(From the January 2015 Issue of PediatricsOnline)
Osteogenesis imperfecta (OI) is a genetic disorder characterized by bone fragility and low bone mass, which often lead to frequent fractures during childhood. Traditionally, the condition has been managed with surgery and orthotics, but medications to improve bone mass and strength have gained popularity in the last couple of decades. Now, research performed by clinician-scientists in the Metabolic Bone Clinic at Nationwide Children’s Hospital indicates that intravenous pamidronate may be a safe and effective pharmaceutical treatment for fracture prevention that can be administered as early as the first month of life in children with OI.
Collectively, the eight forms of OI have an incidence of one in every 10,000 births, with type I being the mildest, type II typically being fatal in the neonatal period and the remaining types varying in severity. Bisphosphonates are now a common treatment for patients with OI due to their ability to prevent bone degeneration and even spur new bone production. Pamidronate, a type of bisphosphonate, is a drug used to treat bone damage caused by a variety of diseases, including cancer.
“Back in 2000, we started cyclical IV pamidronate administration treatment with children with severe OI and multiple fractures,” says John D. Mahan, MD, director of the Metabolic Bone Clinic, nephrologist and researcher at Nationwide Children’s, and senior author on the study, which was published in the Journal of Bone and Mineral Metabolism. “The results were so good, we extended the treatment approach to even the youngest children to see if it would similarly increase their lumbar spine areal bone mineral density.”
The clinical research team performed a retrospective chart review of 18 patients to examine the treatment’s safety and efficacy in infants. Five patients had OI type I, seven had type III, and six had type IV. Age at initial treatment ranged from 11 days to 23 months, and children received pamidronate intravenously in three-day cycles. Lumbar bone mineral density, fracture numbers and child growth were charted before and after the therapy was administered. Children were followed for an average of 73 months post-treatment prior to publication of the results.
“The fracture rate improved significantly,” Dr. Mahan says. “The group experienced an average of 0.32 fractures per patient-month before treatment and only 0.03 fractures per patient-month after treatment.”
Mean lumbar bone mineral density also improved, from -3.63 standard deviations below normal at baseline to -1.53 at one year post-treatment and 0.79 by study’s end. Linear growth was not impacted by the treatment, and the only adverse effect noted was a fever, which occurred during the first pamidronate infusion in six infants.
“Overall, the therapy was successful at reducing morbidity in infants with osteogenesis imperfecta,” explains Dr. Mahan, who is also a professor of Pediatrics at The Ohio State University College of Medicine. “The fact that it prevented fractures and improved bone mineral density while preserving linear growth makes it an attractive treatment option. Now we know that infants with OI can safely get IV pamidronate therapy early, before fractures and problems like the need for major bone surgeries inevitably occur.”
According to Dr. Mahan and his collaborators in the Metabolic Bone Clinic, extended follow-up of these children is crucial, since researchers do not yet know how pamidronate infusions during infancy may impact long-term growth, bone health and OI-related morbidity.
“Having colleagues with multiple discipline knowledge and skills allows us to provide more comprehensive and effective evaluations and care for children with OI and other metabolic bone conditions,” Dr. Mahan says of the Metabolic Bone Clinic. “Genetic, endocrine and nephrologic care couple with consulting dentists, sports medical specialists and our nurse clinicians and nurse practitioners to help our patients by coordinating their complex care.”
Dr. Mahan is also currently involved with investigations on the use of growth hormone for children with OI who have delayed growth associated with their OI subtype.
Kusumi K, Ayoob R, Bowden SA, Ingraham S, Mahan JD. Beneficial effects of intravenous pamidronate treatment in children with osteogenesis imperfecta under 24 months of age. Journal of Bone and Mineral Metabolism. 2014 Oct 16. [Epub ahead of print]