What is the treatment for hypercalcemia?

From the Guidelines

Hypercalcemia treatment should be initiated with hydration, bisphosphonates, denosumab, steroids, and/or calcitonin, with zoledronic acid being the preferred bisphosphonate option. The treatment approach depends on the severity, cause, and symptoms of hypercalcemia [ 1 ]. For mild hypercalcemia, increasing fluid intake and addressing the underlying cause may be sufficient. However, for moderate to severe cases, initial treatment involves IV normal saline to promote calcium excretion, followed by loop diuretics like furosemide once the patient is well-hydrated.

Some key points to consider in hypercalcemia treatment include:

• Bisphosphonates, such as zoledronic acid, are effective for hypercalcemia due to malignancy or bone disorders [ 1 ].
• Calcitonin provides rapid but short-term calcium reduction [ 1 ].
• Denosumab can be used when bisphosphonates are contraindicated [ 1 ].
• Glucocorticoids help in cases caused by vitamin D excess or certain malignancies [ 1 ].
• Treatment should always address the underlying cause, such as hyperparathyroidism, malignancy, or medication effects, while monitoring renal function, electrolytes, and calcium levels throughout treatment [ 1 ].

It is essential to note that the treatment approach may vary depending on the specific cause of hypercalcemia, such as multiple myeloma or lung cancer [ 1 ]. However, the most recent and highest quality study [ 1 ] recommends zoledronic acid as the preferred bisphosphonate option for hypercalcemia treatment.

From the FDA Drug Label

Zoledronic acid injection is indicated for the treatment of hypercalcemia of malignancy defined as an albumin-corrected calcium (cCa) of greater than or equal to 12 mg/dL [3.0 mmol/L] 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 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). Retreatment with zoledronic acid injection 4 mg may be considered if serum calcium does not return to normal or remain normal after initial treatment.

Hypercalcemia Treatment with Zoledronic Acid:

• The recommended dose is 4 mg infused over no less than 15 minutes.
• Patients should be adequately rehydrated prior to administration.
• Serum creatinine should be assessed prior to each treatment.
• Retreatment may be considered if serum calcium does not return to normal after initial treatment, with a minimum of 7 days between treatments 2.
• Patients with mild or asymptomatic hypercalcemia may be treated with conservative measures, 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 in cases of PHPT, parathyroidectomy may be considered depending on age, serum calcium level, and kidney or skeletal involvement 3.
• Initial therapy for symptomatic or severe hypercalcemia consists of hydration and intravenous bisphosphonates, such as zoledronic acid or pamidronate 3, 4.
• 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.

Bisphosphonate Therapy

• Bisphosphonates are the most commonly used treatment for hypercalcemia of malignancy, with five bisphosphonates currently licensed in Europe for this indication: etidronate, clodronate, pamidronate, ibandronate, and zoledronate 4.
• The efficacy of bisphosphonates depends on the dose administered and initial serum calcium concentration, with pamidronate being studied in the greatest number of investigations and in the largest number of patients 4.
• Zoledronate has been shown to be more effective than pamidronate in some studies, with a longer duration of response 4.

Other Treatment Options

• Calcitonin may be used as a temporizing measure to rapidly reduce serum calcium levels, but its efficacy in normalizing serum calcium levels is poor 4, 5.
• Gallium nitrate may be a valuable treatment for hypercalcemia of malignancy, with high efficacy and few adverse events apart from renal toxicity 4.
• Combination therapy with glucocorticosteroid drugs, oral phosphates, and forced diuresis may be used to take advantage of multiple mechanisms of action 6.