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. The treatment of hypercalcemia depends on its severity, underlying cause, and symptoms. 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 increase renal calcium excretion 1.

Key Treatment Options

• Bisphosphonates, such as zoledronic acid, are first-line medications for hypercalcemia, particularly for malignancy-related hypercalcemia 1.
• Calcitonin provides rapid but short-term calcium reduction and works well with bisphosphonates.
• Denosumab may be used for refractory cases.
• Glucocorticoids like prednisone are effective for certain conditions like sarcoidosis or vitamin D toxicity.
• Loop diuretics, such as furosemide, can be added after adequate hydration.

Treatment Approach

The approach to treating hypercalcemia involves increasing urinary calcium excretion, inhibiting bone resorption, or reducing intestinal calcium absorption, depending on the medication used. According to the most recent guidelines, zoledronic acid is the preferred bisphosphonate for treating hypercalcemia 1. It is essential to consider the underlying cause of hypercalcemia and adjust the treatment accordingly.

Additional Considerations

In cases of severe hypercalcemia with renal failure or heart failure, hemodialysis may be necessary. The treatment should be tailored to the individual patient's needs, taking into account the severity of hypercalcemia, underlying cause, and symptoms. As stated in the guidelines, hydration, bisphosphonates, denosumab, steroids, and/or calcitonin are the recommended treatments for 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. 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). Patients should be hydrated adequately throughout the treatment, but overhydration, especially in those patients who have cardiac failure, must be avoided. Diuretic therapy should not be employed prior to correction of hypovolemia Retreatment with zoledronic acid injection 4 mg may be considered if serum calcium does not return to normal or remain normal after initial treatment.

The treatment for hypercalcemia includes:

• Zoledronic acid injection: 4 mg dose given as a single-dose intravenous infusion over no less than 15 minutes
• Saline hydration: vigorous hydration to restore urine output to about 2 L/day
• Conservative measures: saline hydration, with or without loop diuretics, for mild or asymptomatic hypercalcemia
• Retreatment: may be considered if serum calcium does not return to normal or remain normal after initial treatment, with a minimum of 7 days between treatments 2, 2 Alternatively, pamidronate disodium may be used in conjunction with adequate hydration for the treatment of moderate or severe hypercalcemia associated with malignancy 3

From the Research

Treatment Options for Hypercalcemia

The treatment for hypercalcemia depends on the severity and underlying cause of the condition.

• For mild hypercalcemia, treatment may not be necessary, but monitoring of serum calcium levels and observation may be appropriate 4.
• For symptomatic or severe hypercalcemia, initial therapy consists of hydration and intravenous bisphosphonates, such as zoledronic acid or pamidronate 4, 5, 6, 7.
• In patients with kidney failure, denosumab and dialysis may be indicated 4, 7.
• Glucocorticoids may be used as primary treatment when hypercalcemia is due to excessive intestinal calcium absorption (vitamin D intoxication, granulomatous disorders, some lymphomas) 4, 5, 6, 8.
• Calcitonin is administered for the immediate short-term management of severe symptomatic hypercalcemia 5, 6, 7.

Identifying the Underlying Cause

It is essential to identify and treat the underlying cause of hypercalcemia.

• Primary hyperparathyroidism and malignancy are responsible for greater than 90% of all cases of hypercalcemia 4, 5.
• Serum intact parathyroid hormone (PTH) is the most important initial test to evaluate hypercalcemia, distinguishing PTH-dependent from PTH-independent causes 4.
• Parathyroid hormone assay is the most useful test for differentiating hyperparathyroidism from malignancy and other causes of hypercalcemia 5.

Management of Hypercalcemic Crisis

In cases of hypercalcemic crisis, supportive care and ABC assessment are the first steps to preserve vital functions.

• The severity index criteria should be considered at admission, including severe dehydration, mental status alteration, renal impairment, cardiac arrhythmias, ionized calcium level, nausea or vomiting, and low social level 7.
• Five keystones in the treatment of the hypercalcemic crisis should be considered: restore normovolemia, restore renal function, dialysis, inhibit osteoclastic bone resorption, and reduce intestinal calcium absorption 7.