical analyses: Jones, Weinberg. Manuscript preparation: White, Dennis, Sarosiek. Critical revision: Jones, Weinberg.

Disclosures: Dr. Weinberg has disclosed that she is a consultant for Janssen. The remaining authors have disclosed that they have not received any financial consideration from any person or organization to support the preparation, analysis, results, or discussion of this article.

Correspondence: Shayna Sarosiek, MD, Section of Hematology and Oncology, Department of Medicine, Boston Medical Center, FGH Building, 1st Floor, 820 Harrison Avenue, Boston, MA 02118. Email: shayna.sarosiek@bmc.org

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