From the Guidelines
The treatment of hypercalcemia should be approached with hydration, bisphosphonates, denosumab, steroids, and/or calcitonin, with zoledronic acid being the preferred bisphosphonate. This approach is based on the most recent guidelines from the National Comprehensive Cancer Network (NCCN) 1. The initial management of hypercalcemia includes aggressive intravenous fluid rehydration with normal saline to restore intravascular volume and enhance renal calcium excretion.
Key Considerations
- For mild asymptomatic hypercalcemia, observation with adequate hydration may be sufficient.
- For moderate to severe hypercalcemia, initial management includes aggressive intravenous fluid rehydration with normal saline at 200-300 mL/hour.
- Loop diuretics like furosemide can be added to promote calcium excretion, but only after volume restoration.
- Bisphosphonates, such as zoledronic acid, are the mainstay of treatment for severe hypercalcemia or symptomatic cases.
- Calcitonin provides rapid but short-term calcium reduction and can be used while waiting for bisphosphonates to take effect.
- Denosumab can be considered in bisphosphonate-resistant cases.
Underlying Cause Consideration
The treatment should ultimately address the underlying cause of hypercalcemia, such as parathyroidectomy for primary hyperparathyroidism or treatment of malignancy for tumor-induced hypercalcemia. The NCCN guidelines emphasize the importance of treating the underlying cause of hypercalcemia, in addition to managing the symptoms and correcting the calcium levels 1.
Recent Guidelines
The most recent guidelines from the NCCN, published in 2020, recommend the use of zoledronic acid as the preferred bisphosphonate for the treatment of hypercalcemia 1. This recommendation is based on the efficacy and safety of zoledronic acid in reducing calcium levels and improving symptoms in patients with hypercalcemia.
Comparison with Other Studies
Other studies, such as those published in 2011 1 and 2009 1, also recommend the use of bisphosphonates, steroids, and calcitonin for the treatment of hypercalcemia. However, the 2020 NCCN guidelines are the most recent and provide the most up-to-date recommendations for the treatment of hypercalcemia. A study published in 2018 1 discusses the importance of avoiding hypercalcemia in patients with chronic kidney disease, but it does not provide specific recommendations for the treatment of hypercalcemia.
Clinical Decision
In clinical practice, the treatment of hypercalcemia should be individualized based on the severity of the condition, the underlying cause, and the patient's symptoms. The use of zoledronic acid as the preferred bisphosphonate, along with other treatments such as hydration, denosumab, steroids, and/or calcitonin, should be considered. The goal of treatment is to reduce calcium levels, improve symptoms, and address the underlying cause of hypercalcemia.
From the FDA Drug Label
- 2 Treatment of Hypercalcemia 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 It may also be added to existing therapeutic regimens for hypercalcemia such as intravenous fluids and furosemide, oral phosphate or corticosteroids, or other agents.
- 2 Hypercalcemia 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. If the response to this dose is not satisfactory after one or two days, the dose may be increased to 8 International Units/kg every 12 hours If the response remains unsatisfactory after two more days, the dose may be further increased to a maximum of 8 International Units/kg every 6 hours.
Treatment of Hypercalcemia: Calcitonin-salmon injection is indicated for the early treatment of hypercalcemic emergencies. The recommended starting dose is 4 International Units/kg body weight every 12 hours by subcutaneous or intramuscular injection, which can be increased to 8 International Units/kg every 12 hours or every 6 hours if the response is not satisfactory 2.
From the Research
Treatment of Hypercalcemia
The treatment of hypercalcemia depends on the severity and underlying cause of the condition.
- Mild hypercalcemia usually does not require acute intervention, but severe hypercalcemia can cause nausea, vomiting, dehydration, confusion, somnolence, and coma, and requires immediate treatment 3, 4.
- Initial therapy for symptomatic or severe hypercalcemia consists of hydration and intravenous bisphosphonates, such as zoledronic acid or pamidronate 3, 4, 5.
- In patients with kidney failure, denosumab and dialysis may be indicated 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, 4, 6.
Underlying Cause of Hypercalcemia
- The underlying cause of hypercalcemia should be identified and treated 3, 4, 5, 7.
- Primary hyperparathyroidism (PHPT) and malignancy are responsible for greater than 90% of all cases of hypercalcemia 3, 4, 7.
- Parathyroid hormone assay is the most useful test for differentiating hyperparathyroidism from malignancy and other causes of hypercalcemia 3, 4.
Management of Hypercalcemia
- Treatment reduces serum calcium and improves symptoms, at least transiently 3.
- The prognosis for asymptomatic PHPT is excellent with either medical or surgical management, while hypercalcemia of malignancy is associated with poor survival 3, 7.
- Asymptomatic hypercalcemia due to primary hyperparathyroidism is managed with parathyroidectomy or observation with monitoring, while severe hypercalcemia is typically treated with hydration and intravenous bisphosphonates 3, 4, 7.