Hope for children with brittle bones
Reproduced from Issue 107 of Arthritis Today
There is a small group of children whose bones are as thin and brittle as cardboard and which break if they cough or sneeze – who have to be carried around on pillows by their parents for their own protection. But now, thanks to pioneering work in Sheffield, they now have hope…
AROUND 200 youngsters in the UK are severely affected by a rare, inherited form of osteoporosis called osteogenesis imperfecta. Until recently, very little could be done for them, and they were likely to end up in wheelchairs by the time they were teenagers, their growth stunted, and their bodies deformed.
However, many of these children are due to take part in national clinical trials of an exciting new drug treatment led by Nick Bishop, Professor of Paediatric Bone Disease, an internationally renowned expert on the treatment of brittle-bone disease in children.
Funded by a three-year £238,000 Senior Research Fellowship from the Arthritis Research Campaign, Professor Bishop, who is based at Sheffield Children's Hospital, is testing the effectiveness of a new group of drugs only recently used on children with osteoporosis, called bisphosphonates. And already the results are astonishing.
"No-one anticipated how dramatic the effects would be in this group of children," says Professor Bishop. "It's almost too good to be true. Unless you have seen it happening in front of you own eyes you would not believe it."
He found that the children taking bisphosphonates experience an increase in their bone density of 40 per cent a year – compared to normal children whose bone density growth is just ten per cent. In the most severe cases the youngsters' bone density doubled. It also reduced their chronic pain, and the number of fractures.
It has another knock-on benefit too. "Children who are invalids will lose bone mass if they are immobilised for whatever reason, which can cause bone to fracture spontaneously without any trauma whatsoever," adds Professor Bishop:
"Because the children on bisphosphonates feel so much better, they can do more exercise and put more stress on their bones. In fact, their parents are often quite worried that they are going to do too much, which will lead to them breaking bones."
The effects on one little girl, two-year-old Holly Girven, from Sheffield, are typical. Just one month after starting the new drug treatment, Holly is crawling and attempting to walk. Before, she could only roll about and was very cautious in her movements. Mum Lynne says: "She is like a new little girl. The difference is just incredible."
Although the bones of youngsters with OI will become stronger as they continue to take the drugs, they will never be as strong as other children's, nor will their lives ever be "normal". Nevertheless, Professor Bishop believes the drugs are a major advance and can transform their quality of life.
"Can you imagine being a teenager and not having the strength to get out of your wheelchair to get to the loo, or being helped in and out of bed every night? With a younger child that's OK but if you are a teenager it could make you suicidal. These are very determined, sparky group of youngsters."
It was while he was working with a leading Canadian doctor in Montreal, who pioneered the use of bisphosphonates in children, that Nick Bishop became aware of their enormous potential in slowing down bone loss and actually rebuilding bone.
On his return to Britain he decided to set up the first-ever clinical trial of the drugs using three groups of affected youngsters. Already the first group is undergoing treatment, and studies of the second group which will involve young infants are due to start by the end of this year. The third group of 60 youngsters who will be trying out a new bisphosphonate, is awaiting further funding.
Nick Bishop hopes the drugs will soon be available in medicine form, so that youngsters don't have to keep coming back into hospital to be hooked onto an intravenous drip for three days, which most of them hate.
Bisphosphonates have been used in the treatment of adult osteoporosis for 20 years. But doctors were afraid to use them on children. "The reasoning was that if you slow down the bone turnover you might impair growth and cause rickets, and impair the fracture healing process," explains Nick Bishop. "But these fears appear to be completely unjustified."
OI is an inherited form of osteoporosis, due to a mutation in the type one collagen gene, affecting around 2,000 children in the UK in varying degrees of severity.
In the long term, children with OI will continue to take the drugs into their teens and early adult life. Once their bone density reaches a near normal level and stop fracturing, they may be able to come off the drugs. "If they stop fracturing and they have no deformity, they may be able to have a normal quality of life. We don't know if that will happen, but we hope it does," he adds.
Case study
EVER since she was born with severe osteogenesis imperfecta, 11-year-old Leah Rednall from Cambridge has suffered regular fractures because of her thin bones, and undergone numerous operations to straighten her arms and legs.
But since she started coming up to Sheffield for her four-monthly treatment of intravenous bisphosophonate, her family has noticed a big difference.
Although still has to use a wheelchair, she can now take a few steps on her crutches, something she could never manage before.
"This is the best Leah has ever been. We have noticed a vast difference in her," said her grandmother Wendy Ellis, who always accompanies Leah on her three-day visits to Sheffield Children's Hospital.
"She always had lots of fractures, but she hasn't had one since she started this treatment; she is growing too, and is generally stronger in every way. We're absolutely delighted."
