From the Guidelines
Hypercalcemia is primarily caused by excess bone resorption from bone disease, malignancy, primary hyperparathyroidism, and other conditions, and should be treated with hydration, bisphosphonates, denosumab, steroids, and/or calcitonin, depending on the severity and underlying cause, as recommended by the most recent guidelines 1.
Causes of Hypercalcemia
The causes of hypercalcemia can be diverse, including:
- Excess bone resorption from bone disease, which can lead to the release of calcium into the blood 1
- Malignancy, particularly multiple myeloma, lung, breast, and blood cancers 1
- Primary hyperparathyroidism, where overactive parathyroid glands produce excess parathyroid hormone (PTH) 1
- Excessive vitamin D intake, which can lead to increased calcium absorption in the gut 1
- Certain medications, such as thiazide diuretics and lithium, which can affect calcium levels in the blood 1
- Granulomatous diseases, such as sarcoidosis, which can lead to increased vitamin D production and subsequent hypercalcemia 1
- Prolonged immobilization, which can lead to bone resorption and hypercalcemia 1
Treatment Options
Treatment of hypercalcemia depends on the severity and underlying cause, and may include:
- Hydration with intravenous fluids to promote calcium excretion 1
- Bisphosphonates, such as zoledronic acid, which can help reduce bone resorption and lower calcium levels 1
- Denosumab, which can help reduce bone resorption and lower calcium levels in bisphosphonate-resistant cases 1
- Steroids, such as prednisone, which can help reduce inflammation and lower calcium levels in cases of vitamin D-mediated hypercalcemia 1
- Calcitonin, which can provide rapid but short-term calcium reduction 1
- Long-term management of the underlying condition, such as parathyroidectomy for primary hyperparathyroidism or appropriate cancer therapy for malignancy-related 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. Consideration should be given to the severity of, as well as the symptoms of, tumor-induced hypercalcemia when considering use of zoledronic acid injection.
The causes of hypercalcemia are not explicitly stated in the provided drug labels, but it is mentioned that tumor-induced hypercalcemia is a condition being treated with zoledronic acid injection 2, 2. Hypercalcemia of malignancy is also mentioned as an indication for zoledronic acid injection 2, 2 and denosumab 3. The treatment options for hypercalcemia include:
- Zoledronic acid injection 2, 2
- Denosumab 3
- Conservative measures such as saline hydration, with or without loop diuretics 2, 2
From the Research
Causes of Hypercalcemia
- Primary hyperparathyroidism (PHPT) and malignancy are the most common causes of hypercalcemia, accounting for approximately 90% of cases 4
- Other causes of hypercalcemia include:
- Granulomatous disease such as sarcoidosis 4, 5
- Endocrinopathies such as thyroid disease 4, 6
- Immobilization 4, 7
- Genetic disorders such as familial hypocalciuric hypercalcemia 6, 7
- Medications such as thiazide diuretics, lithium, and supplements like calcium, vitamin D, or vitamin A 4, 6, 7
- Vitamin D intoxication 8, 5
- Hypercalcemia of malignancy 4, 5
Treatment Options for Hypercalcemia
- Mild hypercalcemia usually does not require acute intervention, but may be managed with observation or parathyroidectomy in cases of primary hyperparathyroidism 4
- Initial therapy for symptomatic or severe hypercalcemia consists of hydration and intravenous bisphosphonates such as zoledronic acid or pamidronate 4
- Glucocorticoids may be used as primary treatment for hypercalcemia due to excessive intestinal calcium absorption, such as in vitamin D intoxication or granulomatous disorders 4, 8
- Denosumab and dialysis may be indicated in patients with kidney failure 4
- Treatment of the underlying cause of hypercalcemia is essential to reduce serum calcium levels and improve symptoms 4