Bone disorders — from fragile bones that easily break to diseases that affect mineral metabolism and cause bone deformities or conditions resulting in short stature — can diminish a child’s quality of life and often are perplexing to clinicians. But a specialty program at UCLA Mattel Children’s Hospital, the Pediatric Bone Program, offers a multidisciplinary team approach, including pediatric orthopedic surgeons, geneticists and dentists in the evaluation and treatment.
“This is a field in which you need a team of experts, and that is the benefit of practicing in a major center such as UCLA,” says program director Isidro B. Salusky, MD, a pediatric nephrologist and a leader in the field of bone and mineral abnormalities in patients with chronic kidney disease and rare genetic bone disorders.
Among the conditions seen at the program’s clinic are childhood osteoporosis and fractures, osteogenesis imperfecta, hypophosphatemic rickets, pseudohypoparathyroidism and tumor calcinosis, as well as poor bone mineralization from disordered phosphate, calcium and vitamin D metabolism. Some patients have bone problems due to chronic conditions and immobilization, such as seizure disorders or cerebral palsy. Children with chronic kidney disease and other chronic conditions can experience complications, such as bone deformities, short stature and fractures. Post-organ transplantation, (kidney, liver and heart) patients also can develop osteoporosis and fractures, and such disorders may persist. Still others are referred because they are experiencing idiopathic fractures with minimal trauma.
“We see a wide variety of conditions, some of which have a genetic basis, and others that develop over time or are secondary to medications or other chronic medical diseases,” says Katherine Wesseling-Perry, MD, a pediatric nephrologist on the program’s medical team. “We evaluate the full spectrum of disorders.”
The evaluation process begins with a history and physical exam, including specific blood tests, and often includes dual-energy X-ray absorptiometry (DEXA) scans to measure bone mineral density or more sophisticated bone density tests for children with growth delay, Dr. Wesseling-Perry explains. Blood tests assessing calcium phosphate, vitamin D nutrition and other biomarkers help to determine if a problem with mineral metabolism is contributing to the disease, and further lab tests also can be ordered to determine the cause of bone fragility.
For cases that continue to defy diagnosis, UCLA is among the few centers in the country that is qualified to perform and interpret bone biopsy through a sophisticated technique in which a small piece of bone is removed from the iliac crest and sent to the bone histomorphometry laboratory for analysis. “Through both traditional bone histomorphometry and immunohistochemistry, we learn about the basic pathology of bone and see how specific proteins are expressed at the bone level, and whether or not they have a role in the disease pathogenesis,” says Dr. Salusky, who heads the lab.
Effective treatments are available for most bone disorders, Dr. Wesseling-Perry notes. One of the most exciting new therapies to become available in recent years is an antibody to the fibroblast growth factor 23 (FGF23) molecule, a highly effective new therapy for patients with bone mineralization disorders, such as hypophosphatemic rickets.
“Sometimes, especially in the case of fractures, the lines can be blurred between what’s normal and what might be pathological,” Dr. Wesseling-Perry says. “In general, any concern about excess fractures, bone deformities, bone pain or a chronic condition requiring medications that can impair the bones should be referred to a specialized center for evaluation.”