New Guidelines on Treating High Calcium Levels in People With Cancer

High calcium levels, called hypercalcemia by doctors, is the most common metabolic side effect in people diagnosed with cancer. The Endocrine Society, an international medical organization, has released the first guidelines on treating hypercalcemia in people diagnosed with cancer.

The guidelines were published online on Dec. 21, 2022, by The Journal of Clinical Endocrinology & Metabolism. Read “Treatment of Hypercalcemia of Malignancy in Adults: An Endocrine Society Clinical Practice Guideline.”

Hypercalcemia means the level of calcium in your blood is higher than normal. High blood calcium levels can weaken your bones, cause kidney stones, and affect how your heart and brain work.

Doctors estimate that hypercalcemia affects from 2% to 30% of people diagnosed with cancer. The condition is most common in people diagnosed with: 

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  breast cancer

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  lung cancer

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  kidney cancer (renal cancer) 

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  multiple myeloma (a cancer that forms in a type of white blood cell called a plasma cell)

Among those diagnosed with breast cancer, hypercalcemia often is seen in people with multiple areas of bone metastases, meaning the cancer has spread to a number of places in the bones. Still, some people without bone metastases also have hypercalcemia. This is because the breast cancer causes the immune system to secrete proteins that make certain bone cells called osteoclasts more active. Osteoclasts break down bone tissue, an important function in the life cycle of bones. Destruction of bone tissue can increase blood calcium levels.

Symptoms of hypercalcemia can include:

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  excessive thirst and urination

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  nausea

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  vomiting

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  constipation

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  bone pain

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  muscle weakness

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  fatigue

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  depression

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  heart problems

Hypercalcemia of malignancy is the term doctors use for people with hypercalcemia and cancer.

The guidelines were developed by a panel of experts who looked at all the available research.

To treat hypercalcemia in people diagnosed with cancer, the guidelines include the following recommendations:

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  Using an intravenous bisphosphonate or denosumab (brand names: Xgeva, Prolia) rather than not using these medicines. Bisphosphonates limit the activity of osteoclasts. Limiting the osteoclasts allows the osteoblasts — the bone-building cells — to work more effectively. Intravenous bisphosphonates include zoledronic acid (brand name: Reclast) and pamidronate (brand name: Aredia). Denosumab is a RANKL inhibitor, which means it blocks the RANKL protein, which also limits the activity of osteoclasts.

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  Using denosumab rather than a bisphosphonate.

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  Using a combination of calcitonin and an intravenous bisphosphonate or denosumab as the first treatment for people with severe hypercalcemia rather than using only an intravenous bisphosphonate or denosumab. Calcitonin is a hormone made by your thyroid gland that helps control how your body uses calcium. Calcitonin treatment should last for only 48 to 72 hours because the body stops responding to it.

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  Using denosumab if hypercalcemia recurs during intravenous bisphosphonate treatment.

“The recommendations provide a framework for the medical management of adults with [hypercalcemia of malignancy] and incorporate important decisional and contextual factors,” the researchers wrote. “The guidelines underscore current knowledge gaps that can be used to establish future research agendas.”

While you’re being treated for breast cancer, your medical team monitors you for a number of side effects. If your doctor doesn’t mention hypercalcemia to you, it’s a good idea to ask about it, especially if you have bone metastases.

It’s also important to tell your doctor if you have any symptoms of hypercalcemia, particularly symptoms related to kidney function, such as being extremely thirsty or urinating much more frequently than usual.

If you are diagnosed with hypercalcemia, these guidelines can help you and your doctor decide on the best treatment for you.