Imagine having a skeleton so fragile a sneeze could land you in the ER with a broken bone. For people with osteogenesis imperfecta (OI), a rare genetic disorder characterized by brittle bones due to inadequate or imperfectly formed collagen, fracturing without trauma or a even a known cause can be both routine and excruciatingly painful.
An estimated 20,000-50,000 people in the United States live with OI, including a good friend who has endured more than 90 fractures and 25 surgeries in 31 years, and once broke his arm by simply waving goodbye. The disorder is classified in four types by severity and presents symptoms that vary by person but may include short stature, spinal curvature and loose joints as well as dental, respiratory and hearing problems.
Standard treatment for children diagnosed with the condition may include physical therapy, wearing braces, and using a wheelchair or other assisting device. Rodding—surgically inserting metal bars to support long bones—may help to prevent injury and deformity in the limbs, but rods must continually be exchanged for larger sizes as children grow. More trips to the hospital could include intravenous treatments with bisphosphonates, a class of drugs shown to reduce fractures in adults with osteoporosis. Both oral and intravenous bisphosphonates have been tested in small pediatric studies to help boost bone mineral density and reduce fractures. One study found that alendronate (an oral bisphosphonate) was no better than placebo at reducing bone pain or fractures in OI. For this reason, intravenous bisphosphonates have been the mainstay of therapy used for compassionate treatment of children with moderate to severe OI and fractures.
But a new study published in The Lancet suggests that risedronate, a different oral bisphosphonate, may reduce fractures in children with OI. An international team, including researchers from the University of Sheffield and Sheffield Children’s Hospital, conducted a clinical trial of 147 children, ages 4 to 15. Ninety-seven participants received a daily dose of risedronate for one year while 50 received a placebo, but all the children were given the drug for two more years during an open-label extension. Medical Daily reports:
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.
Study authors concluded that oral risedronate should be considered as a home-treatment option for children with OI.
Laura Bachrach, MD, is a professor of pediatric endocrinology at Stanford who researches optimal therapies for children with bone fragility. I asked Bachrach for her thoughts on the study. She commented:
The investigators are to be commended for conducting this rigorous drug treatment study in children. Too often, the investment of time and money needed to adequately test drugs is not made and practitioners must extrapolate from adult data when treating children. Although this study showed risedronate to be effective in reducing non-spine fractures in children with mild disease, it leaves unanswered several important questions. How will it work in those with moderate to severe disease where quality of life is most compromised? In these children, it is critical to prevent the vertebral fractures that lead to deformed spines and smaller lung capacity. Will risedronate prove powerful enough to prevent spine and limb fractures in those more severely affected? Although it would not be ethical to conduct a placebo-controlled trial in moderate to severe OI, a randomized comparison of risedronate and one of the intravenous drugs used in OI (pamidronate and zoledronic acid) would answer these important questions.
Previously: Stanford study shows protein bath may rev up sluggish bone-forming cells, New genetic regions associated with osteoporosis and bone fracture, Iron-supplement-slurping stem cells can be transplanted, then tracked to make sure they’re making new knees and Collaboration between Stanford and UCSF aims to advance arthritis research