SAT-751 - Abstract: Skeletal Protective Therapy Risk: A Case of Severe Antiresorptive Hypocalcemia

Background: Denosumab is a commonly used medication used to prevent skeletal related events in advanced metastatic prostate cancer with bony metastases due to its efficacy and renal safety profile. However, profound and persistent hypocalcemia may occur in patients with certain risk factors.

Case Description: An 80-year-old man with newly diagnosed metastatic prostate cancer was admitted to the hospital for worsening back pain and was found to have obstructive acute kidney injury. Initial laboratory work demonstrated corrected calcium of 8.5 mg/dL, alkaline phosphatase of 2,457U/L, and creatinine of 3.2 mg/dL. He was found to have extensive sclerotic bone disease on imaging and was treated with denosumab 120 mg subcutaneously for prevention of skeletal-related events. Calcium and vitamin D supplementation were also prescribed.

Results: Four days following denosumab, the patient developed persistent symptomatic hypocalcemia (lowest albumin-corrected calcium 6.5 mg/dL). Laboratory evaluation revealed an elevated PTH of 600.4 pg/mL, ALP of 2,405 IU/L, and a low 25-hydroxyvitamin D of 19 ng/mL. His hypocalcemia persisted for over six weeks, resulting in a prolonged hospitalization, despite intensive calcium management which included intermittent parenteral calcium infusion, high-dose oral calcium, calcitriol, and ergocalciferol. His calcium levels eventually stabilized with 1000 mg Calcium Citrate four times a day, calcitriol 3 mcg three times a day, achieving an albumin-corrected calcium of 7.8 mg/dL off parenteral calcium infusion; he was discharged on a high dose oral calcium and Vitamin D regimen. His calcium levels later normalized (corrected calcium 8.5 mg/dL), which allowed for the discontinuation of calcitriol and de-escalation of the calcium and vitamin D regimen.

Discussion: This case exemplifies how denosumab may induce hypocalcemia through a mechanism similar to hungry bone syndrome, particularly in patients with osteoblastic metastases and elevated alkaline phosphatase prior to treatment. In this setting, denosumab inhibits osteoclast-mediated bone resorption, while osteoblastic activity persists, leading to ongoing skeletal calcium uptake and a net reduction in serum calcium. Prior studies have demonstrated that elevated alkaline phosphatase is a predictor of denosumab-associated hypocalcemia.

Conclusion: This case highlights the importance of raising awareness among non-endocrine clinicians about population-specific risks of potent osteoclast inhibitors. Patients with osteoblastic metastases and high bone remodeling are susceptible to severe and prolonged hypocalcemia after denosumab therapy. Although denosumab is frequently favored due to its renal safety profile, efficacy, and convenience of subcutaneous administration, careful pre-treatment biochemical assessment is important to identify patients at high risk for hypocalcemia.

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