What are the treatment options for hypercalcemia?

From the Guidelines

Hypercalcemia should be treated with hydration, bisphosphonates, denosumab, steroids, and/or calcitonin, with zoledronic acid being the preferred bisphosphonate. The treatment of hypercalcemia depends on its severity, cause, and symptoms. For mild asymptomatic hypercalcemia, adequate hydration and addressing the underlying cause may be sufficient. For moderate to severe hypercalcemia, initial management includes aggressive intravenous fluid rehydration with normal saline at 200-300 mL/hour to increase calcium excretion.

Treatment Options

• Medications include bisphosphonates like zoledronic acid (4 mg IV over 15 minutes) or pamidronate (60-90 mg IV over 2-4 hours), which inhibit bone resorption and typically lower calcium levels within 2-4 days, lasting several weeks 1.
• Calcitonin (4-8 IU/kg SC/IM every 12 hours) provides rapid but short-term calcium reduction.
• For hypercalcemia due to hyperparathyroidism, cinacalcet (30-90 mg orally daily) may be used.
• Glucocorticoids like prednisone (40-60 mg daily) are effective for hypercalcemia caused by certain malignancies or granulomatous diseases.
• Denosumab (120 mg SC) is an option for refractory cases.
• Loop diuretics like furosemide may be used after adequate hydration to enhance calcium excretion.
• Dialysis is reserved for severe cases with renal failure or life-threatening hypercalcemia.

Key Considerations

• Treating the underlying cause, such as surgical removal of parathyroid adenomas or treatment of malignancy, is crucial for long-term management.
• The NCCN MM Panel members prefer zoledronic acid for treatment of hypercalcemia 1.
• Plasmapheresis should be used as adjunctive therapy for symptomatic hyperviscosity.
• Erythropoietin therapy may be considered for patients with anemia, especially those with renal failure. The most recent and highest quality study 1 supports the use of hydration, bisphosphonates, denosumab, steroids, and/or calcitonin for the treatment of hypercalcemia, with zoledronic acid being the preferred bisphosphonate.

From the FDA Drug Label

The maximum recommended dose of zoledronic acid injection in hypercalcemia of malignancy (albumin-corrected serum calcium greater than or equal to 12 mg/dL [3. 0 mmol/L]) is 4 mg. Vigorous saline hydration, an integral part of hypercalcemia therapy, should be initiated promptly and an attempt should be made to restore the urine output to about 2 L/day throughout treatment. Mild or asymptomatic hypercalcemia may be treated with conservative measures (i. e., saline hydration, with or without loop diuretics).

Treatment options for hypercalcemia include:

• Zoledronic acid injection 4 mg as a single-dose intravenous infusion over no less than 15 minutes
• Vigorous saline hydration
• Conservative measures (saline hydration, with or without loop diuretics) for mild or asymptomatic hypercalcemia
• Retreatment with zoledronic acid injection 4 mg may be considered if serum calcium does not return to normal or remain normal after initial treatment, after a minimum of 7 days 2, 2, 2

From the Research

Treatment Options for Hypercalcemia

The treatment of hypercalcemia is based on several factors, including the underlying cause, severity of symptoms, and presence of any complications. The following are some of the treatment options available:

• Hydration: The first step in treating hypercalcemia is to restore extracellular volume with intravenous saline solution 3, 4, 5, 6, 7.
• Loop diuretics: These may be required in individuals with renal insufficiency or heart failure to prevent fluid overload 4, 6, 7.
• Bisphosphonates: These are considered the drugs of choice for long-term management of hypercalcemia due to their ability to reduce bone resorption 3, 4, 5, 6, 7.
• Calcitonin: This is used for the immediate short-term management of severe symptomatic hypercalcemia due to its rapid onset of action 3, 4, 5, 6, 7.
• Glucocorticoids: These are effective in hypercalcemia due to lymphoma or granulomatous diseases, and may also be used in combination with calcitonin to prolong its calcium-lowering effect 3, 4, 6, 7.
• Denosumab: This is a fully humanized anti-RANKL antibody that may be used to suppress bone resorption in patients with malignancy-associated hypercalcemia 5.
• Parathyroidectomy: This may be considered in patients with primary hyperparathyroidism, depending on age, serum calcium level, and kidney or skeletal involvement 4.
• Dialysis: This is generally reserved for those with severe hypercalcemia complicated with kidney failure 4, 6.

Specific Treatment Approaches

The treatment approach may vary depending on the underlying cause of hypercalcemia. For example:

• In patients with primary hyperparathyroidism, treatment may involve parathyroidectomy or observation with monitoring 4.
• In patients with malignancy-associated hypercalcemia, treatment may involve bisphosphonates, calcitonin, or denosumab, depending on the severity of symptoms and presence of any complications 3, 4, 5, 7.
• In patients with granulomatous diseases, treatment may involve glucocorticoids 3, 4, 6, 7.