Drs. Margaret Marks (left) and Ambika Ashraf lead the metabolic bone disease clinic at Children’s of Alabama.
Treating metabolic bone disease in children involves a team of specialists including a pediatric endocrinologist, pediatric orthopedic surgeon, geneticist, physical medicine rehabilitation specialist and nutritionist. Where once patients and their families had to navigate this web of specialists, now the metabolic bone disease clinic at Children’s of Alabama assembles the entire care team, whom patients often see in one visit, thanks to a multidisciplinary approach.
“When we initially started out, we weren’t sure how many patients we’d have,” clinic director Ambika Ashraf, M.D., said. “Subsequently, we realized most of these patients were going out of state.” Today, the clinic follows more than 300 patients. Most are from Alabama, but patients also travel from Tennessee, Mississippi and Georgia.
Since most of the conditions the clinic sees are complex and require multidisciplinary care, “getting to see the different specialists on the same day is a huge benefit,” Ashraf said. Otherwise, it could take six to eight months to get an appointment with individual specialists.
Patients have a varied spectrum of conditions including osteogenesis imperfecta; fibrous dysplasia; complex disorders of calcium, phosphorous and vitamin D metabolism; fragility fractures due to low bone density and osteoporosis; hypophosphatasia; and skeletal dysplasias.
Pediatric metabolic bone disease spans a spectrum from mild disease with a relatively low risk of fractures to disease so severe that just a small bump could result in a broken bone. Despite treatment, patients tend to be small in stature for their age, with multiple deformities resulting from fractures and poor healing, Ashraf said. They are also prone to problems in other areas, including cardiovascular and pulmonary complications. “We make sure they see those specialists, too,” she said.
The most common condition the clinic treats is osteogenesis imperfecta (OI), or brittle bone disease, a genetic defect that affects the body’s ability to make collagen, which is required for strong bones. These children may have dozens or even hundreds of fractures before they reach adolescence.Most patients with OI receive bisphosphonate infusions in the Children’s infusion center to strengthen their bones.
Physical medicine, or physiatry, plays an important part in managing these children, Ashraf said, because many have some type of abnormality related to muscle tone or movement, joint laxity, joint contractures or muscle weakness. They may also need help with a wheelchair, braces/splints or other mobility devices.
“This is a fascinating time for metabolic bone disease,” Ashraf said. Just a decade ago, there were few treatments beyond the supportive and palliative. For instance, until a few years ago, the only treatments for X-linked hypophosphatemic rickets were oral phosphate and calcitriol. They helped, but not enough, and patients still required frequent surgeries. With the availability of burosumab, a monoclonal antibody that binds to and inhibits the activity of fibroblast growth factor 23—which blocks phosphate absorption—children with the condition now need fewer surgeries and experience fewer limb deformities.
Bisphosphonate infusions help reduce the number and severity of fractures in OI patients, and physical therapy can help with deformities. For hypophosphatasia, enzyme replacement helps manage the condition. Caring for these children “is a joy,” Ashraf said. “Especially when we can make a difference in their quality of life.”