Race-neutral Pediatric Reference Ranges for Bone Mineral Density Predict Prospective Fractures in Childhood
Babette S. Zemel, Karen K. Winer, Andrea Kelly, David S. Freedman, Jonathan A. Mitchell, David R. Weber, Shana E. McCormack, Tara McWilliams, Joan M. Lappe, Sharon E. Oberfield, John Shepherd, Struan F.A. Grant, Heidi J. Kalkwarf
Abstract
INTRODUCTION: Race-specific reference ranges for pediatric areal bone mineral density (BMD) are widely used, but the value of race-based clinical algorithms has been questioned. We developed race-neutral pediatric reference ranges for areal BMD and bone mineral apparent density (BMAD) and compared race-specific vs race-neutral Z-scores in their ability to predict prospective fractures. MATERIAL AND METHODS: This secondary analysis of the Bone Mineral Density in Childhood Study used longitudinal BMD data of the spine, hip, forearm, and total body less head and BMAD from dual-energy x-ray absorptiometry (DXA) scans. Race/ethnicity, dietary calcium, physical activity, and prospective fractures were assessed by questionnaire. Race-neutral reference ranges and height-for-age Z-score adjustment equations were created using the lambda-sigma-mu method. Race-neutral and race-specific Z-scores were compared using linear mixed-effect modeling. Cox proportional hazard modeling was used to test whether race-neutral Z-scores associated with fracture. RESULTS: Race-neutral BMD and BMAD Z-scores were 0.5 to 0.7 SD greater than race-specific Z-scores for Black children but only ∼0.1 SD lower for children from other race/ethnicity groups. Growth and lifestyle factors modified group differences. One SD increase in race-neutral Z-scores was associated with a 12% to 18% reduced risk of fracture. CONCLUSION: We present the first race-neutral pediatric reference ranges for BMD and BMAD that are weighted to be representative of the US population and demonstrate that these Z-scores associate with fracture risk. Adoption of these new reference ranges should be considered, with thoughtful implementation for patients previously monitored with race-specific reference ranges, especially among children who identify as Black.