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Horacio Plotkin, M.D. |
The assistant professor of pediatrics has developed a reputation among patients and families as a compassionate, “plucky” physician.
“I go against the tide — many times against the system — but I do it for my patients,” said the pediatric endocrinologist at UNMC’s Munroe-Meyer Institute.
In the world of academic medicine, Dr. Plotkin’s youth, tenacity and unconventional ideas make him stand out like a scarlet tanager amid a flock of blue jays.
“When I first tried to publish a new classification for O.I. (osteogenesis imperfecta — a genetic bone disease), it was a new idea that didn’t go over so well,” Dr. Plotkin said. “It took more than two years, and many rejections, but that didn’t matter because when something is important, I never give up.”
His latest research project, a pilot study published in the September issue of Developmental Medicine and Child Neurology, was picked up by the international news agency, Reuters.
The study involved non-ambulatory children with severe cerebral palsy, who received low doses of intravenous pamidronate, a bisphosphonate drug. After 12 months of treatment, the children showed significant increases in bone mineral density.
The incidence of bone fractures in kids with severe cerebral palsy is more than twice as high as in the normal population. Yet few researchers are investigating bone density problems in this group of patients, and fewer treatment centers offer therapeutic or preventive treatments.
“At our bone clinic here in Omaha, we routinely offer this (IV pamidronate) treatment to kids with severe cerebral palsy. Many of these patients can’t talk, but they can tell you when they’re in pain. When they break a bone, they cry — it’s extremely painful,” Dr. Plotkin said.
Results of his pilot study must be verified by larger, multi-center trials. However, he said, “If we can prove low-dose pamidronate helps prevent bone fractures in this population, it could become standard of care. It will be one of few things we can fix in kids with severe cerebral palsy.”
Dr. Plotkin’s expertise in pediatric bone disorders has brought patients from as far as Romania, Spain and Mexico to Omaha, where he treats about four new patients every month.
His long history of studying bisphosphonate drugs, like pamidronate, in children with bone disorders began in the early 1990s. Bisphosphonates are believed to work by preventing the normal breakdown of bone, thus increasing bone density. This class of drugs is widely prescribed to prevent and treat osteoporosis.
In the mid 90s, Dr. Plotkin was part of the Canadian research team, which began using intravenous bisphosphonates in children with O.I.
Children with severe O.I. have such weak, fragile bones that they often break for no apparent reason. In the most severe cases, O.I. is fatal.
The Canadian study, published in the New England Journal of Medicine in 1996, showed for the first time there was a medical treatment that could successfully increase bone density and decrease painful and disabling bone fractures caused by severe O.I.
But the dosages of IV pamidronate used in this early study were more than twice as high as the doses used in Dr. Plotkin’s latest study on kids with cerebral palsy. The high-dose IV regimen is now commonly prescribed for patients with severe O.I.
But since there are no placebo-controlled trials, the use is off-label and questions about the long-term risks and benefits are difficult to answer.
For example, some of the children in the Canadian study developed rigidity in their bones, putting them at risk of breaking again. When treatment was discontinued for that reason, the new bone that formed in these children was once again weak and fragile.
It became clear that severely affected O.I. patients would have to continue IV treatments to keep producing stronger bones, but remaining on high-dose therapy for too long also could lead to excessive bone density. Dr. Plotkin began to question whether the dosages used in the Canadian study were too high.
When he arrived at UNMC in 2002, he began developing a new research protocol using just half the usual dosage of IV pamidronate. Dr. Plotkin’s latest study in cerebral palsy patients is the first to suggest the low-dose protocol can effectively and successfully increase very low bone density in children.
The low-dose regimen has been dubbed the “Omaha Protocol” and is frequently requested by physicians all over the world who treat pediatric bone disorders.
Dr. Plotkin hopes additional data will prove the Omaha Protocol also prevents the exaggerated increase in bone density seen with high-dose therapy, and therefore involves less risk to the patient.
In an accompanying editorial to the study, Richard Henderson, M.D., professor of orthopedics and pediatrics at the University of North Carolina School of Medicine, commends Dr. Plotkin and colleagues, saying, “The series is reasonably large and the study was conducted by physician investigators at the forefront of the field. This is clinically, scientifically, and ethically quite different than the rapidly growing number of well-intentioned physicians who are ‘trying’ bisphosphonates on a few children.”
Without necessary funding for controlled clinical trials, Dr. Henderson recommends more published experience with bisphosphonates before they become “standard care” for treating very low bone density in children.