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A Simple-to-Use Score for Identifying Individuals at High Risk of Denosumab-Associated Hypocalcemia in Postmenopausal Osteoporosis: A Real-World Cohort Study

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Abstract

Since denosumab-associated hypocalcemia occurs infrequently, data on its incidence and risk factors are limited. We aimed to evaluate risk factors and develop a useful score for identifying individuals at risk of denosumab-associated hypocalcemia. In this retrospective cohort, 790 consecutive female patients who received 60 mg denosumab at least once between 2016 and 2017 were analyzed. Based on biochemical records from a large-scale single-center, mild and moderate hypocalcemia were defined as albumin-corrected calcium (cCa) levels < 8.5 and < 8.0 mg/dL (< 2.12 and < 2.0 mmol/L), respectively. Mild and moderate hypocalcemia were observed in 8.2% and 1.0% patients, respectively. Patients who developed mild hypocalcemia had lower baseline cCa (8.9 vs. 9.3 mg/dL and 2.22 vs. 2.32mmo/L) and estimated glomerular filtration rate (75.0 vs. 83.2 mL/min/1.73 m2) and more frequent loop diuretic use (10.8% vs. 4.4%; all p < 0.05). In multivariate analysis, low baseline cCa (OR 1.29; 95% CI 1.20–1.40) and chronic kidney disease (CKD) stages 3b-5 were associated with elevated mild hypocalcemia risk (OR 2.92; 95% CI 1.38–6.20). Loop diuretics use was associated with mild hypocalcemia (OR 2.61; 95% CI 1.11–6.18) by univariate analysis, independent of baseline cCa and CKD stage. A scoring approach identified two risk groups: (1) patients without CKD (eGFR ≥ 45) and cCa < 8.5 mg/dL (2.12 mmol/L) and (2) patients with CKD (eGFR < 45) and cCa < 9.5 mg/dL (2.37 mmol/L).

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Data Availability

The datasets generated during and/or analyzed during the current study are not publicly available but are available from the corresponding author on reasonable request.

Code Availability (Software Application or Custom Code)

Data are available on request due to privacy or other restrictions.

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Acknowledgements

We specially thank Minheui Yu and Doori Cho, the members of the SENTINEL (Severance ENdocrinology daTa scIeNcE pLatform) team for technical assistance in searching and summarizing the relevant literature (4-2018-1215).

Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

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Author notes

  1. Kyoung Jin Kim and Namki Hong equally contributed to this study as the first authors.

Authors and Affiliations

  1. Department of Internal Medicine, Severance Hospital, Endocrine Research Institute, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea

    Kyoung Jin Kim, Namki Hong, Seunghyun Lee & Yumie Rhee

  2. Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea

    Kyoung Jin Kim

  3. Department of Internal Medicine, Wonju Christian Hospital, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea

    Miryung Kim

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  1. Kyoung Jin Kim
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Contributions

All authors participated in the study design, conducted the study, and contributed to data acquisition. NH, KJK, and YR drafted and revised the manuscript for important intellectual content and interpreted the data. All authors reviewed and approved the final manuscript.

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Correspondence to Yumie Rhee.

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All authors declare there are no conflicts of interest regarding this manuscript.

Ethical Approval

This study was approved by the Institutional Review Board of Severance Hospital (IRB number: 4-2020-0159).

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Kim, K.J., Hong, N., Lee, S. et al. A Simple-to-Use Score for Identifying Individuals at High Risk of Denosumab-Associated Hypocalcemia in Postmenopausal Osteoporosis: A Real-World Cohort Study. Calcif Tissue Int 107, 567–575 (2020). https://doi.org/10.1007/s00223-020-00754-8

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  • DOI: https://doi.org/10.1007/s00223-020-00754-8

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