Treatment of Hypercalcemia
The first-line treatment for hypercalcemia includes aggressive intravenous hydration with normal saline followed by bisphosphonate therapy, with zoledronic acid being the preferred agent for moderate to severe hypercalcemia, especially in malignancy-associated cases. 1, 2
Initial Assessment and Management
- Evaluate for underlying cause by measuring intact parathyroid hormone (iPTH), parathyroid hormone-related protein (PTHrP), vitamin D metabolites, calcium, albumin, magnesium, and phosphorus levels 1, 3
- Begin with aggressive intravenous normal saline to correct hypovolemia and promote calciuresis 1
- Maintain urine output of at least 100 ml/hour (3 ml/kg/hour in children <10 kg) 1
- Consider loop diuretics (furosemide) only after adequate hydration in patients with renal or cardiac insufficiency to prevent fluid overload 1, 4
Pharmacologic Therapy
Bisphosphonates
- Zoledronic acid (4 mg IV over no less than 15 minutes) is the preferred bisphosphonate for hypercalcemia of malignancy 1, 2
- For retreatment with zoledronic acid, wait a minimum of 7 days to allow full response to initial dose 2
- Adjust zoledronic acid dosing based on renal function:
- CrCl >60 mL/min: 4 mg
- CrCl 50-60 mL/min: 3.5 mg
- CrCl 40-49 mL/min: 3.3 mg
- CrCl 30-39 mL/min: 3 mg 2
- Pamidronate may be preferred over zoledronic acid in patients at higher risk for osteonecrosis of the jaw 4
Calcitonin
- Consider calcitonin (200 IU per day as nasal spray or 100 IU subcutaneously/intramuscularly every other day) for rapid but short-term reduction of calcium levels 1
- Most effective when combined with bisphosphonates due to its quick onset but limited duration of action (1-4 hours) 1, 5
Glucocorticoids
- Effective for hypercalcemia due to vitamin D-mediated conditions (sarcoidosis, lymphomas, vitamin D intoxication) 3, 6
- Not first-line therapy for malignancy-associated hypercalcemia unless related to lymphoma 6
Special Considerations
Malignancy-Associated Hypercalcemia
- For multiple myeloma patients, the National Comprehensive Cancer Network recommends hydration, furosemide, bisphosphonates, steroids, and/or calcitonin 4, 1
- Consider continuing bisphosphonate therapy for up to 2 years in patients with multiple myeloma or bone metastases 1
- Treat the underlying cancer when possible 3
Renal Impairment
- Monitor serum creatinine before each dose of bisphosphonate 2
- Avoid NSAIDs and intravenous contrast media in patients with renal impairment 1
- Consider denosumab or dialysis for patients with severe hypercalcemia complicated by renal failure 6, 5
Supportive Care
- Administer oral calcium supplements (500 mg) and vitamin D (400 IU) daily during bisphosphonate therapy to prevent hypocalcemia 2
- Avoid vitamin D supplements in patients with active hypercalcemia 1, 3
- Consider plasmapheresis as adjunctive therapy for symptomatic hyperviscosity in multiple myeloma 4, 1
Monitoring
- Regularly assess serum calcium, renal function, and electrolytes to evaluate treatment effectiveness 1, 3
- For patients receiving zoledronic acid, withhold treatment if renal function deteriorates:
- For normal baseline creatinine: increase of 0.5 mg/dL
- For abnormal baseline creatinine: increase of 1.0 mg/dL 2
Treatment Algorithm Based on Severity
Mild Hypercalcemia (Ca <12 mg/dL)
- Often asymptomatic and may not require acute intervention 5
- Ensure adequate hydration and treat underlying cause 6