Reclast vs. Prolia: Here’s How These Osteoporosis Injections Stack Up
Key takeaways:
Reclast (zoledronic acid) and Prolia (denosumab) are safe and effective medications for treating osteoporosis. They work in different ways, but both have been shown to reduce the risk of bone fractures (breaks).
Reclast is given as an intravenous (IV) infusion every 1 to 2 years. Prolia, on the other hand, is a twice-yearly injection that’s administered under the skin. They’re linked to slightly different side effects and drug interactions.
It’s important to take measures to avoid hypocalcemia (low calcium in the blood) with both Reclast and Prolia. It’s recommended for all people prescribed these medications to get enough calcium and vitamin D each day. Doing so helps promote bone health and prevent hypocalcemia.
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Table of contents
If you have osteoporosis, your body is either breaking down too much bone, not making enough new bone, or some combination of the two. Over time, this imbalance can lead to bone loss. Your bones could become weaker, less dense, and more prone to serious fractures as a result.
Whether you’re new to osteoporosis treatment, or are currently using other medications for osteoporosis, it’s important to know what treatment options are available.
Reclast (zoledronic acid) and Prolia (denosumab) are two convenient, long-acting injectables that treat osteoporosis. Let’s learn more about how they’re similar, how they’re different, and which of the two might be the best fit for you.
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Is Reclast or Prolia more effective for osteoporosis?
Reclast and Prolia are safe and effective osteoporosis medications. Studies show that Prolia and Reclast are generally just as effective as each other at reducing your risk for bone fractures (breaks).
The pair fights bone loss in different ways, though.
How does Reclast work?
Reclast belongs to a class of medications called bisphosphonates. Bisphosphonates decrease bone turnover to lower your risk of fractures.
Bone turnover is a natural and necessary process that happens when your bone is broken down and replaced with new bone. However, some health conditions and medications speed up bone breakdown or slow down bone-building. This can lead to osteoporosis and calcium loss from your bones.
Bisphosphonates primarily work on areas of your bone where turnover is high. This makes them especially useful for treating and preventing osteoporosis.
How does Prolia work?
Prolia is a biologic medication. Biologics are made from living or natural sources — such as proteins, blood, and various organisms. Biologics are typically more complex to produce than standard small molecule drugs. Biologics can also be more sensitive to changes in temperature and light.
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This biologic, Prolia, works by inhibiting a protein called RANKL. The cells responsible for breaking down bone need RANKL in order to work and survive. By stopping RANKL from binding to its receptor (chemical binding site), Prolia limits the ability of these cells to break down bone.
Prolia helps strengthen bones and boost bone mass by doing this. It helps reduce the risk of fractures. This is especially the case among women with osteoporosis who have gone through menopause. Prolia can also be prescribed to some people who don’t have osteoporosis but still have a high risk for fractures.
Injections vs. infusions for osteoporosis: How are Reclast and Prolia administered?
Reclast and Prolia are both administered relatively infrequently. This makes them more convenient to receive than medications that are taken daily or weekly. But there are some logistical differences between them.
Reclast, an infusion
Reclast is an intravenous (IV) infusion. It’s infused into a vein over at least 15 minutes per dose. You’ll receive it at an infusion clinic or another similar medical facility.
How often you’ll get this infusion depends on the reason you’re prescribed Reclast:
If you’re using Reclast to treat osteoporosis, you’ll likely receive a 5 mg infusion once yearly. This is also true if you’re using it to prevent osteoporosis from long-term corticosteroid use.
If you’re using Reclast to prevent postmenopausal osteoporosis, it’s typically given as a 5 mg infusion every 2 years.
While using Reclast, your rheumatologist will likely recommend taking calcium and vitamin D supplements. Anyone injecting Reclast is encouraged to take at least 1,200 mg of calcium and 800 international units (IU) of vitamin D daily. This is done to prevent hypocalcemia — or low calcium levels.
What’s more, after 3 to 5 years, your rheumatologist may tell you to stop your Reclast prescription. They’ll likely prescribe a different osteoporosis treatment for you instead. This is because Reclast’s clinical studies are based on 3 years of treatment.
Prolia, an injection
Prolia is given as an injection under your skin. It’s usually administered by a rheumatologist once every 6 months.
As with Reclast, preventing hypocalcemia is important with Prolia. Calcium and vitamin D supplements are generally recommended for everyone prescribed Prolia. It’s encouraged to take at least 1,000 mg of calcium and 400 IU of vitamin D daily with Prolia.
Certain people face a heightened risk of hypocalcemia, particularly those with chronic kidney disease undergoing dialysis.
What are common side effects of Reclast and Prolia?
While there are some similarities between the two medications as far as side effects and warnings go, there are also several differences.
Infusion-related reactions are common with Reclast. Such reactions are usually mild and include itching, headaches, or chills shortly after a dose. Your prescriber may recommend taking medications like Tylenol (acetaminophen) with your infusions to prevent these reactions. Injection-site reactions — such as redness or swelling around where you inject the medication — are more likely with Prolia.
Reclast side effects
The most common side effects of Reclast include:
Headache
Pain in your muscles or joints
Nausea and vomiting
Dizziness
Flu-like symptoms
Prolia side effects
The most common side effects of Prolia are:
Back pain
Higher cholesterol
Pain in the arms or legs
Muscle or joint pain
High blood pressure
Vertigo
Bladder infections
Serious side effects of both Reclast and Prolia
The more serious side effects of Reclast and Prolia are much less likely, but they can happen. With that in mind, it’s helpful to be aware of three possible risks of both medications:
Osteonecrosis of the jaw (ONJ): ONJ can cause your jawbone to weaken severely. It’s important to get a dental exam before starting Reclast or Prolia. This way, your dentist can assess your risk for developing ONJ.
Atypical fractures: If you notice new thigh, hip, or groin pain during treatment, it may be a sign of an atypical bone fracture. This is a fracture that happens without a known cause (like falling down). Let your rheumatologist know right away if this is the case.
Pain: Severe bone, joint, and muscle pain are possible side effects of both medications.
Who should not take Reclast or Prolia?
There are a few situations where you shouldn’t use Reclast or Prolia.
For instance, you shouldn’t receive Reclast or Prolia if you have pre-existing hypocalcemia. Ideally, hypocalcemia should be corrected before starting either one.
If you’re pregnant, you shouldn’t use Prolia or Reclast either. Both medications have the potential to cause harm to an unborn baby. Reclast and Prolia aren’t usually prescribed to women of child-bearing age as a result.
Avoid using Reclast, too, if you have acute kidney failure or severe kidney damage. Kidney impairment is a rare but serious side effect of Reclast.
It’s also best not to use Reclast if you’re also prescribed the medication Zometa. This is because they contain the same active ingredient — zoledronic acid. Combining them worsens the risk for side effects. And a similar rule applies to Prolia. Don’t use Prolia if you’re also prescribed Xgeva. Both contain the same active ingredient, denosumab.
Do Reclast or Prolia cause drug interactions?
Prolia doesn’t carry much risk for drug interactions. But Reclast has a few known interactions.
Using Reclast with medications that may lower your calcium levels can increase your risk of hypocalcemia. Examples include aminoglycosides such as gentamicin and loop diuretics such as furosemide (Lasix). If you need to combine these medications with Reclast, your rheumatologist may want to monitor your calcium levels more closely. They may adjust your medication doses, too.
Drugs that increase your risk of kidney damage, such as nonsteroidal anti-inflammatory drugs (NSAIDs), are also risky with Reclast. The combination can increase your risk of kidney damage and for this reason, are typically avoided with Reclast (when feasible).
If you have kidney damage and are receiving Reclast, medications such as digoxin (Lanoxin) may be slower to leave your body. This can lead to increased medication levels in your blood, which may cause added side effects.
It’s important for everyone on your healthcare team to know about all medications you’re taking to help prevent possible drug interactions.
Can you take Reclast and Prolia together?
No, Reclast and Prolia shouldn’t be taken together.
There’s limited information available about whether administering both together would make them more effective. But the combination is known to come with notable downsides. The risk of major side effects, such as hypocalcemia, ONJ, and atypical fractures, goes up by using both of these medications together.
Are there alternatives to Reclast and Prolia for osteoporosis?
Yes, several other medications can be used to treat or prevent osteoporosis. This includes:
Oral bisphosphonates: Common examples include ibandronate and alendronate (Fosamax).
Raloxifene (Evista): Raloxifene is an oral tablet that changes the way your body processes estrogen. It’s used to prevent or treat osteoporosis in women after menopause.
Calcitonin (Miacalcin): Calcitonin is another treatment option for osteoporosis. It’s typically prescribed for women with osteoporosis who are at least 5 years post-menopause and can’t take other medications for osteoporosis. It’s derived from salmon and can be given as a nasal spray or injection.
Teriparatide (Forteo) and abaloparatide (Tymlos): These injectable medications mimic the parathyroid hormone (PTH) that your body naturally makes. PTH helps manage calcium metabolism. Unlike other osteoporosis treatment options, these two medications focus on promoting new bone growth instead of limiting bone breakdown.
Romosozumab (Evenity): This newer osteoporosis injection helps your body build new bone and reduce breakdown of existing bone. It’s FDA approved for use in women who have gone through menopause that have a high risk of fractures. It can also be used as an alternative option for people who haven’t had luck with other osteoporosis medications.
How to save on Reclast and Prolia
Reclast and Prolia are both available as brand-name medications. But Reclast is also available as a lower-cost generic. GoodRx can help you navigate ways to save on your prescription.
Save with GoodRx. Generic Reclast’s price at certain pharmacies is as low as $62.41 with a free GoodRx discount.
Save with a copay savings card: If you have commercial insurance and meet eligibility requirements, Prolia’s price is as little as $25 per dose if you use the manufacturer’s savings card.
Save with patient assistance programs: If you’re uninsured or underinsured, you may be eligible for Reclast’s or Prolia’s patient assistance programs, which offer the medications at no charge.
Lower-cost biosimilars for Prolia are also approved for use. However, as of July 2024, they’re not commercially available in the U.S. yet.
The bottom line
Reclast (zoledronic acid) and Prolia (denosumab) are effective medications for treating osteoporosis and reducing the risk of bone fractures. These medications offer convenience with infrequent administration, too. Reclast is administered as an intravenous (IV) infusion once every year or two. Prolia is given under the skin every 6 months at your rheumatologist’s office.
They each come with some risks, though. Both Reclast and Prolia can lower your blood calcium levels. Calcium and vitamin D supplementation is usually recommended for anyone using these medications. Given their similarities and differences, it’s important to talk with your rheumatologist to help you decide if Reclast or Prolia is right for you.
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References
Amgen Inc. (2024). Prolia-denosumab injection [package insert]. DailyMed.
BluePoint Laboratories. (2024). ZOLEDRONIC ACID- zoledronic acid injection [package insert].
Choi, N., et al. (2017). Comparative safety and effectiveness of denosumab versus zoledronic acid in patients with osteoporosis: A cohort study. American Society for Bone and Mineral Research.
Novartis Pharmaceuticals Corporation. (2022). Reclast-zoledronic acid injection, solution [package insert].. DailyMed.
U.S. Food and Drug Administration. (2024). FDA approves first interchangeable biosimilars to Prolia and Xgeva to treat certain types of osteoporosis and prevent bone events in cancer.
U.S. Food and Drug Administration. (2018). FDA drug safety communication: New contraindication and updated warning of kidney impairment for Reclast (zoledronic acid).
U.S. Food and Drug Administration. (2024). Prolia (denosumab): Drug safety communication - FDA adds boxed warning for increased risk of severe hypocalcemia in patients with advanced chronic kidney disease.
