What is the treatment for hypercalcemia?

From the Guidelines

Hypercalcemia should be treated with hydration, bisphosphonates, denosumab, steroids, and/or calcitonin, with zoledronic acid being the preferred bisphosphonate 1. The treatment approach for hypercalcemia depends on the severity of the condition and its underlying cause.

Key Considerations

• For mild hypercalcemia, adequate hydration and addressing the underlying cause may be sufficient.
• For moderate to severe hypercalcemia, initial management includes aggressive IV fluid rehydration with normal saline to promote calcium excretion, followed by loop diuretics like furosemide to enhance calcium excretion.
• Bisphosphonates, specifically zoledronic acid, are first-line medications for hypercalcemia of malignancy, as they have been shown to be effective in reducing calcium levels 1.
• Calcitonin provides rapid but short-term calcium reduction and can be used in conjunction with other treatments.
• Denosumab can be used for refractory cases, and dialysis may be necessary in severe cases with renal failure.

Treatment Priorities

• Treating the underlying cause is essential for long-term management, whether it's primary hyperparathyroidism, malignancy, or medication effects.
• Ongoing monitoring is necessary to prevent recurrence, as calcium levels typically normalize within 2-4 days of treatment initiation. The most recent and highest quality study, published in 2020, supports the use of zoledronic acid as the preferred bisphosphonate for treating hypercalcemia 1.

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. Patients who receive zoledronic acid injection should have serum creatinine assessed prior to each treatment Consideration should be given to the severity of, as well as the symptoms of, tumor-induced hypercalcemia when considering use of zoledronic acid injection. 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).

The treatment for hypercalcemia of malignancy with zoledronic acid injection is a single-dose intravenous infusion of 4 mg over no less than 15 minutes.

• Key considerations for treatment include:
  • Assessing serum creatinine prior to each treatment
  • Evaluating the severity and symptoms of tumor-induced hypercalcemia
  • Initiating vigorous saline hydration to restore urine output
  • Using conservative measures for mild or asymptomatic hypercalcemia, such as saline hydration with or without loop diuretics 2

From the Research

Hypercalcemia Treatment Overview

• Hypercalcemia is a condition that affects approximately 1% of the worldwide population, with mild cases often being asymptomatic and severe cases causing symptoms such as nausea, vomiting, dehydration, confusion, somnolence, and coma 3.
• The treatment of hypercalcemia depends on the underlying cause, with primary hyperparathyroidism (PHPT) and malignancy being the most common causes 3, 4.

Treatment Approaches

• Mild hypercalcemia usually does not require acute intervention, but severe hypercalcemia requires immediate treatment with hydration and intravenous bisphosphonates, such as zoledronic acid or pamidronate 3, 5.
• Glucocorticoids may be used as primary treatment when hypercalcemia is due to excessive intestinal calcium absorption (vitamin D intoxication, granulomatous disorders, some lymphomas) 3.
• In patients with kidney failure, denosumab and dialysis may be indicated 3.
• The use of furosemide has been shown to have little effect on calcium levels in patients with severe hypercalcemia secondary to PHPT, while zoledronic acid has been shown to be more potent 5.

Management of Severe Hypercalcemia

• Severe hypercalcemia is a life-threatening condition that requires urgent management, with the aim of reducing serum calcium levels and improving symptoms 5, 6.
• The treatment of severe hypercalcemia involves a multi-step approach, including:
  • Restoring normovolemia to prevent renal impairment
  • Restoring renal function and enhancing renal excretion of calcium
  • Dialysis
  • Inhibiting osteoclastic bone resorption
  • Reducing intestinal calcium absorption 6.
• Bisphosphonates are currently the drugs of choice in most patients with severe hypercalcemia, after adequate hydration 6.

Underlying Disease Treatment

• It is essential to identify and treat the underlying cause of hypercalcemia, whether it be PHPT, malignancy, or another condition 3, 4.
• The prognosis for asymptomatic PHPT is excellent with either medical or surgical management, while hypercalcemia of malignancy is associated with poor survival 3.