Building bones and better lives

[Alison J Stevens]

Building bones and better lives

Luke Hall, Dorothy Hall, research nurse Rachel Harrison, and Professor Nick Bishop

A new trial investigating treatment of brittle bone disease in children has found that a drug used to treat osteoporosis in adults can reduce the number of fractures suffered by affected children. Jane Tadman talks to the doctor who ran the study, and to one of the youngsters who took part.

Diagnosed with the brittle bone disease osteogenesis imperfecta before he was even born, Luke Hall’s mother says she stopped counting how many fractures he had during his childhood when it got to 40. But Luke is one of the lucky ones.

Luke, from Leeds, is not classed as having severe brittle bone disease. Now aged 14, he looks like any other teenager, and he leads a normal, active life. Like many affected youngsters Luke has a higher than normal pain threshold, and he has become almost blasé about fracturing bones, mainly in his legs and hands.

“When I have a fracture I don’t really bother going to hospital anymore because there’s nothing much they can do, and it means sitting around in A&E for hours,” he explains. “I usually take painkillers like ibuprofen and paracetamol, and just get on with things.”

Luke thinks the last time he had a fracture was about four months earlier. “I think I broke my wrist because it clicks, but it’s not painful any more. A couple of years ago I broke my ribs, and I went to hospital but they just told me to go away and take painkillers.”

At one point Luke had fractures in both his feet. “I dragged him to the doctor who said we were unduly worried,” remembers Luke’s mum Dorothy Hall. “Later he went for an x-ray, and walked into the x-ray department with his fractured feet and his shoes still on. The doctor couldn’t believe it when he saw the x-ray and realised what pain he must have been in.”

Dorothy knew her son had a one-in-two chance of being born with osteogenesis imperfecta because her husband, Luke’s dad Kevin, also had a mild version of the condition. “I knew from my first scan that he had it, and they identified that he had fractures when he was in the womb, so I had to have a caesarian which was the safest thing to do,” she says.

Luke was looked after at the child development centre at St James’s Hospital in Leeds, but no drug treatment was available and it wasn’t until Luke was nine that by chance Dorothy heard about the clinic run by Professor Nick Bishop at Sheffield Children’s Hospital.

At that time Professor Bishop, an internationally renowned expert in brittle bone disease in children, had recently arrived from Cambridge to take up a post of Professor of Paediatric Bone Disease at Sheffield University. He was also just setting up a clinical trial, funded by Arthritis Research UK, to find out if giving affected children drugs used to treat osteoporosis in adults – bisphosphonates – could reduce the number of fractures they suffered.

The Halls were happy for Luke to take part in the trial, and from then on he took a weekly tablet of risedronate.

More than 50 children with osteogenesis imperfecta took part in the Arthritis Research UK trial, the results of which are about to be published in the Journal of Bone and Mineral Research.

Previous research by Professor Bishop had shown that an intravenous bisphosphonate called pamidronate increased children’s bone density by up to 40 per cent, and the trial results from this latest study confirmed that risedronate increased bone mass and reduced bowing deformities of the limbs.

Parents tell us that their child has more energy”

“All children on the trial experienced a reduction in fracture risk and there was no specific difference between the top and bottom dosage groups,” says Professor Bishop. “We learnt that the dosage of treatment you give is important in increasing bone mass, but we cannot honestly be sure about the dose of treatment and the reduction in fracture risk.”

However, the trial has established that a dose of 2mg a week will reduce the risk of fracture and keep children’s bone pain under control. Professor Bishop says: “When we stopped their treatment at the end of the trial (we stop their treatment for six months in case they run into any side-effects) many of the children came back to us before the six months were up complaining that they did not feel well, and wanting to be back on the treatment. The drug made them feel better in themselves. Parents tell us that their child has more energy when on the treatment, and are happier, not so grumpy.”

Luke Hall and Professor Bishop

Professor Bishop believes that the take home message from the trial is that for children with a milder form of osteogenesis imperfecta, risedronate is a perfectly reasonable way to treat them. However, for severely affected children, babies or adolescents at the end of their period of growth, then intravenous pamidronate is a better first-line option. “It’s taken us seven years to find out but this is a big step forward, as it helps us to tell what is best for the patient. We need to target risedronate appropriately, and not use it as a first-line treatment for all children.”

Dorothy Hall thinks that since Luke has been on risedronate his energy levels have gone up. “He can do more, and has more of an appetite. As he has got older he has become more aware of his limitations and takes a bit more care, and is less likely to have as many fractures, although whether that’s due to the drugs or his attitude we’re not sure. DXA scans have shown that Luke’s bones have got thicker.”

Nick Bishop says he encourages children to take part in sport as it’s good for their self-esteem, and while there is a risk of fracture, there’s a balance to be struck between wrapping children in cotton wool, and letting them get on with life.

Luke Hall definitely takes the latter view. “I can’t go on a trampoline, go ski-ing or play rugby but I wouldn’t want to anyway,” he says. “I played football until recently, and if I’d wanted to I would have carried on – I didn’t stop because of having brittle bones. I watch what I do. But I still do things. Having brittle bones is annoying, but it doesn’t stop me doing much.”

What is osteogenesis imperfecta?

Osteogenesis imperfecta affects one in 15,000 children. There are about 14 new cases a year, with the majority at the milder end of the spectrum. Children with more severe disease have enormous needs, with their height restricted, and spending much time in wheelchairs. When Professor Bishop started his clinic in Sheffield, the projection was that his patient cohort would be around 125. The number is now 275. Sheffield is one of the main centres in the UK and treats more children than Great Ormond Street Hospital, with children referred from all over the UK, typically by a paediatrician.

“I think there may be more cases than we know about, and recognition is still quite low; many orthopodaedic surgeons still refer cases quite late on,” says Nick Bishop. “If a doctor thinks a child has brittle bone disease he or she should get them seen by a specialist team because they have a lot to offer. Early diagnosis and treatment are very important especially when we need to reconstitute the vertebrae – you can only treat children before they stop growing, so there is a limited window of opportunity.

“We get children from around the time of birth, who need treatment within the first four weeks of their life, children with recurrent fractures or those with a family history, children who were told there was nothing could be done for them. We have a major job of education that we try to do.

“A child with mild osteogenesis imperfecta could expect between five and ten fractures in their lifetime, with moderate disease between 30 and 50, and with severe disease 200 and 300 if untreated. We can substantially reduce that number, but we cannot stop them completely.

“In all the time I have been in Sheffield we have never lost a single child even though they have been extremely ill. In the old days, severely affected infants would have died by the time they were six months old. We have helped them through, although often with significant physical disabilities, and they can do more, and be more independent and mobile. As a result of a multi-disciplinary team approach they receive medical therapy, occupational therapy, physical therapy, education, support for their family, and close liaison with other services like school and social care. It’s a disease that affects many areas of the children’s lives.”