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. 2025 Oct 16;110(11):3034-3048.
doi: 10.1210/clinem/dgaf183.

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

Babette S Zemel  1   2 , Karen K Winer  3 , Andrea Kelly  2   4 , David S Freedman  5 , Jonathan A Mitchell  1   2 , David R Weber  2   4 , Shana E McCormack  2   4 , Tara McWilliams  6 , Joan M Lappe  7 , Sharon E Oberfield  8 , John A Shepherd  9 , Struan F A Grant  2   4   10   11 , Heidi J Kalkwarf  12
Affiliations

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

Babette S Zemel et al. J Clin Endocrinol Metab. .

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.

Keywords: BMAD; BMD; children; fracture.

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Figures

Figure 1.
Figure 1.
Reference ranges for race-neutral Z-scores for (A) spine BMD, (B) spine BMAD, and (C) total body less head BMD. Shown are the curves for −2 SD, −1 SD, the median, + 1 SD, and +2 SD. Abbreviations: BMAD, bone mineral apparent density; BMD, bone mineral density.
Figure 2.
Figure 2.
Distributions of race-specific and race-neutral Z-scores by race/ethnicity groups for (A) spine BMD, (B) spine BMAD, and (C) total body less head BMD. Shown are the mean values and 95% confidence intervals. Abbreviations: BMAD, bone mineral apparent density; BMD, bone mineral density.
Figure 3.
Figure 3.
Mean race-neutral Z-scores by race/ethnicity groups without adjustment and with sequential adjustment for calcium intake, high-impact physical activity, HAZ, and ALMI-Z for (A) spine BMD, (B) spine BMAD, and (C) total body less head BMD. Abbreviations: ALMI-Z, appendicular lean soft tissue mass index Z-score; BMAD, bone mineral apparent density; BMD, bone mineral density; HAZ, height-for-age Z-score.
Figure 4.
Figure 4.
Race-neutral BMD-for-age Z-scores compared to height-for-age adjusted BMD Z-scores for (A) spine BMD and (B) total body less head BMD. Abbreviation: BMD, bone mineral density.
See this image and copyright information in PMC

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