Could Race-Neutral Reference Ranges Predict Prospective Fractures in Children?

By Kate Knab

The Findings

Researchers developed the first race-neutral pediatric reference ranges for areal bone mineral density (BMD) at multiple skeletal sites and spine bone mineral apparent density (BMAD) for children ages 5 to 20 representative of the race/ethnicity distribution across the United States. These reference ranges are used to calculate Z-scores (standard deviation scores) that aid in assessing bone health in children. Previous reference ranges were race-specific.

Across race/ethnicity groups, researchers found differences in Z-scores using the race-neutral reference ranges that were modest for most groups. However, on average children who identified as Black had greater Z-scores, which were partly attributable to differences in height and lean mass.

Importantly, researchers found that the race-neutral reference ranges were better than race-specific reference ranges at predicting subsequent fractures in a group of over 2,000 healthy children. Spine BMAD and BMD of the 1/3 distal radius were the best predictors of incident fractures.

Why It Matters

Bone mineral accrual during growth is important to establish lifelong skeletal health, and having appropriate reference ranges is critical for bone health evaluation during childhood and adolescence. Although previous BMD reference ranges for children typically included age, sex, and race-specific data, the national growth charts for height, weight, and body mass index are race-neutral. This study evaluated whether growth charts for BMD also should be race-neutral.

Few studies have tested whether BMD Z-scores can predict subsequent fractures. This is the first study to determine whether race-specific or race-neutral reference ranges are better in predicting and interpreting childhood fracture risk.

Who Conducted the Study

The first author of this multicenter study was Babette Zemel, PhD, a professor of Pediatrics at the University of Pennsylvania Perelman School of Medicine and investigator in the Division of Gastroenterology, Hepatology and Nutrition. Dr. Zemel worked alongside co-author and division colleague, Jonathan Mitchell, PhD. Researchers from the Division of Endocrinology and Diabetes who contributed include Attending Physician Andi Kelly, MD, MSCE; Assistant Professor of Endocrinology, David Weber, MD, MSCE; Attending Physician, Shana McCormack, MD, MTR; and Director of the Center for Spatial and Functional Genomics at CHOP, Struan Grant, PhD, along with contributors from the National Institutes of Health, the University of Pennsylvania, Columbia University, University of Hawaii, and Cincinnati Children’s Hospital Medical Center.

How They Did It

In a secondary analysis of data from the National Institute of Child Health and Human Development Bone Mineral Density in Childhood Study, researchers analyzed BMD and BMAD data on the spine, hip, forearm, and total body (excluding the head) from dual-energy X-ray absorptiometry scans, which measure body composition and bone density. This data was collected from 2,104 participants over seven years. Race/ethnicity, dietary calcium, physical activity, and prior prospective fractures were assessed by questionnaire.

To generate the race-neutral reference ranges and adjust the height-for-age Z-scores, researchers used a statistical technique called the lambda-mu-sigma method to create percentile curves. Cox proportional hazard modeling tested whether race-neutral Z-scores associate with fracture risk as compared to race-specific Z-scores.

Quick Thoughts

“In this study, we show the benefit of using race-neutral reference ranges in predicting subsequent fracture and which BMD measures are the best predictors,” Dr. Zemel said. “These findings provide a strong foundation for more evidenced-based recommendations for using bone density in skeletal health evaluations in children.”

What’s Next

Future studies could further validate whether the adoption of race-neutral BMD reference ranges would apply to all children, especially those of multiracial identity who represent a growing percentage of the U.S. population, and children with risk factors for poor bone mineral accrual.

Where the Study Was Published

The study appears in The Journal of Clinical Endocrinology & Metabolism