Prolia Linked to Higher Hypocalcemia Risk Among Female Dialysis Patients: Study

Researchers warn that severe hypocalcemia can increase the risk of bone fractures, hospitalization and death for dialysis patients.

Side effects of the osteoporosis drug Prolia, when used to treat chronic kidney disease, may increase an individual’s risk of suffering from severely low calcium levels, according to the findings of a new study.

Researchers from the U.S. Food and Drug Administration (FDA) warn that patients taking Prolia had a 40% higher risk of low calcium and experienced side effects like bone fractures and hospitalization. Their findings were published on January 19, in the Journal of the American Medical Association (JAMA).

Prolia (denosumab) was first introduced in 2010, as the first drug ever approved by the FDA specifically to treat postmenopausal women with osteoporosis, who are at high risk for bone fracture. The drug’s use was later expanded to include approval for marketing as a treatment among men with osteoporosis, as well as women receiving aromatase inhibitor therapy for breast cancer.

The drug is administered through an injection by a healthcare professional once every six months, and is advertised to work by blocking a protein called RANK (receptor activator of nuclear factor kappa beta). Prolia also is designed to help the body prevent bone cells from breaking down bone in the body.

In this latest study, researchers from the FDA’s Office of Pharmacovigilance and Epidemiology, Center for Drug Evaluation and Research conducted a cohort study including 1,523 female dialysis-dependent Medicare patients over the age of 65, from 2013 to 2020. Patients were assigned to use 60 mg of Prolia or one of several oral bisphosphonates, such as Bondronat or Zometa.

Participants were then assessed for severe hypocalcemia, or abnormally low calcium in the body, which can lead to other side effects. Severe hypocalcemia is diagnosed at less than 7.5 mg/dl or in patients needing emergency care.

Overall, the findings indicate 41% of patients using Prolia developed severe hypocalcemia compared to 2% of bisphosphonate-treated patients. At the 12-week mark, 11% of Prolia patients suffered from very severe hypocalcemia compared to only 0.2% of the oral bisphosphonate patients.

The researchers determined taking Prolia increased the risk of suffering from very low calcium levels. Patients who had very severe hypocalcemia also suffered side effects like bone fractures, hospitalization, life-threatening events, and death.

“Given the complexity of diagnosing the underlying bone pathophysiology in dialysis-dependent patients, the high risk posed by [Prolia] in this population, and the complex strategies required to monitor and treat severe hypocalcemia, [Prolia] should be administered after careful patient selection and with plans for frequent monitoring,” the FDA researchers concluded.

Dialysis Bone Risks

Patients who have chronic kidney disease cannot filter the blood properly, often leading to excess fluid in the body and other health problems. They require dialysis to help filter the blood and remove toxins.

Nearly all chronic kidney disease patients who need dialysis also suffer from mineral and bone disorders requiring treatment from other medications.

Dialysis-dependent patients also often suffer from high rates of bone fractures, and the body relies on bone as a source of calcium. However, drugs like Prolia can also inhibit bone turnover, limiting the body’s ability to use bone calcium and complicating treatment.

In 2022, federal regulators investigated Prolia over concerns of bone fractures among chronic kidney disease patients undergoing dialysis.

Last month, the FDA issued a black box warning for Prolia over about the potential side effects of the drug, including the increased risk of severe hypocalcemia among kidney disease patients.