Bisphosphonate treatment for children

Bisphosphonates are a type of medicine. They are used to strengthen bones and reduce the risk of further fractures. Bisphosphonates can also help reduce pain caused by some bone conditions. Sometimes we give bisphosphonates before spinal and orthopaedic surgery, as they can help improve outcomes.

There are three main bone cells:

• Osteoblasts make new bone.
• Osteoclasts remove old bone to make room for new bone.
• Osteocytes control the action of osteoblasts and osteoclasts.

The normal continuous cycle of removing old bone and making new bone (remodelling) keeps bones strong.

Bisphosphonates ‘stick’ to bone to slow down the activity of the osteoclasts, while the osteoblasts continue to add new bone during growth.

The two main bisphosphonates we use are zoledronate (zoledronic acid) and pamidronate. Both medicines are given as an intravenous infusion (through a vein).

Your team will decide which medicine to use. We consider the condition being treated, your child’s age, and best practice.

Bisphosphonates are given through intravenous infusion. This is through a cannula – a small plastic tube – or a Central Venous Access Device (CVAD) if your child has one.

Before inserting the cannula, the doctor or nurse will apply a numbing cream or cold spray to make the area more comfortable. They will then insert the canula into your child’s arm or the back of their hand.

The cannula or CVAD can then be used to take blood and to give the medication.

The two medicines are given slightly differently:

Pamidronate is given as an infusion over four to six hours, once a day for three days. In infants, it may be given more slowly over six to eight hours. Your child will usually stay in hospital overnight during this time.

The treatment course is repeated every six to eight or 12 weeks depending on the age of your child.

Zoledronate is given as an infusion over 30 to 45 minutes. Your child will usually stay in hospital overnight for their first, and sometimes their second, infusion. Future infusions are usually given as a day admission.

The treatment course is either repeated every three months for the first three infusions and then given every six months, or every four to six months from the start. This could be different (and needed more frequently) depending on the age of your child.

We want your child to feel safe and comfortable during their admission. We understand that some children, for example those who are neurodiverse and/or find hospital visits stressful, may need additional support.

We have Play Specialists who can support children to feel less stressed and more prepared for their procedure, through therapeutic play. Please let us know if you would like your child to meet with a Play Specialist.

Please make sure that your child is well hydrated and has eaten before admission. They can eat and drink normally during the treatment and should be encouraged to drink plenty of water.

We will do a blood test before each infusion to check important things such as calcium and vitamin D levels, and kidney function. The test results must be normal before we can give your child an infusion.

The nurses will check your child’s pulse and temperature. We are careful when measuring blood pressure because of the risk of fractures and will only do this if necessary.

• You might notice an improvement in bone pain after one or two infusions.
• We will check for improvements in the vertebrae (bones of the spine) and bone mineral density once a year by taking an X-ray and DXA scan.
• We will listen to you and your child’s feedback on symptoms, such as fatigue, pain, and fractures.

Flu-like symptoms

It is common for children to feel unwell for a few days after the first infusion. These side effects are expected, and include:

• High temperature
• Shivers
• Tiredness
• Upset stomach
• Nausea and vomiting
• Aches, pains, and stiffness in muscles and joints (this can last up to two weeks).

These side effects are usually easily managed at home with over-the-counter pain relief such as paracetamol.

Hypocalcaemia (low calcium level)

This does not usually cause you to feel unwell, however, symptoms of a low calcium level include:

• Muscle cramps
• Tingling, numbness, or aching around the mouth, fingers, or feet
• Fatigue
• Seizures (rarely)

To prevent hypocalcaemia, we recommend a good amount of calcium in the diet. Calcium supplements may be recommended a week before and after the infusion, or for just five to seven days after the infusion to make sure your child has enough calcium.

Calcium can be prescribed as:

• A tablet – some are chewable or can be crushed into food.
• An effervescent tablet or sachet of granules that can be dissolved in a small amount of water.

Please let us know what form of calcium your child might prefer.

It is important that your child also takes a vitamin D supplement, as it is needed for calcium absorption. If the vitamin D level is too low, then the bisphosphonate cannot be given. We recommend that children on bisphosphonates over 12 months have 400 to 1000 units of vitamin D daily. Vitamin D is available over the counter in different preparations. Please speak with your pharmacist for further information.

• Read advice from the British Dietetic Association (BDA) on a calcium rich diet.
• Advice from the BDA on vitamin D.

All children on regular steroids should start steroid ‘sick day’ doses at the start of their infusion and for the next three days. This is the same dose as in your child’s illness care plan.

Side effects are less likely with future infusions, but some children continue to have side effects after each infusion. If your child has had more significant or prolonged side effects, we recommend continuing routine steroid sick day doses with every infusion.

It is usual practice to leave a gap between an infusion and some types of surgery. This includes osteotomy – when a bone is cut – and posterior spinal fusion – used to correct scoliosis.

Infusions will be stopped two to four weeks before surgery. Infusions will be restarted after surgery when healing is seen on an X-ray.

Please let us know of any planned surgery (including dental surgery) so we can re-arrange the infusion dates, if needed.

Bisphosphonates do not affect healing after a broken bone.

If your child is unwell – for example with a fever or infection – then the infusion may need to be cancelled.

If your child is unwell in the two weeks before an infusion, please let us know.

Osteonecrosis of the jaw

This is a condition where the blood supply to the jawbone is blocked, causing weakness and damage to the bone, and pain. Adult patients on long-term bisphosphonate treatment are at increased risk of having osteonecrosis of the jaw. This condition has not been reported in children. We recommend that all children have good oral hygiene and get a dental check-up every six months. Let your dentist know that your child is on bisphosphonates. Let us know if your child is having dental surgery, and we might recommend rearranging their infusion date.

Bisphosphonates and pregnancy

There is no evidence that unborn babies are affected by bisphosphonates. However, we strongly advise that sexually active girls on bisphosphonates use contraception and stop treatment if they become pregnant.

Iritis

Inflammation of the eye (called iritis) can cause eye redness, pain, and change in vision. This has been reported in people on bisphosphonates, but it is very rare.

Atypical fractures

Atypical fractures are unexpected fractures usually in the femur (thigh bone). These have been seen in adults on long-term bisphosphonate treatment but not reported in children.

There is a tablet type of bisphosphonate which is given once a week. This treatment is recommended in only a small number of children and young people because it does not work as well as the IV medicines and can irritate the oesophagus (food pipe). We would only consider this form of treatment if we were unable to give your child IV medicine.

This depends on the condition being treated and whether it is shown to be of benefit. Your team will discuss this with you in more detail.

• For parents of children with OI (Osteogenesis Imperfecta) please message us through My GOSH at: GOSH Neurodisability CNS (Osteogenesis Imperfecta)
• For parents of children under the care of the Metabolic Bone Disease Service, please message us through My GOSH at: GOSH Endocrine Calcium Bone Team.

• Royal Osteoporosis Society – Osteoporosis in Children
• Brittle bone society