How do cancer cells effect the bones?

It is possible in some patients for cancer cells to spread from its original site to the bones. For example, the breast and prostate. They then grow into small tumours which release chemicals which upset the normal balance between bone formation (osteoblast cells) It is possible in some patients for cancer cells to spread from its original site, for example the breast, to the bones. They then grow into small tumours which release chemicals which upset the normal balance between bone formation (osteoblast cells)  and bone reabsorption (osteoclast cells).
These chemicals stimulate osteoclasts to excessively reabsorb bone, release of calcium into the blood stream, reduced bone density, leading to holes in the bones and weakness. Weak bones lead to bone pain and fracture. A high calcium (Hypercalcaemia) can cause a number of troublesome symptoms including;

• Dry mouth, thirst & dehydration due to passing of excessive urine.
• Constipation.
• Nausea & vomiting.
• Severe tiredness, muscle weakness.
• Low mood leading to depression.

Who should take bisphosphonates?   
Mainly patients who have a cancer which has spread to the bones. Most often this is patients with breast cancer but it is sometimes recommended for patient with other types of cancer including prostate, lung and myeloma. It is most often given to patients where the cancer in the bone has caused pain or signs of weakness.  It is particularly recommended if the level of calcium in the blood stream is raised. There is some good evidence that giving bisphosphonates to patients as soon as they develop boney disease prevents the progression of  pain or weakness in the bones.

How are bisphosphonates taken?   
They can be given by mouth every day or into a vein once every 3-4 weeks. Usually if the calcium is raised in the blood stream bisphosphonates are given as an infusion into a vein (intravenously), followed either by regular injection thereafter or regular oral medication. Evidence has shown that it is best to continue bisphosphonates regularly if a patient has had an episode of hypercalcaemia as without it the calcium will slowly rise again leading to troublesome symptoms (see above). 

Three commonly used oral drugs in the UK are:- 

• Loron
• Aredia
• Bonefos
• Ibandronate

When taken by mouth, two tablets are usually taken per day.  They can be taken at the same once a day or one tablet taken twice per day. They should be taken at least 1 hour before or 1 hour after a meal. The tablets should be swallowed with a drink not containing milk as calcium reduces the absorption of the tablets. It is also important to avoid iron, mineral supplements or ant-acids for indigestion and to maintain adequate fluid intake. Occasional patients are asked to take four tablets a day.

Side effects 
These drugs taken orally are generally well tolerated but occasional side effects can occur. Mild symptoms are usually in the form of tummy upset:-

• mild nausea
• mild indigestion
• mild diarrhoea

If these develop it is recommended that the dose of the tablets are reduced by half for a few days and then gradually increased back to two tablets a day but taken separately. A slight change in the diet may also be required See "diet & diarrhoea", and diet & indigestion.   If someone has a history of inflammatory bowel disease they should not take oral bisphosphonates unless under strict supervision, in this situation it may well be better to take the intravenous route. Other rare side effects are possible and are listed below. As with all medications it is also possible to have side effects not expect or listed below, If an unusual symptom or side effect appears let your doctor know:-

• Occasionally patients may experience mild itching and very rarely a rash.
• Occasionally the level of calcium in the blood stream may drop but patients are monitored for this with blood tests. Very rarely would a patient notice a low level of calcium in their symptoms.

Taken intravenously bisphosphonates are generally well tolerated but occasional side effects can occur. These are mentioned below but it is rarely possible to develop side effects not mentioned here. If in doubt ask!

• Mild flu like symptom, aching muscles and joints, headache, malaise, rigors & nausea.
• Mild itching and occasional skin rash.
• Occasional mild ankle swelling

These symptoms are caused by a mild allergic reaction. They can usually be corrected next time by a small dose of intravenous steroids (e.g. Dexamethasone 4mg iv).
For both Intravenous and oral medication,  patients who have moderate to severe renal failure should only take Bisphosphonates only under strict supervision. Care should be taken with non-steroidal anti-inflammatory drugs.

Other issues with bisphosphonates

Bisphosphonate prescribing; eg Risedronate 35mg or Aledronate 70mg PO once weekly. Always prescribe a calcium/vitamin D supplement such as Adacal-D

Weekly bisphosphonate dosing is effective, better tolerated than daily (avoids daily insult to oesophagus) with better compliance.

Dosing instructions are critical and should be reinforced at follow-up visit: take first thing in the morning, follow by drink of water, sit upright for 30 minutes, do not take lying down and do not eat or drink for 30 minutes after taking the tablet.

DEXA response to bisphosphonates is virtually universal (failure of response is a sign of non-compliance), so no need to rescan until end of five year course (more valuable to spend time ensuring compliance at each follow up visit).

Bisphosphonates are absolutely contraindicated in pregnancy so make sure younger patients are aware of this and taking appropriate precautions, even if apparently menopausal. A 6 month washout period is needed after risedronate if attempting to conceive (which is the same as the recommended tamoxifen washout period).

Patients who cannot tolerate oral bisphosphonates and have T scores less than -2.5 should be given monthly pamidronate infusions for five years.  Other intravenous preparations as they become licensed may become preferable.

Patients who have moderate to severe renal failure should only take Bonefos only under strict supervision. Care should be taken with Bonefos if it is taken with non-steroidal anti-inflammatory drugs.

Patients who have moderate to severe renal failure should only take Bonefos only under strict supervision. Care should be taken with Bonefos if it is taken with non-steroidal anti-inflammatory drugs.

Further information