Bone Metastasis

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Systemic treatments for bone metastases

This section describes the types of systemic treatments used for cancers that have spread to bones. These treatments can reach cancer cells anywhere in the body.

Of course, cancers can also spread to other parts of the body. For more detailed information about treating a specific type of metastasis (such as breast cancer metastasis), please see our information on that type of cancer.

Some systemic treatments, such as chemotherapy, hormone therapy, targeted therapy, and immunotherapy, are used to treat cancer cells anywhere in the body. These treatments are not aimed specifically at bone metastases, but they often help treat them. Other systemic treatments, such as radiopharmaceuticals and bisphosphonates, are aimed more specifically at cancer that has reached the bones. Sometimes both of these types of treatments are used at the same time.

If you’d like more information on a drug used in your treatment or a specific drug mentioned in this section, see our Guide to Cancer Drugs , or call us with the names of the medicines you’re taking.


Chemotherapy (chemo) uses anti-cancer drugs that are usually injected into a vein or taken by mouth. These drugs enter the bloodstream and can reach cancer that has spread. Chemo is used as the main treatment for many types of metastatic cancer. Chemo can often shrink tumors, which can reduce pain and help you feel better, although it does not usually make them go away completely and stay away. It’s sometimes used with local treatments such as radiation.

Chemo drugs kill cancer cells but also damage some normal cells, which causes side effects. Side effects depend on the type of drugs, the amount taken, and the length of treatment. Some common chemo side effects include:

  • Nausea and vomiting
  • Loss of appetite
  • Loss of hair
  • Mouth sores
  • Diarrhea

Chemo can also damage the blood-producing cells of your bone marrow, which may lead to low blood cell counts. This can cause:

  • Increased chance of infection (caused by a shortage of white blood cells)
  • Problems with bleeding or bruising (caused by a shortage of blood platelets)
  • Feeling weak or tired (caused by low red blood cell counts, called anemia)

Most side effects go away once treatment is stopped. Things can be done to help prevent or control many of the side effects of chemo. For example, drugs can often prevent or reduce nausea and vomiting.

For more information about the chemo used for a certain type of cancer, see our document about that type of cancer (like Breast Cancer, Colorectal Cancer, Non-Small Cell Lung Cancer). To learn more about chemo in general, please see A Guide to Chemotherapy or go to the treatment section on our website

Hormone therapy

Hormones in the body drive the growth of some common cancers. For example, the female hormone estrogen promotes growth of some breast and uterus cancers. Likewise, male hormones (androgens such as testosterone) promote growth of most prostate cancers. One of the main ways to treat some of these cancers is to stop certain hormones from affecting the cancer cells. The main ways of doing this are lowering hormone levels and/or blocking the hormone’s action at the cancer cell.

One way to lower hormone levels is to surgically remove organs that make the hormones. For a woman with breast cancer, removing the ovaries lowers estrogen levels. Men with prostate cancer can be treated by removing the testicles to lower testosterone levels.

Another way which is used more often to lower hormone levels, is to give drugs to keep the hormones from being made. This is a common approach to hormone therapy for prostate cancer. Men can be given drugs such as luteinizing hormone-releasing hormone (LHRH) agonists or antagonists, which, in men, stop the testicles from making testosterone. The same drugs can be given to women to stop the ovaries from making estrogen.

Other drugs can be helpful in lowering hormone levels further in patients whose ovaries or testicles aren’t making hormones.

Another approach is to block the hormone’s action on the cancer cell. Drugs that do this include anti-androgens, selective estrogen receptor modulators, and anti-estrogens. For instance, tamoxifen blocks the effects of estrogen on breast cancers.

Side effects of hormone treatments depend on the type of treatment used. A common side effect for many of these treatments is hot flashes. Drugs that lower testosterone levels can lead to anemia, weight gain, loss of sex drive, breast development, weak bones, and other effects. Drugs that lower estrogen levels can lead to weak bones and body aches.

For more information about hormone treatment for a specific type of cancer, see our document about that cancer (like Breast Cancer or Prostate Cancer).

Targeted therapy

Although any drug used to treat cancer can be considered chemotherapy, drugs that work differently from traditional chemo drugs are often grouped separately. Some of these are called targeted therapy drugs. Targeted therapy drugs often go after the cancer cells’ inner workings – the programming that sets them apart from normal, healthy cells. These drugs tend to have different (and sometimes less severe) side effects from standard chemotherapy drugs. Targeted therapy drugs can be combined with other treatments, including chemo and hormone therapy. For some types of cancer, like kidney cancer, they are used alone as the main treatment for advanced disease.

For information about targeted therapy drugs used for a specific type of cancer, see our document about that type of cancer. General information about targeted therapy and its side effects can be found in our document Targeted Therapy.


Immunotherapy is a systemic therapy that boosts the body’s immune system or uses man-made versions of immune system proteins to kill cancer cells. Several types of immunotherapy are used to treat patients with metastatic cancer, including cytokines, monoclonal antibodies, and even a tumor vaccine. For more information about immunotherapy for a certain cancer, see our document about that cancer (such as Prostate Cancer, Melanoma Skin Cancer, or Kidney Cancer). More information about how immunotherapy works can be found in our document called Immunotherapy.


Radiopharmaceuticals are a group of drugs that have radioactive elements. These drugs are injected into a vein and settle in areas of bone with active turnover (like those containing cancer spread). Once there, the radiation they give off kills cancer cells.

If cancer has spread to many bones, radiopharmaceuticals work better than trying to aim external beam radiation at each affected bone. In some cases, radiopharmaceuticals may be combined with external beam radiation aimed at the most painful bone metastases (see “Radiation therapy” in the “Local treatments” section.)

Some of the radiopharmaceuticals approved for use in the United States include:

All of these have been shown to help with the pain caused by bone metastases. When given to patients with prostate cancer that has spread to the bones, radium-223 has also been shown to help patients live longer.

Treatment with a radiopharmaceutical can often reduce pain from bone metastases for several months. Re-treatment is possible when the pain returns, although the pain might not be reduced for as long as it was with the first treatment.

These drugs work best when the metastases are blastic, meaning the cancer has stimulated certain bone cells (osteoblasts) to form new areas of bone. Blastic metastases happen most often in prostate cancer that has spread to bone. They are found less often in breast cancers and are uncommon in most other cancers.

The major side effect of this treatment is lower blood cell counts (mainly white cells and platelets), which could put you at increased risk for infections or bleeding. This is more of a problem if your counts are already low before treatment. Another possible side effect is a so-called “flare reaction,” in which the pain gets worse for a short time before it gets better.

Radioactive iodine

Radioactive iodine (I-131) can also be considered a radiopharmaceutical. Unlike the other drugs discussed in this section, it does not concentrate in areas of bone with active turnover. It concentrates in thyroid tissue, and is used to treat thyroid cancer spread in bones and elsewhere in the body. This is discussed in more detail in our document, Thyroid Cancer.


Bisphosphonates (bis-FAHS-fun-ates) are a group of drugs that are useful in treating cancer that has spread to the bones. These drugs work by slowing down the action of bone cells called osteoclasts. These cells normally dissolve small bits of bones to help remodel them and keep them strong. But osteoclasts are often overactive when cancer spreads to the bones, which can cause problems.

Bisphosphonates can help with cancer that has spread to the bones by:

  • Reducing bone pain
  • Slowing down bone damage caused by the cancer
  • Reducing high blood calcium levels (hypercalcemia)
  • Lowering the risk of broken bones

Bisphosphonates tend to work better when x-rays show the metastatic cancer is thinning and weakening the bone (lytic metastases). They don’t work as well for treating blastic metastases, where the bones become denser.

Some bisphosphonates are taken by mouth, but most of those used as treatment for cancer are given by vein (IV), usually every 3 to 4 weeks. The most commonly used drugs are zoledronate (zoledronic acid or Zometa®) and pamidronate (Aredia®). People given these drugs are usually advised to take a supplement containing calcium and vitamin D to prevent problems with low calcium levels.

The most common side effects of bisphosphonates are fatigue, fever, nausea, vomiting, anemia (a low red blood cell count), and bone or joint pain. But other drugs or the cancer itself can cause many of these effects, too. These drugs can lower calcium levels, so they can’t be given to someone whose calcium levels are already low. Bisphosphonates can cause kidney damage and often cannot be given to people with poor kidney function.

A rare but very serious side effect of bisphosphonates is osteonecrosis (os-tee-o-nuh-CROW-sis) of the jaw (ONJ). In this condition, part of the jaw bone loses its blood supply and dies. This can lead to tooth loss and infections or open sores of the jaw bone that won’t heal and are hard to treat. ONJ sometimes seems to be triggered by having a tooth pulled while on a bisphosphonate. Many cancer doctors advise patients to get a dental check-up and have any tooth or jaw problems treated before they start taking a bisphosphonate. Maintaining good oral hygiene by flossing and brushing, making sure that dentures fit properly, and having regular dental check-ups might also help prevent ONJ.


Denosumab (Xgeva®, Prolia®) is another drug that can help when cancer spreads to bone. Like the bisphosphonates, this drug keeps osteoclasts from being turned on, but it does so in a different way, by blocking a substance called RANKL.

Studies have shown that it can help prevent or delay problems like fractures in patients with bone metastases at least as well as zoledronate. It also can be helpful when zoledronate is no longer working.

This drug is injected under the skin every 4 weeks. Patients given this drug may need to take a supplement containing calcium and vitamin D to prevent problems with low calcium levels.

Common side effects include nausea, diarrhea, and feeling weak or tired. Like the bisphosphonates, denosumab can cause osteonecrosis of the jaw (ONJ), so doctors recommend taking the same precautions (such as having tooth and jaw problems treated before starting the drug). Unlike the bisphosphonates, this drug is safe to give to patients with kidney problems.

Last Medical Review: 02/07/2014
Last Revised: 02/17/2014