The U.S. FDA has issued a warning regarding denosumab (brand name: Prolia), a drug prescribed to treat bone loss and prevent fractures in people at high risk for those outcomes. A recent study showed that people with advanced chronic kidney disease (CKD), particularly those on dialysis, are at increased risk for severe hypocalcemia, abnormally low levels of calcium in the blood. Learn the risks and signs of hypocalcemia if you take Prolia.*

Denosumab/Prolia and CKD

Doctors prescribe denosumab/Prolia for adults at high risk for bone fracture, including those with osteoporosis, men taking androgen deprivation therapy (ADT) for prostate cancer, women taking aromatase inhibitor therapy for breast cancer, and CKD patients of all sexes.

CKD patients are at risk for bone disease and fractures because in order to maintain strong bones, the kidneys must sustain a certain balance of several hormones, vitamins, and minerals, including calcium, phosphorus, vitamin D, and parathyroid hormone. Kidneys that aren’t functioning properly are unable to maintain that balance.

What the researchers did and what they found

The study on which the new boxed warning is based involved nearly 3000 women, aged 65 and older, who were on dialysis. Of those, 1523 were given injections of 60 mg denosumab, and 1281 were given oral doses of bisphosphonates. 

After 12 weeks, the denosumab group experienced a much higher rate of severe hypocalcemia (defined as a serum calcium less than 7.5 mg/dL) than the bisphosphonates group (41.1% v. 2.0%), typically developing the hypocalcemia between two and 10 weeks following each administration of denosumab. 

What it means

Severe hypocalcemia can be life-threatening, resulting in:

• Seizures,
• Cardiac arrhythmia, and 
• Death.

Signs and symptoms of hypocalcemia can include:

• Confusion
• Facial twitching
• Fainting
• Irregular heartbeat
• Muscle spasms and/or weakness
• Tingling or numbness
• Seizures

It’s important to report any of these symptoms to your healthcare provider. Severe hypocalcemia can also be asymptomatic, however, so close monitoring of your blood calcium is essential.

“For patients with advanced kidney disease, especially those on dialysis treated with Prolia, frequent monitoring of calcium in the blood, especially for the first 2 to 10 weeks after each Prolia injection, is recommended,” said the FDA in its official statement. “The dose and type of calcium and vitamin D supplements that may be needed should be tailored to the patient.”

*Persaud, N. (2024, January 22). FDA Adds Boxed Warning on Denosumab for Patients With Advanced CKD. Renal and Urology News. https://www.renalandurologynews.com/news/nephrology/chronic-kidney-disease-ckd/fda-adds-boxed-warning-on-denosumab-for-patients-with-advanced-ckd/