Hypercalcemia is the most common metabolic complication associated with multiple myeloma. It can impact the disease process, outlook, and overall survival rate.

Multiple myeloma (MM) is a type of cancer affecting immune cells in the bone marrow called plasma cells. It is the second most common blood cancer after leukemia.

The condition is known for its tendency to destroy bones. This leads to complications that are responsible for increased rates of suffering and death associated with the disease.

Hypercalcemia, or having excess calcium in the blood, is a common cancer complication in the United States. But it is more common in people with MM, affecting approximately 30% of people with the condition at the time of diagnosis. High levels of calcium in the blood can sometimes be life threatening.

Pipette and test tubes for hypercalcemia diagnosis.Share on Pinterest

Bones have two types of cells that remodel bones to make them strong. Osteoclasts destroy old bones, while osteoblasts build bone, helping to maintain shape and integrity.

In MM, cancer cells produce substances that tell osteoclasts to speed up the rate they break down bone. This increases the levels of calcium in the blood.

The exact disease process is still not known, since not all people with MM develop hypercalcemia. It can be present at the time of diagnosis or develop later in the course of the disease. It mainly affects people with a significant volume of tumors. This is likely due to the bone-destroying activity of the cancer cells.

People with MM who also have hypercalcemia often have advanced-stage cancer. A 2016 review suggests that hypercalcemia is four times more likely to happen with stage 4 cancers and is associated with poor outcomes.

A 2020 study found that hypercalcemia is strongly associated with a poor outlook and earlier death.

It also frequently affects people with plasma cell leukemia, a late-stage complication of MM. According to a 2017 study, plasma cell leukemia is also associated with a poor outlook.

Hypercalcemia can also cause kidney stones and eventually cause permanent kidney damage. A 2021 study notes that kidney failure and infection are the leading cause of early death in people with MM.

A 2017 study of 2,129 people with MM mentioned that people with MM who have hypercalcemia may also have the following conditions:

In addition to these conditions, the researchers report that hypercalcemia was also associated with the presence of bone lesions and reduced kidney function. Of the 2,129 people with MM in the study, 19.5% presented with hypercalcemia at the time of diagnosis.

These conditions can complicate treatment and affect outlook.

A person with hypercalcemia may or may not show symptoms depending on the calcium levels in their blood and the rate of change of their blood concentration.

People with mild hypercalcemia may not have any symptoms. Symptoms may also be vague or nonspecific, such as:

Other symptoms may include:

Hypercalcemia may come on suddenly and be progressive. In some cases, it can cause a life threatening condition called a hypercalcemic crisis. This can lead to acute kidney failure and cause neurological symptoms from confusion to coma.

Generally, the treatment of hypercalcemia depends on the underlying cause and the severity of the disease. People with mild hypercalcemia without symptoms may not require treatment. But people with severe symptoms require prompt treatment.

The primary treatment for hypercalcemia is to treat the cancer. Although MM is an incurable condition, doctors may attempt to slow bone breakdown and improve calcium elimination in the kidneys.


Bisphosphonates are drugs that can reduce bone reabsorption by inhibiting osteoclasts, reduce bone turnover, and help pull excess calcium in the bloodstream into the bones.

Examples of bisphosphonates include:

  • pamidronate
  • zoledronic acid
  • ibandronate

Bisphosphonates can be toxic to the kidneys. Doctors only give them to people if the benefits outweigh the risks.

Discontinuing medications

Medications that can worsen hypercalcemia include:

Saline replenishment

People with hypercalcemia have abnormally low blood plasma volume because of excessive urination and vomiting.

This may make it harder for the body to eliminate calcium through urination and can worsen kidney injury. In some cases, this can even lead to kidney and heart failure.

To help prevent this from happening, the first-line treatment for hypercalcemia is fluid replacement through IV fluids.

Calcitonin and corticosteroids

Doctors may recommend calcitonin for quickly lowering calcium levels. This hormone inhibits the function of osteoclasts and boosts the excretion of calcium by the kidneys.

Corticosteroids help boost the effects of calcitonin, inhibit bone destruction, kill tumor cells, and decrease the activity and production of immune cells.

RANKL inhibitor

The receptor activator of nuclear factor-κB ligand (RANK) is one of the key mediators for bone resorption. RANKL inhibitors, such as denosumab, work by binding on RANK, decreasing bone breakdown through a loss of osteoclasts on the bone surface.

But these inhibitors may cause hypocalcemia and lower phosphate levels in the blood.


Hemodialysis is where a machine filters a person’s blood instead of the kidneys. The blood passes through a machine and a special filter, and small waste products in the blood, such as excess calcium, pass through this filter into a cleaning fluid called dialysate.

Some people with heart or kidney failure may not be able to tolerate high-volume fluid therapy. According to a 2014 study, in these cases, doctors may recommend hemodialysis with low levels or no amounts of calcium in the dialysate.

Learn more about dialysis here.

Hypercalcemia is the most common complication seen in people with MM. It is also associated with other complications, including kidney failure.

Hypercalcemia in people with MM is associated with poor outlook, including early death.

Not all people with MM develop hypercalcemia.