Risedronate Clinical Trial Shows Rapid Relief For Children With Osteogenesis Imperfecta: A New Hope For Kids With Brittle Bones?
Children with osteogenesis imperfecta live under the constant threat of breaking their bones, but a relatively new drug, risedronate, has rejuvenated hopes that the pediatric disease can be treated. The risk of bone fracture dropped in kids taking the drug in as little as six weeks, according to a Phase III clinical trial reported this week in the journal Lancet.
Osteogenesis imperfecta strikes about one in 20,000 kids, but even with mild cases, the risk of breaking a long bone — like a femur, tibia, or ulna — is about 100 times higher than the general population. Nearly three out of four children with the disorder suffer a spinal injury at some point, while several others have deformed limbs.
In this study, led by researchers at the University of Sheffield, 147 pediatric patients with mild forms of the disease were randomly assigned a year-long regimen of either a placebo or the drug risedronate.
Risedronate is a next-gen member of a class of drugs called bisphosphonates. Previously used to treat osteoporosis in adults, the drugs are now being explored as a way to increase bone mineral density in children.
Smallers studies had been conducted with risedronate, with mixed results in terms of reducing the rate of bone fractures, so the researchers are Sheffield, in league with an international team of doctors, decided to conduct a larger, more comprehensive clinical trial.
The oral medication reduced fractures in non-spinal bones by nearly 20 percent over the course of the year. A subgroup continued taking risedronate for another two years and witnessed similar beneficial rates of less injury. This improvement was correlated with better bone density.
“We wanted to show that the use of risedronate could significantly impact on children's lives by reducing fracture rates — and it did,” said lead author Dr. Nick Bishop, professor of pediatric bone disease at the University of Sheffield. “The fact that this medicine can be given by mouth at home (other similar medicines are given by a drip in hospital) makes it family-friendly.”
Risedronate: A New Hope For Brittle Bone Disease?
Despite these exciting results, questions still remain as to whether risedronate could prevent severe injuries. Rates of spinal fractures were not reduced in this trial, which examined mild cases and not the most severe varieties of the disease.
“Where do these new data leave us with respect to the treatment of children with osteogenesis imperfecta?” wrote Drs. Leanne Ward and Frank Rauch of the Children’s Hospital of Eastern Ontario in an associated commentary in Lancet. “Bishop and colleagues’ study included few children with severe osteogenesis imperfecta, and therefore does not provide substantial new evidence for the treatment of severe disease.”
“For children and adolescents with mild osteogenesis imperfecta, oral risedronate emerges from this study as an option to reduce the number of nonvertebral fractures, although whether it reduces longbone fractures, which have the highest clinical morbidity, remains unclear," they continued.
However, many of these questions will only be answered after more trials with risedronate are conducted. In addition, the drug does open a new option for relief for those with a mild form of the disease, namely because this drug is oral and easier to administer than other bisphosphonates, which are given intravenously.
“Oral risedronate treatment significantly reduced the risk of clinical fracture in children with osteogenesis imperfecta in this study,” wrote Bishop and colleagues. “Risedronate should be regarded as a treatment option for children with osteogenesis imperfecta.”
Sources: Bishop N, Adami S, Ahmed SF, et al. Risedronate in children with osteogenesis imperfecta: a randomised, double-blind, placebo-controlled trial. Lancet. 2013.
Ward LM, Rauch F. Oral bisphosphonates for paediatric osteogenesis imperfecta? Lancet. 2013.