Bisphosphonates

What are bisphosphonates?

Bisphosphonates are drugs that in certain situations can help to protect your bones against some of the effects of cancer, such as pain and weakness. They may also be used to reduce a raised calcium level in the blood.

They are also used in the treatment of conditions other than cancer, such as osteoporosis. This information is about their use in cancer.

When they may be used

Bisphosphonates are usually given alongside other cancer treatments. They have been shown to be effective in people with myeloma (a cancer of the plasma cells of the blood) and people who have secondary bone cancer. Secondary bone cancer occurs when the original cancer (the ‘primary’) spreads to form a secondary cancer (metastasis) in the bone.

Bisphosphonates are often used to treat people with advanced breast or advanced prostate cancer, as these cancers can often spread to the bones. They are also sometimes used for other types of cancer that have spread to the bones.

Effects of cancer on the bones

In secondary bone cancer, calcium (which helps to strengthen the bones) can be lost from the damaged bone and can seep into the bloodstream. When the level of calcium in the blood is raised this is known as hypercalcaemia and can cause symptoms such as nausea, vomiting, tiredness, irritability and sometimes confusion. Bisphosphonates can help to reduce high levels of calcium.

Secondary cancer in the bones may cause them to become weakened, and in some situations they may break or fracture. Bisphosphonates can help to re-strengthen the bone and reduce the risk of fractures.

Cancer can affect the bones in different ways, and bisphosphonates are not helpful for all cancers that affect the bones.

How they work

In normal bone two types of cell (osteoclasts and osteoblasts) work together constantly to shape, rebuild and strengthen existing bone:

• osteoclasts destroy old bone
• osteoblasts build new bone

Myeloma and some secondary bone cancers can produce chemicals that make the osteoclasts work harder. This means that more bone is destroyed than rebuilt, and leads to weakening of the affected bone. This can cause pain and means that the bone can fracture or break more easily.

Bisphosphonates target areas of bone where the osteoclast activity is high. They help to re-establish the normal balance of osteoclast and osteoblast activity. This can reduce pain and help to strengthen the bone. It also means that less calcium will be lost from the bones. Bisphosponates do not affect normal bone.

How they are given

Bisphosphonates can be given in two ways.

• Intravenously  As a drip (infusion) into the vein, through a fine tube called a cannula. The infusion may take from 15 minutes to 3 hours depending on which bisphosphonate is being given.
• As tablets  Usually taken either once or twice a day. It is recommended that you take the tablets in the morning and evening and
  not within 1–2 hours of eating or taking a milky drink or other medicines. Your nurse or doctor will explain how you should take your tablets.

Names of bisphosphonates

The main bisphophonates used to treat people with cancer are:

• disodium pamidronate (Aredia Dry Powder®)
• ibandronic acid (Bondronat®)
• sodium clodronate (Bonefos®, Loron®)
• zoledronic acid (Zometa®)

Possible side effects

Bisphosphonates do not generally cause many side effects. However, some people may have the effects described below to varying degrees:

The side effects that may occur with either the tablets or the infusion are discussed first. Side effects that only occur with the tablets are then listed and lastly those that only occur with the infusion.

Possible side effects of the tablets and of an infusion

• Drop in calcium levels below normal  This is extremely rare and usually only temporary.
• Change in kidney function  Rarely, bisphosphonates can affect the function of the kidneys. This does not usually cause any symptoms and the effect is usually mild. Your doctor will monitor how well your kidneys are working during your treatment by doing a blood test.
• Increased pain  Sometimes pain in the affected bone can temporarily become worse when you first take bisphosphonates. If this happens your doctor can prescribe stronger pain-relieving drugs for you until this side effect wears off.

Possible side effects of the tablets

• Feeling sick (nausea) or vomiting  Nausea and vomiting is usually mild and can be well controlled with anti-sickness medication.
• Abdominal pain and diarrhoea  Rarely, bisphosphonates can cause diarrhoea.

It is important to tell your doctor if these effects develop, as medicines can be prescribed to help. Sometimes taking half the dose of the drug in the morning and half in the evening can reduce the side effects. Occasionally the dose of the bisphosphonate may need to be reduced. Your doctor will advise you whether this is necessary.

Possible side effects of the intravenous infusion

These are rare and may include a high temperature and chills, a headache, confusion and aching joints and muscles.

How long they are given for

Bisphosphonates to lower calcium levels are usually given into the vein (intravenously). This may be a single dose or as a short course over a few days. Tablets or capsules can then be given to maintain your calcium at a normal level. It is usually possible to have this treatment as an outpatient.

If you are having bisphosphonates to reduce pain, or strengthen your bones, then you may need to take them as long as they seem to be working for you. They may be given as an intravenous injection every 3–4 weeks or as tablets taken daily.

Additional information

If you need to see your dentist for any treatment, such as having a tooth removed, it is important to let them know that you are taking bisphosphonates. Rarely bisphosphonates can cause problems of infection and delayed healing following dental surgery.

Current research is looking at whether bisphosphonates might be helpful in treating the symptoms of other types of cancer that have spread to the bones. Research is also being carried out to see whether bisphosphonates can help to slow the growth of the cancer.

References

This section has been compiled using information from a number of reliable sources including:

• Martindale: The Complete Drug Reference (33rd edition). Sweetman et al. Pharmaceutical Press, 2002.
• British National Formulary (48th edition). British Medical Association and Royal Pharmaceutical Society of Great Britain, September 2004.
• Palliative Care Formulary (2nd edition). Twycross et al. Radcliffe Medical Press, 2002.

For further references, please see the general bibliography.