From the Guidelines
Hypercalcemia is a serious condition that requires prompt treatment to prevent complications such as kidney stones, bone pain, cognitive impairment, cardiac arrhythmias, and in severe cases, coma or death. The risks associated with hypercalcemia include kidney stones, bone pain, cognitive impairment, cardiac arrhythmias, and in severe cases, coma or death 1. Treatment depends on the severity and underlying cause of hypercalcemia. For mild cases (calcium <12 mg/dL), increasing fluid intake and addressing the underlying cause may suffice. Moderate to severe hypercalcemia requires more aggressive intervention, starting with IV fluids (normal saline at 200-300 mL/hour) to promote calcium excretion. Medications include bisphosphonates like zoledronic acid (4 mg IV) or pamidronate (60-90 mg IV), which inhibit bone resorption and take effect within 2-4 days. Calcitonin (4-8 IU/kg SC every 12 hours) provides rapid but temporary relief. Loop diuretics like furosemide (20-40 mg IV) may be added after adequate hydration to enhance calcium excretion. Glucocorticoids such as prednisone (40-60 mg daily) are effective for vitamin D-mediated or certain malignancy-related hypercalcemia. Cinacalcet (30-90 mg daily) is useful for hyperparathyroidism. Dialysis may be necessary in severe cases with renal failure. Patients should avoid calcium-rich foods, vitamin D supplements, and thiazide diuretics during treatment. Regular monitoring of calcium levels, renal function, and electrolytes is essential throughout treatment to prevent complications and assess response 1. Some key points to consider in the treatment of hypercalcemia include:
- The use of bisphosphonates, such as zoledronic acid, as a first-line treatment for hypercalcemia of malignancy 1
- The importance of addressing the underlying cause of hypercalcemia, such as hyperparathyroidism or malignancy 1
- The need for regular monitoring of calcium levels, renal function, and electrolytes to prevent complications and assess response to treatment 1
- The potential use of cinacalcet in patients with hyperparathyroidism 1
- The importance of avoiding calcium-rich foods, vitamin D supplements, and thiazide diuretics during treatment 1
From the FDA Drug Label
Patients with hypercalcemia of malignancy must be adequately rehydrated prior to administration of zoledronic acid injection. Zoledronic acid injection should be used with caution with other nephrotoxic drugs. Standard hypercalcemia-related metabolic parameters, such as serum levels of calcium, phosphate, and magnesium, as well as serum creatinine, should be carefully monitored following initiation of therapy with zoledronic acid injection If hypocalcemia, hypophosphatemia, or hypomagnesemia occur, short-term supplemental therapy may be necessary. Zoledronic acid injection is excreted intact primarily via the kidney, and the risk of adverse reactions, in particular renal adverse reactions, may be greater in patients with impaired renal function. The risk of osteonecrosis of the jaw (ONJ) may increase with duration of exposure to bisphosphonates Severe and occasionally incapacitating bone, joint, and/or muscle pain has been reported in patients taking bisphosphonates, including zoledronic acid injection. Atypical subtrochanteric and diaphyseal femoral fractures have been reported in patients receiving bisphosphonate therapy, including zoledronic acid injection
The high calcium risks associated with hypercalcemia of malignancy can be managed with zoledronic acid injection, but it is essential to carefully monitor patients for potential adverse reactions, including:
- Renal impairment
- Osteonecrosis of the jaw (ONJ)
- Musculoskeletal pain
- Atypical subtrochanteric and diaphyseal femoral fractures Patients should be adequately rehydrated prior to administration, and standard hypercalcemia-related metabolic parameters should be carefully monitored following initiation of therapy 2.
From the Research
Risks of Hypercalcemia
- Hypercalcemia can lead to severe symptoms, including kidney damage, bone disease, and anemia 3
- Primary hyperparathyroidism and malignancy are responsible for greater than 90% of all cases of hypercalcemia 3
- Hypercalcemia of malignancy is typically rapid in onset, with higher serum calcium levels, and more severe symptoms 3
- Patients with hypercalcemia of malignancy often show marked anemia, but never have kidney calculi or metabolic acidosis 3
Treatment Options for Hypercalcemia
- Treatment of hypercalcemia should be started with hydration 3
- Loop diuretics may be required in individuals with renal insufficiency or heart failure to prevent fluid overload 3
- Calcitonin is administered for the immediate short-term management of severe symptomatic hypercalcemia 3
- Bisphosphonates, such as zoledronic acid or pamidronate, are typically required for long-term control of severe or symptomatic hypercalcemia 3, 4, 5
- Glucocorticoids are effective in hypercalcemia due to lymphoma or granulomatous diseases 3, 6
- Dialysis is generally reserved for those with severe hypercalcemia complicated with kidney failure 3
Management of Severe Hypercalcemia
- Severe hypercalcemia is a life-threatening condition that should be managed urgently 4
- Saline hydration, furosemide, and zoledronic acid can be effective in managing severe hypercalcemia secondary to primary hyperparathyroidism 4
- Zoledronic acid was more potent than saline hydration and furosemide in reducing serum calcium levels 4
- Pamidronate can also be effective in reducing serum calcium levels in patients with severe hypercalcemia caused by primary hyperparathyroidism 5
Long-term Management of Hypercalcemia
- Bisphosphonates are considered the drugs of choice for long-term management of hypercalcemia 7
- Calcitonin is preferable in the short-term control of severe hypercalcemia 7
- Calcimimetic agents can be used to control hypercalcemia in selected cases of primary hyperparathyroidism 7
- Denosumab, a fully humanized anti-RANKL antibody, may be effective in suppressing bone resorption in patients with malignancy-associated hypercalcemia 7