Severe Refractory Hypocalcemia Caused by Denosumab

Dadana, Sriharsha; Gundepalli, Sai; Kondapalli, Anusha

doi:10.7759/cureus.39866

Cited by 2 publications

(1 citation statement)

References 16 publications

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“…Denosumab is an anti-receptor activator for nuclear factor-kB ligand monoclonal antibody that is administered to prevent skeletal-related events in patients with bone metastasis from solid tumors. However, denosumab-induced hypocalcemia is a well-known adverse event 1 and can have severe outcomes, [2][3][4][5] including tetany, seizures, and cardiac dysrhythmias. 6 The incidence of hypocalcemia can exceed 30%, [3][4][5]7 and severe cases (grade 3/4) account for approximately 10%.…”

Section: Introductionmentioning

confidence: 99%

External Validation and Update of the Risk Prediction Model for Denosumab-Induced Hypocalcemia Developed From a Hospital-Based Administrative Database

Ikegami,

Imai,

Yasumuro

et al. 2024

JCO Clin Cancer Inform

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PURPOSE Denosumab is used to treat patients with bone metastasis from solid tumors, but sometimes causes severe hypocalcemia, so careful clinical management is important. This study aims to externally validate our previously developed risk prediction model for denosumab-induced hypocalcemia by using data from two facilities with different characteristics in Japan and to develop an updated model with improved performance and generalizability. METHODS In the external validation, retrospective data of Kameda General Hospital (KGH) and Miyagi Cancer Center (MCC) between June 2013 and June 2022 were used and receiver operating characteristic (ROC)-AUC was mainly evaluated. A scoring-based updated model was developed using the same data set from a hospital-based administrative database as previously employed. Selection of variables related to prediction of hypocalcemia was based on the results of external validation. RESULTS For the external validation, data from 235 KGH patients and 224 MCC patients were collected. ROC-AUC values in the original model were 0.879 and 0.774, respectively. The updated model consisting of clinical laboratory tests (calcium, albumin, and alkaline phosphatase) afforded similar ROC-AUC values in the two facilities (KGH, 0.837; MCC, 0.856). CONCLUSION We developed an updated risk prediction model for denosumab-induced hypocalcemia with small interfacility differences. Our results indicate the importance of using data from plural facilities with different characteristics in the external validation of generalized prediction models and may be generally relevant to the clinical application of risk prediction models. Our findings are expected to contribute to improved management of bone metastasis treatment.

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Section: Introductionmentioning

confidence: 99%

External Validation and Update of the Risk Prediction Model for Denosumab-Induced Hypocalcemia Developed From a Hospital-Based Administrative Database

Ikegami,

Imai,

Yasumuro

et al. 2024

JCO Clin Cancer Inform

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Incidence and predictors of hypocalcemia in end-stage renal disease patients on denosumab therapy: A systematic review and meta-analysis

Siddiqui,

Shaikh,

Salman

et al. 2024

World J Meta-Anal

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BACKGROUND Denosumab inhibits the receptor activator of nuclear factor kappa-ligand. It markedly increases bone mineral density and has been proven to reduce the risk of fractures. However, numerous adverse effects, notably hypocalcemia, are prevalent in patients with end-stage renal disease (ESRD). AIM To analyze the incidence and predictors of hypocalcemia caused by denosumab compared to control in patients with ESRD. METHODS We conducted this study in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. PubMed, Scopus, Cochrane Central, and EMBASE were systematically searched from inception through March 2024. All original studies investigating the effects of denosumab on patients with ESRD compared to control were extracted. The primary outcomes of our study were the incidence of mild, severe, and very severe hypocalcemia. Secondary outcomes included serum levels of intact parathyroid hormone, calcium, and phosphate. The results were pooled and analyzed using a random-effects model. RESULTS Seven articles comprising 3240 patients were included in our study. Patients treated with denosumab had a significantly increased incidence of mild hypocalcemia [risk ratio (RR): 2.79; 95% confidence interval (CI): 0.99-7.91; P = 0.05; I ² = 37%] and of very severe hypocalcemia (RR: 9.58; 95%CI: 1.58-57.98; P = 0.01; I ² = 49%). However, an increase in the occurrence of severe hypocalcemia was non-significant (RR: 4.23; 95%CI: 0.47-38.34; P = 0.20; I ² = 96%). Alternatively, denosumab showed a significant decrease in serum intact parathyroid hormone [mean difference (MD): -433.20, 95%CI: -775.12 to -91.28, I 2 = 98%, P = 0.01], while there was a non-significant decrease in phosphate (MD: -0.47, 95%CI: -1.35 to 0.41, I 2 = 88%, P = 0.30) and calcium levels (MD: -0.33, 95%CI: -0.95 to 0.29, I 2 = 94%, P = 0.29). CONCLUSION Our study demonstrated that denosumab is significantly associated with mild and very severe hypocalcemia in patients with ESRD making it necessary to detect and prevent this side effect of treatment.

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Severe Refractory Hypocalcemia Caused by Denosumab

Cited by 2 publications

References 16 publications

External Validation and Update of the Risk Prediction Model for Denosumab-Induced Hypocalcemia Developed From a Hospital-Based Administrative Database

External Validation and Update of the Risk Prediction Model for Denosumab-Induced Hypocalcemia Developed From a Hospital-Based Administrative Database

Incidence and predictors of hypocalcemia in end-stage renal disease patients on denosumab therapy: A systematic review and meta-analysis

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