In the past decade, clinicians have made significant advancements in the diagnosis of pediatric bone disorders, particularly because national reference data is now available for bone density in children older than 5; however, clinicians do not have the appropriate tools for bone health assessment and research in early childhood.
A study at The Children’s Hospital of Philadelphia aims to address this gap by establishing reference data for children ages 1 to 5 using dual-energy X-ray absorptiometry (DXA), a test that measures bone density. The investigators also will examine factors that influence bone density and bone mineral accrual in this age group. Identifying children at risk for bone fragility is important because inadequate bone accretion may have lifelong consequences, such as susceptibility to fractures and osteoporosis.
“The first main goal of the study is to develop the equivalent of a growth chart for bone density,” said Babette Zemel, PhD, who is a co-principal investigator of the study. “Clinicians will be able to request a DXA scan, interpret it, and get an idea of where a child is relative to normal children of the same age, sex, and ancestry.”
Many serious clinical conditions in childhood threaten bone health due to inflammation and malabsorption, for example major cardiac disease, liver disease, and pulmonary disease. Or a child may have primary bone disorder that is genetic, such as osteogenesis imperfecta, which is characterized by bones that break easily, often from little or no apparent cause. Also, some young children with neuromuscular conditions have delayed gross motor skills and restricted mobility that may adversely affect bone accrual.
Accurate reference data will allow clinicians to identify bone deficits in these patient groups and to monitor how well treatment is working.
“It’s one thing for a healthy child to be running around, fall down, and break a bone, but there are some children who have pretty serious health problems, and they’re just not gaining bone the way that they should,” said Dr. Zemel, who is part of the division of gastroenterology, hepatology, and nutrition at CHOP and a research professor of pediatrics with the Perelman School of Medicine’s Institute for Translational Medicine and Therapeutics.
To give an idea of the scope of the problem posed by compromised bone strength, the Center for Bone Health team at CHOP looked at how many of the patients that they had treated who had already experienced a fracture, and it was more than 30 percent, Dr. Zemel said.
One of the challenges to conducting the current study is that toddlers cannot stay still long enough to complete a full body DXA scan. Dr. Zemel and her research team will use the latest generation of DXA technology, which provides more enhanced resolution that improves the accuracy for measuring small, less dense bones. They will conduct regional scans of the lumbar spine, forearm, and lateral distal femur that are feasible in young children because the scan time is 30 to 60 seconds, and the child can be held still without interfering with the scan.
Dr. Zemel anticipates that participant enrollment will open in April at two study sites — CHOP and Cincinnati’s Children’s Hospital Medical Center (CCHMC). Half of the study’s sample population will be African-American, and the other half will be non-African American. The study will involve a longitudinal cohort that will consist of 280 children ages 1 to 2 years who will be evaluated every six months for three years, resulting in data spanning ages 1 to 5 years. A cross-sectional cohort will include 240 children ages 1 to 1.5 years and 4.5 to 5 years who will undergo the same measurements at one time point. Data from both cohorts will be combined to create the reference curves.
Early childhood is a period of rapid development, so the researchers also will examine how changes in bone mineral content and density are related to growth, body composition, motor development, and physical activity. While previous research of older children has shown that greater growth status, more lean muscle mass, and more weight-bearing physical activity is related to higher bone density, Dr. Zemel pointed out that clinicians have little evidence that applies to the 1 to 5-year-old age range.
“With early identification of compromised bone health, improved awareness of the condition, and better understanding of the mechanisms involved, there is hope that this may soon translate into new and improved therapy for children at-risk for poor bone mineral accrual,” Dr. Zemel said.
An innovative part of the study is its application of new techniques for estimating body composition — the amount of muscle, fat, and bone in the body. A group of physicists from the University of California, San Francisco (UCSF) who are experts in bone and body composition imaging will use novel analysis to determine body composition from all of the children’s regional DXA scans, separating bone from soft tissue and air, and then calculating lean muscle and fat mass.
Since this technique is not yet validated, Dr. Zemel and her team will conduct anthropometric exams at all visits. Anthropometry is the collection of high quality body measurement data using standardized examination procedures and calibrated equipment. Trained anthropometrists will obtain skinfold thickness measurements that can be used in prediction equations, yielding excellent body composition estimates.
In a subset of 120 participants, the researchers will compare DXA and anthropometric body composition methods to the current gold standard, which uses isotope dilution to measure total body water and calculate fat and fat-free mass.