Bone-Modifying Drugs for Breast Cancer

February 22, 2011

To help doctors give their patients the best possible care, the American Society of Clinical Oncology (ASCO) developed evidence-based recommendations for using drugs, called bone-modifying drugs, for advanced breast cancer that has spread to the bone to help prevent bone-related problems. In 2011, this guideline was updated based on results from clinical trials of these drugs, including new information about a possible condition experienced by some people taking bone-modifying drugs. It also includes a new drug, denosumab (Xgeva), which was approved by the U.S. Food and Drug Administration (FDA). This guide for patients is based on ASCO's most recent recommendations.

Key Messages

  • Bone-modifying drugs are used to help to prevent bone problems for people with breast cancer that has spread to the bones.
  • The bone-modifying drugs used in the United States for breast cancer that has spread to the bone are pamidronate (Aredia), zoledronic acid (Zometa), and denosumab; talk with your doctor about the benefits and risks of each drug.
  • Bone-modifying drugs are associated with an uncommon but possibly serious side effect called osteonecrosis of the jaw.


In the United States, breast cancer is the most common cancer in women (excluding skin cancer) and the second most common cause of death from cancer in women. Breast cancer in men is much less common, accounting for less than 1% of all breast cancer diagnoses. Sometimes, breast cancer spreads outside of the breast in a process called metastasis. One of the most common distant places breast cancer can spread is the bone. When breast cancer has spread to the bone, people may experience significant pain and loss of movement. To manage these problems, your doctor may use medications, surgery, or radiation therapy.

Bone-modifying drugs are used to help strengthen the bone and reduce pain and fractures (bone breaks) from bone metastases. These drugs can also lessen the need for surgery or radiation therapy to manage bone problems, so they are often used for patients with bone metastases from breast cancer. However, these drugs have not been shown to extend life or slow the growth of breast cancer. There are two different classes of bone-modifying drugs and both help stop the bone from breaking down. One class, called bisphosphonates, is used for bone metastases and includes pamidronate and zoledronic acid. The drug denosumab is an antibody made in a laboratory that also helps stop bone breakdown.

A possible condition associated with bone-modifying drugs is osteonecrosis of the jaw. It is an uncommon but serious condition. The symptoms of osteonecrosis of the jaw include pain, swelling, and infection of the jaw; loose teeth; and exposed bone.

The side effects of pamidronate and zoledronic acid include flu-like symptoms that may occur with the first few doses and kidney problems. It's important for your health care team to do blood tests to check your kidney function before each dose. Denosumab is not specifically associated with kidney problems, but can cause hypocalcemia (low levels of calcium in the blood). Your doctor may recommend calcium and vitamin D supplements to reduce the risk of hypocalcemia if you are taking any bone-modifying drug for breast cancer that has spread to the bone. The dose and how often you should take calcium and vitamin D supplements is different for each person and should be discussed with your doctor.


ASCO recommends the following for the use of bone-modifying drugs for breast cancer:

  • Bone-modifying drugs are recommended for people with breast cancer who have evidence of bone metastases on an x-ray. They are also recommended for people with evidence of bone metastases on a bone scan and a computed tomography (CT) scan or magnetic resonance imaging (MRI), even if an x-ray shows no evidence. Results of a bone scan alone should not be used to recommend treatment.
  • If you are taking one of these drugs, talk with your doctor about how long you should take the drug since doctors often recommend that patients keep taking the drug because the risk of having bone problems continues.
  • If you have breast cancer that has spread to the bone, you should talk with your doctor about choosing a bone-modifying drug. The choice of drugs depends on your overall health, your individual risk of side effects, the cost, and the amount of time needed for each dose. For example, pamidronate is given intravenously (IV; through a vein) every three to four weeks for at least two hours. Zoledronic acid is given by IV every three to four weeks for at least 15 minutes. Denosumab is given as an injection under the skin (called a subcutaneous injection) every four weeks.
  • If you are taking pamidronate or zoledronic acid, you should have a blood test for creatinine levels each time the drugs are given. Creatinine is a type of protein in the blood that shows how well the kidneys are working. High levels of creatinine may indicate kidney damage and that the medications you are taking may need to be changed. Calcium, electrolytes, phosphate, magnesium, and hematocrit/hemoglobin should also be monitored regularly. If you are receiving denosumab, you should be tested for creatinine levels before the first dose and monitored for hypocalcemia. Talk with your doctor about when and how often these should be monitored.
  • Before taking bone-modifying drugs, you should have a thorough dental examination, and any invasive procedures to the jaw bone or treatments for mouth infections should be done before starting these drugs. While receiving bone-modifying drugs, you should take good care of your teeth, mouth, and gums and avoid having any unnecessary invasive dental work done, such as dental surgery. Following these recommendations may help lower the risk of osteonecrosis of the jaw.
  • Although bone-modifying drugs may help reduce or lessen pain over the long term, they should not replace other treatments to reduce pain. Patients who experience bone pain should receive other medications and/or radiation therapy and/or surgery that are commonly used to manage the pain.

Research on bone-modifying drugs is ongoing. At this time, people with breast cancer in the situations listed below should take bone-modifying drugs only as part of a clinical trial:

  • Patients with breast cancer who have evidence of bone metastases only on a bone scan, but not on x-ray, CT scan, or MRI
  • Patients who have breast cancer that has spread to other parts of the body but have no evidence of bone metastases

Bone-modifying drugs help strengthen bones and are an important part of treatment for patients with breast cancer that has spread to the bones. The bone-modifying drugs used in the United States to treat bone metastases are pamidronate, zoledronic acid, and denosumab. Talk with your doctor about the differences between these drugs, including the cost, and the type of preventive care, such as dental care, that you'll need before taking a bone-modifying drug. It's also important to discuss the tests you'll need to monitor your health while taking a bone-modifying drug, as well as other ways to improve bone health.

Questions to Ask the Doctor

  • Has the breast cancer spread to my bones?
  • What are options for treating the pain I'm having from the cancer that has spread to my bones?
  • Do you recommend bone-modifying drug treatment? If so, which drug do you recommend and why?
  • What tests and procedures do I need before starting a bone-modifying drug?
  • How long do I need to take this drug?
  • How will the drug be given?
  • What side effects can I expect from this treatment?
  • What is the risk of developing osteonecrosis of the jaw? What signs or symptoms should I watch for?
  • What other signs or symptoms should I look for?
  • How will my treatment be monitored?
  • What clinical trials are open to me?
  • Where can I find more information?

Helpful Links

Read the entire clinical practice guideline at

Guide to Breast Cancer

ASCO Answers Fact Sheet: Breast Cancer

Dental Health During Cancer Treatment

Bone Health During Cancer Treatment