The CDC estimates that over 10 million Americans have osteoporosis. Another 43 million have “low bone mass.” Bones can become weak because of illness, nutritional deficiencies, low levels of estrogen and or testosterone and medications such as prednisone, acid-suppressing drugs and antidepressants. Weakened bones can lead to fractures. One of the more popular treatments involves injections of Prolia for osteoporosis every six months. The FDA has just announced plans for a black box warning that involves Prolia (denosumab) and very low calcium levels (hypocalcemia).
What Is Hypocalcemia and Why Is It So Worrisome?
Low calcium levels are a big deal. Hypocalcemia doesn’t always cause symptoms, but when it does, they can be severe. Irregular heart rhythms, seizures, confusion, fainting and uncontrollable muscle twitching are all possible. Some people die if calcium levels get too low.
Early warning signs of trouble would be muscle cramps in the back or legs. Very dry skin and brittle nails. Tingling of the lips and/or tongue. In fact, tingling is of concern wherever it occurs. Other signals of low calcium levels include hair that becomes coarser than usual, as well as problems with memory, depression and/or muscle spasms.
We recognize that many of these symptoms can be brought on by other conditions and are not specific to hypocalcemia. That said, anyone who has several of these complaints should request a blood calcium test.
Conditions that Trigger Low Calcium:
If the parathyroid gland is not working normally it can cause hypocalcemia. Low vitamin D levels may also be a culprit. If kidneys are not working well, your body may end up with a calcium deficit.
Let’s not forget medications. Corticosteroids like prednisone are a potential problem. So are bisphosphonate drugs for osteoporosis. And then there are the proton pump inhibitors (PPIs) for heartburn. When people take PPIs like esomeprazole (Nexium), lansoprazole (Prevacid) or omeprazole (Prilosec) for long periods of time, they may risk hypomagnesemia (low magnesium levels) and hypocalcemia (Clinical Nephrology. Case Studies, Jan. 4, 2024).
Prolia for Osteoporosis: Beware Hypocalcemia!
The manufacturer of Prolia has a heading on its website titled:
Important Safety Information
The very first item on the list is:
“Do not take Prolia® if you: have low blood calcium;”
The FDA’s Black Box Warning About Hypocalcemia:
A study in JAMA (Jan. 19, 2024) was titled “Severe Hypocalcemia with Denosumab Among Older Female Dialysis-Dependent Patients.”
The authors concluded:
“Denosumab was associated with a markedly higher incidence of severe and very severe hypocalcemia in female dialysis-dependent patients aged 65 years or older compared with oral bisphosphonates.”
The study, which included nearly 3,000 women on dialysis, found that at three months, 41 percent of those on Prolia had seriously low calcium levels. In comparison, only 2 percent of those on oral osteoporosis drugs developed hypocalcemia in that time frame.
An editorial in the same journal urged doctors to concentrate on preventing hypocalcemia in dialysis patients. The boxed warning FDA will require on the prescribing information should alert physicians to this serious risk. Although people on dialysis are at the highest risk, low calcium levels can occur in other patients as well.
The FDA Takes Action About Prolia for Osteoporosis:
On the exact day that the JAMA article was published, the FDA announced a “Boxed Warning” for:
“increased risk of severe hypocalcemia in patients with advanced chronic kidney disease taking osteoporosis medicine Prolia (denosumab)”
Here is the critical FDA warning:
“For patients considering Prolia for osteoporosis treatment, talk to your health care professional about your kidney function and the risk of severe hypocalcemia. Whether Prolia treatment is appropriate for patients with advanced CKD should be determined by a health care professional with expertise in the diagnosis and management of CKD-MBD, including renal osteodystrophy.
“For patients already taking Prolia for osteoporosis, maintain adequate calcium and vitamin D intake while receiving this medicine. Since your health care professional administers Prolia by subcutaneous injection every 6 months, you should discuss with them if you are at increased risk, and if so, whether continuing this treatment is best for you. If discontinuation of Prolia treatment is recommended, your health care professional may advise other measures to monitor for and minimize the risk of rebound fractures.
“Do not stop taking Prolia without talking with your health care professional as your risk of bone fracture, including in the spine, is increased after stopping, skipping, or delaying Prolia. Tell your health care professional if you develop symptoms suggestive of hypocalcemia such as confusion; seizures; irregular heart rhythm; fainting; face twitching; uncontrolled muscle spasms; or weakness, tingling, or numbness in parts of the body.”
Prolia for Osteoporosis and “Rebound Fractures”
Did the phrase “risk of rebound fractures” get your attention? It should have! We have become increasingly concerned about “rebound” problems when people stop taking a number of different drugs.
This reader wants to know what might happen if she had to stop Prolia for osteoporosis prevention:
Q. When I was in my early 40s I was diagnosed with serious osteoporosis. I did the prescribed exercises and took Fosamax for nearly 20 years.
When I was diagnosed with Barrett’s esophagus, I had to stop the alendronate (Fosamax). It can harm the esophagus, so I took PPIs to protect myself from cancer of the esophagus.
Since then, I have not used any medication for my bones. My PCP wants me to use Prolia. I am aware of the possible side effects. If I couldn’t tolerate it, would there be any risks to stopping?
A. You are right to be cautious. Stopping denosumab (Prolia), even just missing a dose, can lead to fractures of the vertebrae. If you had to stop the Prolia, you’d have to go on a bisphosphonate like alendronate right away to prevent the fracture risk. You have already had serious problems from this drug, so that might not be an option. Please assk your PCP to review all the other possible treatments for osteoporosis so you have an idea of your options.
Visitors to our website have shared some scary stories:
Terri shared this sad story after taking Prolia for osteoporosis:
“Why have you not covered the dangers of Prolia? I used it for 7 years without problem but then my doctors recommended I pause a 6-month dose to get oral surgery. NO ONE knew or told me that spontaneous multiple vertebral [spinal] fractures can happen when you discontinue Prolia without an alternative! I broke 5 vertebrae just 2 months after my missed dose. No one believed me until I got an MRI after 6 weeks of unrelenting pain. I’ve had two vertebroplasties, wear a back brace, and continue to have pain, taking opiates. I was healthy and very fit.
“I was shocked to find out on my own that multiple vertebral fractures can be caused from pausing Prolia injections! Neither my doctors nor my oral surgeon were aware that this could happen. I paused just one shot for oral surgery and have needed back surgery and am still in a back brace. Now I am in a “Prolia trap” where I can’t get off it for fear of more fractures. Osteoporosis drugs have ruined my life.”
Mary shared this about Prolia for osteoporosis:
“I recently found an article on the BetterBones website, written by Doctor Brown, titled “Is Prolia a blockbuster bone drug–or a bust.” She stated the finding that patients were more susceptible to having vertebral fractures after discontinuing Prolia than patients who’d never taken the drug at all. You can find this article with all the medical references, at her BetterBones site. I highly recommend it.”
Taking Prolia Forever?
The idea that a medicine could cause rebound spinal fractures after discontinuing it is disconcerting to say the least. Does that mean people who take Prolia for osteoporosis are destined to continue taking the medicine for life? If so, patients should be warned in advance.
Prolia for Osteoporosis Is Pricey!
According to the drug company that makes Prolia:
“The majority of commercial and Medicare plans cover Prolia®. The list price for Prolia® is $1,736.63 per injection every six months. Most patients do not pay the list price. Your actual cost will vary. Talk to your insurance provider.”
How much will patients have to pay for Prolia? Everything depends upon the kind of insurance people have.
Jodi relates this information about Prolia for osteoporosis:
“I recently had to pay over $700.00 to receive an injection of Prolia. This was my portion after Medicare and my supplemental insurance plan had paid their share.”
Another reader shared her complicated strategy:
“My doctor called in my prescription for Prolia. The drug cost $1,300.00 per prescription. I’ve been shopping around for help. An online company along with Walmart, discounted the price to $1,053.00. So I transferred my prescription from Walgreens to Walmart for the discount.
“How it works in my case: my doctor calls in the prescription, I go to the pharmacy and order the drug. The pharmacy notifies me when they receive it. Then I call my Dr’s office to schedule an appointment. When appt is made I then go to Walmart and pay for the drug, take it home, put it in my refrigerator to keep it at a certain temperature, then take it to the doctor’s office for them to inject the medicine in my arm.”
Other Prolia Side Effects:
The manufacturer lists “serious allergic reactions”:
“Call your doctor or go to your nearest emergency room right away if you have any symptoms of a serious allergic reaction, including low blood pressure (hypotension); trouble breathing; throat tightness; swelling of your face, lips, or tongue; rash; itching; or hives.”
Then there is osteonecrosis of the jaw:
“Your doctor should examine your mouth before you start Prolia® and may tell you to see your dentist. It is important for you to practice good mouth care during treatment with Prolia®.”
The drug company that makes Prolia for osteoporosis states:
“Unusual thigh bone fractures. Some people have developed unusual fractures in their thigh bone. Symptoms of a fracture include new or unusual pain in your hip, groin, or thigh.”
The whole reason to take an osteoporosis drug is to prevent fractures. That is why warnings about drug-related femur fractures or spinal fractures seems so paradoxical.
Other side effects we worry about include:
- Back pain
- Cystitis
- Pain in an extremity
- Bone pain
- Musculoskeletal pain
- Elevated cholesterol
- Vertigo
- Sciatica
Final Words:
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