Risk Analysis of Denosumab-Induced Hypocalcemia in Bone Metastasis Treatment: Renal Dysfunction Is Not a Risk Factor for Its Incidence in a Strict Denosumab Administration Management System with Calcium/Vitamin D Supplementation.

We have reported that a strict denosumab administration management system with oral calcium/vitamin D supplementation attenuates denosumab-induced hypocalcemia in 158 cancer patients with bone metastasis. In this report, 27.8% of the patients experienced hypocalcemia, including 0.6% with grade 2. So far, the risk factors for ≥grade 2 hypocalcemia incidence have been identified in denosumab-treated cancer patients, including patients without calcium/vitamin D supplementation. Therefore, the present study aimed to reveal the factors that affect all-grade hypocalcemia incidence with calcium/vitamin D supplementation and team medical care according to the management system. A receiver operating characteristic curve analysis suggested that the cutoff of baseline serum calcium level for all-grade hypocalcemia incidence was 9.3 mg/dL. Multivariate analysis revealed that age ≥65 years (odds ratio, 95% confidence interval: 2.57, 1.11-5.95, p = 0.03), grade 1 or higher serum alkaline phosphatase elevation (3.70, 1.71-8.00, p < 0.01), an adjusted serum calcium level of less than 9.3 mg/dL (3.21. 1.25-8.24, p = 0.02) at baseline, and co-administration of cytotoxic agents (2.33, 1.06-7.11, p = 0.03) are risk factors for the incidence of all-grade hypocalcemia. However, renal dysfunction, which has been suggested to be a risk factor in previous reports, was not a factor. In conclusion, we revealed the risk factors for all-grade hypocalcemia in calcium/vitamin D supplementation and awareness, as demonstrated by the management system. Moreover, renal dysfunction was not a risk factor in our strict denosumab administration management system. Our results support the value of early detection of hypocalcemia incidence to guide the selection of an appropriate management strategy.