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Life-threatening sustained hypocalcemia following Denosumab use in metastatic prostate cancer
Kanchi Patell1, Kumar Ajay1, Abdul Rahman Al Armashi1
124241St Vincent Charity Medical Center, Cleveland, OH, USA.
Introduction:
Prostate cancer is the second most frequently diagnosed cancer among men worldwide in 2020. Skeletal-related events (SRE) like pathologic fracture or spinal cord compression are commonly seen in metastatic prostate cancer. Denosumab, a monoclonal antibody, acts by inhibiting osteoclast-mediated bone resorption in bone metastasis from solid tumors and reduces bone turnover and destruction. However, there is an increased risk of life-threatening denosumab-induced hypocalcemia with an incidence of 0.1 to 12.8%.
Case Report:
Our patient is a 69-year-old man with widespread skeletal metastatic disease from primary prostate cancer who presented to the hospital complaining of generalized fatigue and joint pain. Due to severe debilitating low back pain secondary to osteochondral lesions, the patient was started on Denosumab 120 mg. On presentation, serum calcium was found to be severely low at 5.9 mg/dl (serum calcium level prior to Denosumab was 9.1 mg/dl).
Management And Outcome:
Denosumab was discontinued immediately, and the patient was started on IV calcium gluconate. Repeat serum calcium level continued to be low at 6.7 likely due to the long elimination half-life of Denosumab (25-30 days). He was transferred to a long-term acute care facility for long-term IV calcium replacement, where he succumbed to illness six weeks later.
Discussion:
Denosumab, an anti-resorptive treatment for skeletal metastasis from solid tumors, is shown to cause severe life-threatening hypocalcemia. The maximum serum drug level of Denosumab reaches 7-21 days after administration. Sustained hypocalcemia is rare and life-threatening. Clinicians should use this medication with caution due to its unpredictable side effect profile.
Insights
Denosumab can cause severe, life-threatening hypocalcemia in prostate cancer patients with bone metastasis. Careful monitoring is crucial due to its unpredictable and dangerous side effect profile.
Area of Science:
- Oncology
- Pharmacology
- Nephrology
Background:
- Prostate cancer frequently metastasizes to bone, leading to skeletal-related events.
- Denosumab, a monoclonal antibody, inhibits osteoclast activity to reduce bone resorption in metastatic bone disease.
- A significant risk of denosumab-induced hypocalcemia exists, with reported incidences ranging from 0.1% to 12.8%.
Observation:
- A 69-year-old male with metastatic prostate cancer developed severe hypocalcemia (5.9 mg/dL) after initiating Denosumab treatment for debilitating back pain.
- Initial calcium levels were normal (9.1 mg/dL) prior to Denosumab administration.
- Despite immediate discontinuation and IV calcium gluconate, serum calcium remained critically low due to Denosumab's long elimination half-life (25-30 days).
Findings:
- Denosumab administration led to severe, sustained hypocalcemia.
- The patient required prolonged IV calcium replacement and ultimately succumbed to the complications six weeks later.
- This case highlights the potential for rare but life-threatening hypocalcemia associated with Denosumab therapy.
Implications:
- Clinicians must exercise extreme caution when prescribing Denosumab, particularly in patients with metastatic prostate cancer and pre-existing bone lesions.
- Close monitoring of serum calcium levels is essential following Denosumab administration, especially within the 7-21 day peak drug level window.
- The unpredictable and severe nature of Denosumab-induced hypocalcemia necessitates a thorough risk-benefit assessment for each patient.
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