What is the treatment for hypercalcemia?

Treatment of Hypercalcemia

Bisphosphonates (such as IV pamidronate and zoledronic acid) are the first-line treatment for hypercalcemia, especially in cases of moderate to severe hypercalcemia associated with malignancy. 1

Initial Assessment and Workup

• Measure intact parathyroid hormone (iPTH), parathyroid hormone-related protein (PTHrP), 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, calcium, albumin, magnesium, and phosphorus levels to determine the underlying cause 2
• Correct calcium for albumin using the formula: corrected Ca (mg/dL) = measured Ca (mg/dL) + 0.8 × (4.0 - albumin [g/dL]) 3
• Assess severity of hypercalcemia:
  • Mild: total calcium <12 mg/dL (<3 mmol/L)
  • Moderate: total calcium 12-13.5 mg/dL (3-3.4 mmol/L)
  • Severe: total calcium >13.5 mg/dL (>3.4 mmol/L) 4
• Evaluate for symptoms such as polyuria, polydipsia, nausea, confusion, vomiting, abdominal pain, myalgia, dehydration, and mental status changes 2

Treatment Algorithm

1. Hydration

• Parenteral hydration with normal saline is the initial treatment for symptomatic hypercalcemia 5
• Administer IV normal saline to correct hypovolemia and promote calciuresis 1
• Target urine output of approximately 2 L/day throughout treatment 3, 6
• Avoid overhydration, especially in patients with cardiac failure 6

2. Bisphosphonate Therapy

• For moderate to severe hypercalcemia (≥12 mg/dL or ≥3 mmol/L), administer IV bisphosphonates 1, 4
• Zoledronic acid 4 mg IV over no less than 15 minutes is the preferred bisphosphonate for hypercalcemia of malignancy 3
• Pamidronate is an alternative option, particularly in patients with renal impairment 6
• Bisphosphonates normalize calcium levels in approximately 60% of patients 7
• For patients with renal impairment (CrCl 30-60 mL/min), reduce zoledronic acid dose according to the following:
  • CrCl 50-60 mL/min: 3.5 mg
  • CrCl 40-49 mL/min: 3.3 mg
  • CrCl 30-39 mL/min: 3.0 mg 3

3. Additional Therapies Based on Cause and Severity

• For hypercalcemia due to vitamin D toxicity, granulomatous disorders, or some lymphomas, consider glucocorticoids 4, 8
• For patients with renal failure, consider denosumab and dialysis with calcium-free or low-calcium solution 4, 8
• Calcitonin may be used for rapid but short-term reduction in calcium levels 9, 10
• Furosemide should not be used until after volume repletion is achieved, and has limited efficacy in reducing calcium levels 7, 10

Special Considerations

• Monitor renal function with serum creatinine before each bisphosphonate dose 3
• For hypercalcemia of malignancy, treat the underlying cancer when possible 5
• For patients with primary hyperparathyroidism, parathyroidectomy may be considered depending on age, calcium level, and evidence of kidney or skeletal disease 4
• Avoid vitamin D supplements in patients with hypercalcemia, particularly in early childhood 1
• For patients with multiple myeloma or bone metastases, consider continuing bisphosphonate therapy for up to 2 years 1

Follow-up and Monitoring

• Monitor serum calcium, renal function, and electrolytes regularly to assess treatment effectiveness 5
• For hypercalcemia of malignancy treated with zoledronic acid, retreatment may be considered if calcium levels rise again, but wait at least 7 days between doses 3
• Administer oral calcium supplements (500 mg) and vitamin D (400 IU) daily for patients on long-term bisphosphonate therapy for multiple myeloma or bone metastases 3

Common Pitfalls to Avoid

• Don't administer diuretics before correcting hypovolemia 6
• Don't overlook the need to treat the underlying cause of hypercalcemia 4
• Don't use bisphosphonates without checking renal function first 3
• Don't delay treatment with bisphosphonates in symptomatic or severe hypercalcemia, as their hypocalcemic effect is delayed 9