Special Care Clinic Dwarfism Research

How can an orthopedic center provide next-level care for kids with a range of rare bone diseases?

Children’s Hospital Colorado is home to one of the largest pediatric orthopedic centers in the country offering comprehensive support for skeletal dysplasia and other genetic bone diseases. Through clinical trials, precision medicine and a multidisciplinary clinic, this full-service program tailors treatment to each child’s condition to provide a level of care unlike ever before.

Clinical trials for osteogenesis imperfecta

As Chair of Pediatric Orthopedics, Klane K. White, MD researches osteogenesis imperfecta, a genetic disease in which a child’s bones are brittle and break easily. Traditionally, treatment for osteogenesis imperfecta has relied on generic bone-building drugs designed for adults with osteoporosis, in combination with physiotherapy, pain treatment and acute fracture treatment. Though effective, these treatments are not tailored to this condition or its genetic origins.

To improve the treatment protocol, Dr. White became involved in two clinical trials exploring the use of the drug setrusumab, which aims to increase bone mineral density. The first trial is part of the Orbit study and is aimed at treating patients aged 5 to 25. Now in phase 3 trials, it has shown a 14% average increase in bone mineral density and a 67% reduction in annual fracture rates. Meanwhile, the second trial, called the Cosmic study, is comparing setrusumab to intravenous bisphosphonate (IV-BP) therapy in patients ages 2 to 7. “These new therapies are more directed at the actual biology of bone growth information,” Dr. White explains. “There may be hope for them that this will improve their long-term health and outcomes directly.”

Using precision medicine to better understand achondroplasia

In addition to that work, Dr. White also researches achondroplasia, a genetic condition that slows bone growth and results in shorter limbs. While the mechanisms behind this type of skeletal dysplasia are understood, it has remained difficult to study the wide-ranging, and often lifelong, comorbidities associated with the condition, including arthritis, sleep apnea, back pain, hearing loss and obesity. While achondroplasia treatments are intended to encourage bone growth, the goal of Dr. White’s research isn’t just to help children with this condition grow taller, but to understand how increasing a person’s height might mitigate challenging and painful symptoms and improve quality of life.

Despite the many advancements made possible by clinical trials, they typically don’t last long enough to measure meaningful results. “The problem is that there’s no way to demonstrate improvement in health outcomes or health-related outcomes in six to 12 months, which is the timeline for these trials,” Dr. White says. To overcome the limitations of traditional trials, he’s teaming up with a colleague at Johns Hopkins University to develop a first-of-its-kind biobank that will house the DNA of achondroplasia patients across the U.S. By merging with a national multicenter study group, which houses clinical data on more than 1,000 patients, the biobank will allow researchers to examine and better understand trends in DNA.

“We can look at the data and start finding patterns within certain presentations,” Dr. White says. “If we take a group of patients who have significant spine problems, then we can say, ‘OK, is there a commonality in their genome?’”

This will help the team at Children’s Colorado build a stronger understanding of biochemical processes, improving its ability to address specific genetic differences. “Working with this robust clinical database and collecting DNA is going to give us the opportunity to provide precision medicine therapies in the future,” Dr. White says.

Such work could hasten the delivery of new treatments, too. For example, infants born with achondroplasia have a 7% sudden death rate, but this statistic could be reduced by using this data to partner with the Colorado Fetal Care Center to diagnose the condition prenatally. “Theoretically, if we can get that DNA, we can sequence it, do a risk profile on it, and then know whether a child is at risk,” Dr. White says. “At some point, we could have very targeted therapies to help with their growth and help prevent these fatalities and complications.”

A multidisciplinary clinic for skeletal dysplasia

The Children’s Colorado Special Care Clinic is the largest of its kind nationwide, serving more than 5,000 patients annually. Geneticist Ellen Roy Elias, MD, who serves as Clinic Director, cares for children with skeletal dysplasia and those with a range of other rare bone diseases. Working alongside orthopedic providers, physical therapists, sleep specialists, nurses, dieticians and more, Dr. Elias brings her understanding of genetics to patients in the clinic to help care for their inherited, underlying medical conditions. “There are a lot of medically complicated things that can happen for these patients,” Dr. Elias says. “It’s really important to know all about that, so that when the patients come here, we can make sure we know what they need.”

Another unique aspect of the Special Care Clinic at Children’s Colorado is that it respects families who take pride in their genetic differences, some of whom don’t want to focus on growth therapies solely for the sake of societal acceptance. In these instances, the team supports patients by helping improve their overall health and quality of life.

“I think to be a full-service skeletal dysplasia program, we need to be able to offer these treatments to families who are interested, and for those who aren’t, to say that’s an acceptable and respected choice,” Dr. White says.

Dr. Elias adds that her team helps foster education among pediatricians and families regarding nutrition and growth development. For instance, many pediatricians don’t know there is a special growth curve for children with skeletal dysplasia, but using this baseline is essential to ensuring these children are developing in a healthy way.

“In the multidisciplinary skeletal dysplasia clinic, we actually care for many different kinds of diagnoses,” Dr. Elias says. “Knowing what the underlying genetic diagnosis is can totally change how we care for these kids.”