Healthcare providers prescribe bisphosphonates to help treat osteoporosis and other conditions that affect the density and strength of your bones. There are oral and IV bisphosphonates. Common side effects include gastrointestinal issues, like reflux and esophagus inflammation.


What are bisphosphonates?

Bisphosphonates are a class of medications that help treat osteoporosis. Healthcare providers also prescribe them for other conditions that affect the density and strength of your bones and for some conditions that cause very high blood calcium (hypercalcemia).

Osteoporosis is a condition that weakens your bones. It increases your risk for sudden and unexpected bone fractures. Osteoporosis means that you have less bone mass and less bone strength.

What are the types of bisphosphonates?

There are two main types of bisphosphonates — oral (taken by mouth) bisphosphonates and IV (intravenous, or through your vein) bisphosphonates.

Oral bisphosphonates that healthcare providers in the United States can currently prescribe include:

IV bisphosphonates that providers can currently prescribe in the U.S. include:


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What conditions do bisphosphonates treat?

The United States Food and Drug Administration (FDA) has approved bisphosphonates to treat the following conditions:

Healthcare providers sometimes prescribe bisphosphonates for other conditions. This is an off-label, or non-FDA-approved, use of the medication. Off-label uses include:

  • The treatment of osteogenesis imperfecta in children and adults.
  • The prevention of glucocorticoid-induced osteoporosis.
  • Fracture prevention in children and adults — due to having multiple risk factors for fracture such as chronic illnesses — and organ transplant candidates.

Procedure Details

How do bisphosphonates work?

Your bones constantly renew themselves. This is a natural process. Your body breaks down older bone and removes (resorbs) it. Then new bone forms. As you age, your bone density tends to decrease because your body breaks down bone faster than new bone forms.

Bisphosphonates work by slowing down bone resorption (removal). They help strengthen your bones and prevent future bone fractures.


How do you take bisphosphonates?

You may take oral bisphosphonates either daily, weekly or monthly, depending on the specific medication and the reason for taking it. You usually have to take these medications first thing in the morning on an empty stomach with water. You also have to remain upright (sitting or standing) for 30 to 60 minutes after taking the medication and shouldn’t eat or drink anything during this time.

In any case, your healthcare provider will give you specific instructions for taking the medication. Be sure to follow them.

You receive IV bisphosphonates as an infusion through a vein in your arm at your provider’s office or an infusion center — usually once a year, but sometimes more often, depending on why your provider prescribed the drug.

Your provider will likely recommend that you:

  • Eat a calcium-rich diet.
  • Take a vitamin D supplement if you have vitamin D deficiency.
  • Take a calcium supplement if you’re unable to eat enough calcium.

How long will I need to take bisphosphonates?

You and your healthcare provider will discuss how long you should take a bisphosphonate depending on your specific situation.

Most providers limit treatment with oral bisphosphonates to five years (or three years for IV zoledronic acid) to minimize the risks of rare side effects. However, some people may need longer treatment.

Risks / Benefits

What are the side effects of bisphosphonates?

Each type of bisphosphonate has different possible side effects. It’s important to talk to your provider or a pharmacist about possible side effects of the specific medication you’re taking.

In general, a relatively common side effect of oral bisphosphonates is upper gastrointestinal (GI) issues, including:

IV bisphosphonates may cause a reaction of flu-like symptoms, such as:

  • Fever.
  • Achiness.
  • Mild headache.
  • Bone, joint and muscle pain.

If these side effects occur, they typically do so within one to three days of the infusion. The symptoms usually respond to acetaminophen or NSAIDs and resolve within a few days.

Other possible side effects of bisphosphonates, which are extraordinarily rare, include:


Are bisphosphonates effective?

All bisphosphonates improve bone density. Studies show that certain types of bisphosphonates decrease the risk of various types of bone fractures. For example:

  • Alendronate reduces vertebral (spine) fracture risk by about 50%. It reduces the risk of hip fractures and other nonvertebral (non-spine) fractures by about 30%.
  • Risedronate reduces the risk of vertebral and nonvertebral fractures by about 40%.
  • Zoledronic acid reduces vertebral fracture risk by about 70%. It reduces the risk of hip fractures and other nonvertebral fractures by about 35%.
  • Ibandronate reduces the risk of vertebral fractures by about 50%.

When To Call the Doctor

When should I see my healthcare provider?

You should have regular appointments with your healthcare provider when taking a bisphosphonate to assess how well it’s working and any bothersome side effects.

You should also follow up with a bone specialist such as an endocrinologist or rheumatologist to monitor the health and strength of your bones. They may recommend getting a bone density test (DXA) in order to measure and track the changes in your bone mineral.

Long-term use of bisphosphonates can increase the risk of atypical femur fractures, particularly in at-risk populations. Again, this is rare, but if you’ve been taking a bisphosphonate for at least three years and you develop pain in your thigh or groin, contact your provider’s office.

A note from Cleveland Clinic

Bisphosphonates are prescription medications that help treat osteoporosis and other bone conditions. You may have concerns about taking bisphosphonates due to the risk for side effects. Know that the risks of taking bisphosphonates pale in comparison to the risk of sustaining what could be a life-changing osteoporotic fracture. Don’t be afraid to ask your healthcare provider questions or tell them about your concerns. They’re available to help.

Medically Reviewed

Last reviewed on 02/21/2023.

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