Race-neutral Pediatric Reference Ranges for Bone Mineral Density Predict Prospective Fractures in Childhood

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 mixedeffect 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.