Context Dual-energy X-ray absorptiometry (DXA) is a cornerstone of pediatric bone health assessment, yet differences in height-for-age confound the interpretation of areal bone mineral density (aBMD) measures. To reduce the confounding of short stature on spine bone density, use of bone mineral apparent density (BMAD) and height-for-age Z-score (HAZ)‒adjusted aBMD (aBMD_HAZ) are recommended. However, spine BMAD reference data are sparse, and the degree to which BMAD and aBMD_HAZ account for height-related artifacts in bone density remains unclear. Objective We developed age-, sex-, and population ancestry‒specific spine BMAD reference ranges; compared height-adjustment methods in accounting for shorter stature; and assessed the stability of these measures over time. Design Secondary analysis of data from a previous longitudinal study. Participants Children and adolescents aged 5 to 19 years at baseline (n = 2014; 922 males; 22% black) from the Bone Mineral Density in Childhood Study. Main Outcome Measures Lumbar spine BMAD and aBMD_HAZ from DXA. Results Spine BMAD increased nonlinearly with age and was greater in blacks and females (all P < 0.001). Age-specific spine BMAD z-score reference curves were constructed for black and non‒black males and females. Overall, both BMAD and aBMD_HAZz scores reduced the confounding influence of shorter stature, but neither was consistently unbiased across all age ranges. Both BMAD and aBMD_HAZz scores tracked strongly over 6 years (r = 0.70 to 0.80; all P < 0.001). Conclusion This study provided robust spine BMAD reference ranges and demonstrated that BMAD and aBMD_HAZ partially reduced the confounding influence of shorter stature on bone density.

Context: Insulin resistance is an adverse health outcome that accompanies obesity. Fat mass is negatively associated with the bone mass after adjustment for confounders. Insulin resistance might be an intermediary in this relationship.Objective: To determine whether insulin resistance is an intermediary in the relationship between adiposity and bone mass in adolescents.Design: Cross-sectional secondary analysis of baseline data from a previous randomized trial.Setting: University research facility.Participants: A total of 240 adolescents (68% female), aged 7 to 15 years.Main Outcome Measures: Using dual energy x-ray absorptiometry, bone mineral content (BMC), areal bone mineral density, lean mass, and fat mass were measured. Skeletal sites of interest included the total body and lumbar spine (LS). Waist circumference was measured using an anthropometric tape measure. Insulin and glucose were measured in fasting sera, and the homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. Path analysis was performed to determine whether the relationship between adiposity and bone was mediated through insulin resistance.Results: Fat mass (r = 0.467; P < 0.001) and waist circumference (r = 0.487; P < 0.001) correlated positively with HOMA-IR. Controlling for race, sex, maturation, lean mass, and height, fat mass, waist circumference, and HOMA-IR were negatively associated with LS BMC and total body areal bone mineral density (P < 0.05 for all). Additionally, path models for fat mass (95% CI, −5.893 to −0.956) and waist circumference (95% CI, −15.473 to −2.124) showed a negative relationship with LS BMC via HOMA-IR.Conclusions: These results support an intermediary role of insulin resistance in the relationship between adiposity and LS bone mass.

Summary: Background and objectives: Visceral fat is associated with increased cardiovascular risk in adults, but studies in youth are limited. We assessed associations between visceral fat and arterial stiffness in youth with healthy weight, obesity and type 2 diabetes and determined whether relationships were independent of clinical estimates of body fatness.Methods: This cross‐sectional sample included youth ages 10–23 years (67% female, 56% non‐black) with healthy weight (body mass index [BMI] = 5th–85th percentile, n = 236), obesity (BMI ≥ 95th percentile, n = 224) and type 2 diabetes (BMI ≥ 95th percentile, n = 145). Visceral fat was assessed via dual‐energy X‐ray absorptiometry. Carotid‐femoral pulse wave velocity (PWV) was assessed via applanation tonometry. Obesity and type 2 diabetes groups were combined for final analyses. Analyses accounted for age, sex, ancestry and mean arterial pressure.Results: Visceral fat and PWV were greater in youth with obesity versus healthy weight (p < 0.001). In youth with obesity, but not healthy weight, visceral fat was positively associated with PWV (p < 0.001) and was predictive of PWV beyond BMI and waist circumference.Conclusions: Visceral fat likely contributes to subclinical cardiovascular complications in youth. Since cardiovascular health tracks from adolescence to adulthood, longitudinal studies in youth with obesity are required to define the role of visceral fat in lifelong cardiovascular disease risk.

Context The ultradistal (UD) radius is rich in trabecular bone and is easily measured by dual energy X-ray absorptiometry (DXA). UD radius areal bone mineral density (aBMD) may help identify trabecular bone deficits, but reference data are needed for research and clinical interpretation of this measure. Objective We developed age-, sex-, and population ancestry-specific reference ranges for UD radius aBMD assessed by DXA and calculated Z-scores. We examined tracking of UD radius aBMD Z-scores over 6 years and determined associations between UD radius aBMD Z-scores and other bone measures by DXA and peripheral quantitative computed tomography. Design Multicenter longitudinal study. Participants A total of 2014 (922 males, 22% African American) children ages 5 to 19 years at enrollment who participated in the Bone Mineral Density in Childhood Study. Main Outcome Measure UD radius aBMD. Results UD radius aBMD increased nonlinearly with age (P < 0.001) and tended to be greater in males versus females (P = 0.054). Age-, sex-, and ancestry-specific UD radius aBMD reference curves were constructed. UD radius aBMD Z-scores positively associated with Z-scores at other skeletal sites (r = 0.54-0.64, all P < 0.001) and peripheral quantitative computed tomography measures of distal radius total volumetric BMD (r = 0.68, P < 0.001) and trabecular volumetric BMD (r = 0.70, P < 0.001), and was weakly associated with height Z-score (r = 0.09, P = 0.015). UD radius aBMD Z-scores tracked strongly over 6 years, regardless of pubertal stage (r = 0.66-0.69; all P < 0.05). Conclusion UD radius aBMD Z-scores strongly associated with distal radius trabecular bone density, with marginal confounding by stature. These reference data may provide a valuable resource for bone health assessment in children.

IGF‐I is a pivotal hormone in pediatric musculoskeletal development. Although recent data suggest that the role of IGF‐I in total body lean mass and total body bone mass accrual may be compromised in children with insulin resistance, cortical bone geometric outcomes have not been studied in this context. Therefore, we explored the influence of insulin resistance on the relationship between IGF‐I and cortical bone in children. A secondary aim was to examine the influence of insulin resistance on the lean mass‐dependent relationship between IGF‐I and cortical bone. Children were otherwise healthy, early adolescent black and white boys and girls (ages 9 to 13 years) and were classified as having high (n = 147) or normal (n = 168) insulin resistance based on the homeostasis model assessment of insulin resistance (HOMA‐IR). Cortical bone at the tibia diaphysis (66% site) and total body fat‐free soft tissue mass (FFST) were measured by peripheral quantitative computed tomography (pQCT) and dual‐energy X‐ray absorptiometry (DXA), respectively. IGF‐I, insulin, and glucose were measured in fasting sera and HOMA‐IR was calculated. Children with high HOMA‐IR had greater unadjusted IGF‐I (p < 0.001). HOMA‐IR was a negative predictor of cortical bone mineral content, cortical bone area (Ct.Ar), and polar strength strain index (pSSI; all p ≤ 0.01) after adjusting for race, sex, age, maturation, fat mass, and FFST. IGF‐I was a positive predictor of most musculoskeletal endpoints (all p < 0.05) after adjusting for race, sex, age, and maturation. However, these relationships were moderated by HOMA‐IR (p_Interaction < 0.05). FFST positively correlated with most cortical bone outcomes (all p < 0.05). Path analyses demonstrated a positive relationship between IGF‐I and Ct.Ar via FFST in the total cohort (β_{Indirect Effect}= 0.321, p < 0.001). However, this relationship was moderated in the children with high (β_{Indirect Effect}= 0.200, p < 0.001) versus normal (β_{Indirect Effect}= 0.408, p < 0.001) HOMA‐IR. These data implicate insulin resistance as a potential suppressor of IGF‐I‐dependent cortical bone development, though prospective studies are needed. © 2017 American Society for Bone and Mineral Research.

Purpose: To assess relationships between diet quality and areal bone mineral density (aBMD) in youth with healthy weight, obesity, and type 2 diabetes (T2D). Methods: We performed a secondary analysis of cross-sectional data from youth (55% African American, 70% female) ages 10–23 years with T2D (n = 90), obesity (BMI > 95th; n = 128), or healthy weight (BMI < 85th; n = 197). Whole body (less head) areal bone mineral density (aBMD) was assessed by dual-energy X-ray absorptiometry (DXA). aBMD was expressed as age-, sex-, and ancestry-specific standard deviation scores (Z-scores). Whole body aBMD Z-scores were adjusted for height-for-age Z-score. Diet was assessed via three-day diaries, and the Healthy Eating Index (HEI) was computed. Total HEI score and HEI subcomponent scores were compared across groups, and associations with aBMD Z-scores were assessed via linear regression adjusted for group, age, sex, and ancestry. Results: Mean HEI was similar between the healthy weight, obesity, and T2D groups. Several HEI sub-components differed between groups, including meats and beans, total vegetables, milk, saturated fat, sodium, oils, and empty calories. The obesity and T2D group had significantly greater aBMD Z-scores compared to the healthy weight group. Multiple linear regression analyses revealed a significant positive association between HEI and aBMD Z-score (p < 0.05). The HEI sub-components for whole grains (p = 0.052) and empty calories (p < 0.05) were positively associated with aBMD Z-score. Conclusions: Individuals that followed a dietary pattern more closely aligned with the Dietary Guidelines for Americans had greater bone density. Since few studies have investigated the role of diet on bone in youth with obesity-related conditions, additional research is required among these populations.