Warnings Issued By The FDA For Popular Osteoporosis Drug And Its Serious Side Effects


In 2010, Prolia gained its initial approval for addressing osteoporosis in postmenopausal women at high risk of fractures. However, the FDA recently raised serious concerns regarding its usage, particularly in individuals with advanced chronic kidney disease.

Denosumab, marketed as Prolia, has triggered the FDA to issue a black box warning, denoting the gravest safety concerns. The crux of the matter lies in the potential for dangerously low levels of blood calcium, a condition known as severe hypocalcemia, in patients with advanced chronic kidney disease who are prescribed denosumab.

This January 19 statement from the FDA underscores the critical risks associated with denosumab intake for this specific patient population. Severe hypocalcemia poses life-threatening complications such as seizures and heart failure, prompting heightened caution and monitoring protocols for individuals undergoing treatment with Prolia, especially those with advanced chronic kidney disease.

“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,” the FDA had mentioned in the statement.

Signs of severe hypocalcemia, as outlined by the FDA, encompass a range of alarming manifestations such as confusion, seizures, fainting, facial twitching, uncontrollable muscle spasms, tingling or numbness in specific body areas, or irregular heart rhythms. Individuals undergoing denosumab treatment should promptly notify their healthcare provider if they encounter any of these symptoms, particularly if they have pre-existing conditions like chronic kidney disease or are undergoing dialysis, according to the FDA’s recommendations.

“Talk to your healthcare professional about specific instructions for the dose and type of calcium and vitamin D supplements that may be needed,” the FDA said. “Do not stop taking Prolia without talking with your healthcare professional, as your risk of bone fracture, including in the spine, is increased after stopping, skipping, or delaying Prolia.”

Safety Risks that Come with Denosumab

Upon scrutinizing studies predominantly conducted on Medicare patients utilizing denosumab, the FDA has discerned a notable escalation in the incidence of hypocalcemia among individuals prescribed this medication, relative to those using bisphosphonates, another class of drugs for osteoporosis management.

The regulatory body further examined 25 cases involving chronic kidney disease patients, some undergoing dialysis, who encountered complications of severe hypocalcemia subsequent to commencing denosumab treatment, as disclosed by the FDA. These complications ranged from cardiac arrhythmias to cognitive impairment, seizures, facial spasms, and muscular weakness or spasms.

A recent investigation published in JAMA on January 19 delved into the osteoporosis management of dialysis patients, revealing a significantly heightened risk of severe hypocalcemia among 1,523 individuals receiving denosumab, compared to 1,281 counterparts on bisphosphonates.

During the initial 12-week period of therapy, approximately 41 percent of denosumab recipients experienced severe hypocalcemia, in stark contrast to the mere 2 percent observed among those on bisphosphonates, as indicated by the study’s findings. This translates to a roughly 20-fold greater susceptibility to hypocalcemia with denosumab usage.

Reducing Risk for Fractures

People grappling with severe chronic kidney disease encounter a significant hurdle in assessing the value of denosumab due to the lack of conclusive evidence regarding its fracture-preventing efficacy, a characteristic shared with other osteoporosis medications. Thomas Nickolas, MD, a distinguished nephrology professor at Columbia University Irving Medical Center in New York City, highlights this challenge.

“There are clinical trials that have shown these medications will improve bone mineral density, which we assume translates into protection against fractures,” Dr. Nickolas said. However, since the benefit hasn’t been proven yet, there are other medicines for osteoporosis that people can opt for that don’t pose the same risk of severe hypocalcemia.

Moreover, Nickolas suggests that aside from medication, there exists a spectrum of actions individuals can undertake to bolster bone health and mitigate fracture risks. He emphasizes that individuals with advanced chronic kidney disease and those undergoing dialysis should adopt similar preventive measures as those unaffected by these conditions.

“For example, a healthy diet with adequate protein intake, weight-bearing exercise, limiting alcohol intake, and avoiding tobacco are universally good for the skeleton,” Nickolas said.

“Avoiding falls is also very important, and I counsel all my patients on fall prevention, including having night lights around the house, making sure rugs are not loose, making sure to slow down if they feel dizzy when going from sitting or lying to standing, and limiting exposure to medications that cause falls.”