What bisphosphonates are

Bisphosphonates are drugs used to slow down or prevent bone damage. They also lower calcium levels. You may hear them called bone hardening or bone strengthening treatment. Some cancers can cause bone pain and weakness. These are most often cancers that have started in another part of the body and have spread to the bone (secondary bone cancer). Some types of cancer treatment, such as chemotherapy and hormone therapies, can also weaken the bones.

The most common types of cancer that can affect your bones are

• Myeloma
• Secondary breast cancer
• Secondary prostate cancer
• Secondary lung cancer

Your doctors may prescribe bisphosphonates to

• Prevent or control bone thinning (osteoporosis)
• Reduce the risk of bones breaking
• Reduce the level of calcium in your blood
• Reduce pain

Bisphosphonate treatment can stop some types of cancer from spreading into the bone for some people. Studies have also shown that bisphosphonates can help some people with myeloma, secondary breast cancer, and secondary prostate cancer to live longer.

To understand how bisphosphonates work you first need to know a bit about normal bone activity, and how cancer can affect this. There is information below about

• Normal bone activity
• How cancer affects bones
• What bisphosphonates do

Normal bone activity

Your bones are made of living tissue, and are constantly changing. In healthy bones, specialised bone cells constantly break down and replace bone tissue. These specialised bone cells are

• Osteoclasts - which break down old bone
• Osteoblasts - which build new bone

This process is called bone remodelling and is very well controlled. There is a fine balance between the rates of bone breakdown and growth, which keeps bones strong and healthy.

How cancer affects bones

Myeloma and secondary bone cancers can spread into the bone, and damage it as they grow. Cancer cells that have spread to the bone also release proteins that interfere with the normal bone shaping process.

These proteins are

• Cytokines and
• Growth factors

These proteins stimulate the cells that break down bone (osteoclasts) and make them overactive. So bone is destroyed faster than it is rebuilt. This means your bones can become thinner and weaker, causing the following symptoms

• Pain in the affected bone
• High calcium levels in the blood
• Increased risk of breaks (fractures)

Calcium is normally stored in the bones and the breakdown of bone cells releases more calcium than usual into the blood. Doctors call a high level of calcium in the blood hypercalcaemia. Symptoms of hypercalcaemia include

• Feeling thirsty
• Constipation
• Feeling sick
• Feeling drowsy

There is detailed information about high calcium levels in our section about coping physically with cancer.

What bisphosphonates do

Bisphosphonates target the areas of higher bone turnover. The osteoclast cells absorb the bisphosphonate drug, which slows down their activity and reduces bone destruction.

There are several different types of bisphosphonates, and they each work slightly differently. Doctors are still learning more about the exact ways in which bisphosphonates work. We know that they can

• Interfere with the formation of osteoclasts
• Make osteoclasts self destruct, or die early
• Change the signalling between osteoclasts and osteoblasts
• Form a barrier between the bone and the osteoclast

Researchers have found that bisphosphonates can prevent or slow down the development of myeloma and secondary bone cancers in some people. Cancer cells appear to be attracted to an environment where bones are being broken down. Researchers hope that stopping this process could slow the growth of cancer and help people live longer, as well as reducing bone damage. There is more information about bisphosphonate research lower down this page.

There are several different types of bisphosphonates, including

• Disodium pamidronate (Aredia Dry Powder)
• Ibandronic acid or ibandronate (Bondronat)
• Sodium clodronate (Bonefos, Loron)
• Zoledronic acid or zoledronate (Zometa)

You can have clodronate (Bonefos, Loron) and ibandronate (Bondronat) either as a tablet or by drip into your vein (infusion). You have zoledronic acid (Zometa) and pamidronate (Aredia) as a drip. You can find out more about having these drugs, and their particular side effects, by using the links above for each drug.

Most of the research so far has looked at using bisphosphonates with secondary breast cancer, secondary prostate cancer and myeloma. The type of bisphosphonate your doctor prescribes for you will depend on the type of cancer you have. You will have one that works for your type of cancer.

It may not always be possible for the doctor to say if one bisphosphonate is better than another for your cancer. So far there have been few studies comparing different types of bisphosphonates, but this is an area of active research. Your doctor will give you the bisphosphonate best suited to your medical and practical needs. For example, you might prefer to take a bisphosphonate tablet at home rather than travel to hospital every month and have treatment by drip.

Researchers are testing several bisphosphonate drugs in clinical trials for different cancers. These include trials testing zoledronic acid (Zometa) in men with prostate cancer. And trials are comparing radiotherapy with ibandronate as a way of relieving pain caused by secondary bone cancer in people with breast, prostate or lung cancer. The ZICE trial is comparing zoledronic acid with ibandronate for breast cancer that has spread to the bones.

Several studies show that zoledronic acid may prevent bone loss in pre menopausal women having treatment for early breast cancer. Other studies are looking at the timing of giving bisphosphonates to people having chemotherapy. Research seems to show that bisphosphonates can make cancer cells more sensitive to chemotherapy. So, small studies are looking at giving the bisphosphonate zoledronic acid by drip just before doxorubicin chemotherapy. The ANZAC trial is looking at whether giving women with breast cancer FEC chemotherapy just before zoledronic acid works better than FEC chemotherapy on its own.

Newer types of treatment which also work on the bones, such as the monoclonal antibody denosumab, are being used in clinical trials for various types of cancer.

You can find out more about current clinical trials using bisphosphonate drugs on our clinical trials database by searching under your specific cancer type.