# Refractory Denosumab-induced Hypocalcemia in a High-risk Patient With Osteoblastic Metastatic Prostate Adenocarcinoma

## TL;DR

A high-risk patient with prostate cancer experienced severe, treatment-resistant low calcium levels after denosumab therapy, highlighting the need for better risk assessment and management strategies.

## Contribution

This case highlights refractory hypocalcemia in a high-risk patient on denosumab, emphasizing the need for improved risk stratification and treatment protocols.

## Key findings

- Denosumab-induced hypocalcemia in a high-risk patient did not respond to standard calcium and vitamin D supplementation.
- The patient required 64 days of hospitalization and calcitriol titration to stabilize calcium levels.
- Outcomes underscore the challenges in managing severe hypocalcemia in metastatic prostate cancer patients on denosumab.

## Abstract

Denosumab is a frequently used medication, mainly for the treatment of osteoporosis and prevention of skeletal-related events in patients with metastatic cancer. However, the treatment can be associated with adverse events including hypocalcemia.

We discuss the therapeutic challenges of denosumab-induced hypocalcemia in a patient with metastatic prostate adenocarcinoma. This 87-year-old patient presented to the emergency department after being found on the floor with altered mental status. Denosumab had been initiated 3 weeks earlier for stage 4 prostate adenocarcinoma with osteoblastic bone metastatic lesions. Blood analyses showed severe hypocalcemia (3.89 mg/dL [0.97 mmol/L]), which did not improve despite progressive incremental parenteral calcium administration and cholecalciferol supplementation. Management required 64 days of admission and titration of calcitriol. The patient was discharged after stabilizing plasma calcium level. Outpatient palliative care was later initiated because of progressive prostate adenocarcinoma, which ultimately led to the patient's death. Patients with metastatic bone disease, especially when treated with denosumab for prevention of skeletal-related events, present an increased risk of severe and even refractory hypocalcemia. More data are needed for optimal risk stratification of these patients, to identify robust predictors of hypocalcemia and to define the appropriate timing for starting calcium and vitamin D supplementation in high-risk individuals.