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 for treatment. The treatment approach for hypercalcemia involves a combination of these therapies, tailored to the severity and cause of the condition. Key considerations include:

• Hydration to increase calcium excretion
• Bisphosphonates, such as zoledronic acid, pamidronate, and ibandronate, to inhibit bone resorption, with zoledronic acid preferred due to its efficacy 1
• Denosumab for malignancy-related hypercalcemia resistant to bisphosphonates
• Steroids, like prednisone, for cases caused by certain cancers or granulomatous diseases
• Calcitonin for rapid, short-term calcium reduction It is essential to address the underlying cause of hypercalcemia, whether it be malignancy, hyperparathyroidism, or another condition, to achieve definitive treatment and improve patient outcomes, as outlined in the NCCN guidelines 1.

From the FDA Drug Label

Calcitonin-salmon injection is indicated for the early treatment of hypercalcemic emergencies, along with other appropriate agents, when a rapid decrease in serum calcium is required, until more specific treatment of the underlying disease can be accomplished The recommended starting dose of calcitonin-salmon injection for early treatment of hypercalcemia is 4 International Units/kg body weight every 12 hours by subcutaneous or intramuscular injection. Pamidronate disodium, in conjunction with adequate hydration, is indicated for the treatment of moderate or severe hypercalcemia associated with malignancy, with or without bone metastases. 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.

The treatment options for hypercalcemia include:

• Calcitonin-salmon injection: for early treatment of hypercalcemic emergencies, with a recommended starting dose of 4 International Units/kg body weight every 12 hours by subcutaneous or intramuscular injection 2
• Pamidronate disodium: for the treatment of moderate or severe hypercalcemia associated with malignancy, with or without bone metastases, in conjunction with adequate hydration 3
• Saline hydration: an integral part of hypercalcemia therapy, to restore urine output to about 2 L/day throughout treatment 3
• Other appropriate agents: may be used in conjunction with calcitonin-salmon injection for the treatment of hypercalcemia, such as intravenous fluids and furosemide, oral phosphate or corticosteroids 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 fluids, typically normal saline 4, 5, 6, 7, 8.
• Loop diuretics: These may be required in individuals with renal insufficiency or heart failure to prevent fluid overload 6, 7.
• Bisphosphonates: These are considered the drugs of choice for long-term management of hypercalcemia, particularly in cases of malignancy-associated hypercalcemia (MAH) 4, 5, 6, 7, 8.
• Calcitonin: This is used for the immediate short-term management of severe symptomatic hypercalcemia, and has a more rapid effect than bisphosphonates 4, 6, 8.
• Glucocorticoids: These are effective in hypercalcemia due to lymphoma or granulomatous diseases, and may also be used in cases of vitamin D intoxication 4, 5, 6.
• Parathyroidectomy: This is the only curative intervention for primary hyperparathyroidism, and may be considered in patients with symptomatic hypercalcemia due to this condition 5, 8.
• Denosumab: This is a fully humanized anti-RANKL antibody that may be used in cases of MAH, particularly in patients with renal insufficiency or those who have failed bisphosphonate therapy 7.
• Dialysis: This is generally reserved for patients with severe hypercalcemia complicated by kidney failure 6, 7.

Specific Treatment Approaches

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

• In cases of primary hyperparathyroidism, parathyroidectomy may be considered, particularly in patients with symptomatic hypercalcemia 5, 8.
• In cases of MAH, bisphosphonates and denosumab may be used to reduce bone resorption and lower serum calcium levels 5, 7.
• In cases of hypercalcemia due to vitamin D intoxication or granulomatous diseases, glucocorticoids may be effective in reducing serum calcium levels 4, 5, 6.

Monitoring and Follow-up

Regular monitoring of serum calcium levels and renal function is essential in patients with hypercalcemia, particularly in those receiving bisphosphonate therapy 5, 6, 7, 8.