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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 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.

Childhood obesity rates in congenital adrenal hyperplasia (CAH) exceed the high rates seen in normal children, potentially increasing their risk of cardiovascular disease (CVD). Abdominal adiposity, in particular visceral adipose tissue (VAT), is strongly associated with metabolic syndrome and CVD. However, it remains unknown whether VAT is increased in CAH.The objective of the study was to determine whether adolescents and young adults with classical CAH have more VAT and sc adipose tissue (SAT) than matched controls and whether VAT and SAT are associated with biomarkers of metabolic syndrome, inflammation, and hyperandrogenism in CAH.This was a cross-sectional study at a tertiary center.CAH subjects (n = 28; 15.6 ± 3.2 y; 15 females) were matched for age, sex, ethnicity, and body mass index to healthy controls (n = 28; 16.7 ± 2.3 y; 15 females).VAT and SAT, using computed tomography imaging and serum biomarkers associated with CVD risk, were measured. Data are reported as mean ± SD.Both VAT (43.8 ± 45.5 cm(2)) and SAT (288.1 ± 206.5 cm(2)) were higher in CAH subjects than controls (VAT 26.4 ± 29.6 cm(2) and SAT 226.3 ± 157.5 cm(2); both P.001). The VAT to SAT ratio was also higher in CAH subjects (0.15 ± 0.07) than controls (0.12 ± 0.06; P.05). Within CAH, measures of obesity (waist to height ratio, fat mass) and inflammation (plasminogen activator inhibitor-1, high-sensitivity C-reactive protein, leptin) correlated strongly with VAT and SAT. In addition, homeostasis model assessment of insulin resistance, and low-density lipoprotein correlated with abdominal adiposity. There were no sex differences for VAT or SAT in CAH subjects.CAH adolescents and young adults have increased abdominal adiposity, with a higher proportion of proinflammatory VAT than SAT. An improved understanding of the mechanism of obesity in CAH may lead to targeted prevention and therapeutics in this high-risk population.

Clinicians caring for children rely on measures of linear growth as a biomarker of development and overall health. Current reference ranges for height velocity (HV) for US children are unable to provide HV percentiles or Z-scores for early maturing and late maturing children at ages other than age at peak velocity. We present empirically acquired, age-specific reference ranges for HV from a contemporary sample of US youth.Subjects were enrolled in the Bone Mineral Density in Childhood Study, a large, multicenter, multiethnic, contemporary cohort of children (aged 5-19 y at enrollment) from the United States followed for up to 7 years. More than 4000 annual (12 ± 1 mo) HV measurements from approximately 1500 children were available. Pubertal status was determined by breast stage or testicular volume assessed by experienced health providers. Age-specific reference ranges were determined using the LMS method.Reference ranges (third to 97th percentiles) were generated for the entire cohort and for subgroups whose pubertal timing was defined as "earlier," "average," or "later." African American girls experienced earlier pubertal onset and had greater HV at younger ages and lower HV at older ages, compared to non-African American girls; differences did not persist after adjustment for pubertal timing. These differences were not observed for males.These reference ranges for annual HV can be used to assess growth relative to peers of the same age and sex, with consideration of pubertal timing. Z-scores and exact percentiles for HV can also be determined for population studies.

Emerging evidence suggests a possible link between brown adipose tissue (BAT) and bone metabolism.The objective of this study was to examine the relationships between BAT and bone cross-sectional dimensions in children and adolescents.This was a cross-sectional study.The study was conducted at a pediatric referral center.Patients included 40 children and teenagers (21 males and 19 females) successfully treated for pediatric malignancies.There were no interventions.The volume of BAT was determined by fluorodeoxyglucose-positron emission tomography/computed tomography. Measures of the cross-sectional area and cortical bone area and measures of thigh musculature and sc fat were determined at the midshaft of the femur.Regardless of sex, there were significant correlations seen between BAT volume and the cross-sectional dimensions of the bone (r values between 0.68 and 0.77; all P ≤ 0 .001). Multiple regression analyses indicated that the volume of BAT predicted femoral cross-sectional area and cortical bone area, even after accounting for height, weight, and gender. The addition of muscle as an independent variable increased the predictive power of the model but significantly decreased the contribution of BAT.The volume of BAT is positively associated with the amount of bone and the cross-sectional size of the femur in children and adolescents. This relation between BAT and bone structure could, at least in part, be mediated by muscle.

Previous studies have demonstrated that increased muscle lipid content is associated with reduced muscle strength and physical performance, independent of muscle mass. An association between elevated muscle lipid content with skeletal muscle attenuation has been reported in a large number of studies. The relationship between vitamin D serum levels and muscle strength is well established. Patients with vitamin D deficiency have increased body fat and decreased muscle strength. A similar association between vitamin D levels and muscle strength has been reported both in the elderly and in healthy adolescent postmenarcheal girls. In several studies, skeletal muscle attenuation was demonstrated in vitamin D deficient patients with neuromuscular disorders. It is unclear whether vitamin D insufficiency is also related to adipose tissue infiltration in muscle. In the present study, the investigators hypothesized that there was an inverse relationship between serum vitamin D levels and adipose tissue infiltration in muscle, which is independent of muscle mass. This cross-sectional study tested this hypothesis by examining the relationship between serum 25-hydroxyvitamin D (25OHD) and skeletal muscle lipid content and muscle mass in a cohort of healthy young women. The study subjects were 90 postpubertal females, aged 16 to 22 years. Study outcome measures included anthropometric characteristics, serum 25OHD values determined with radioimmunoassay, and values of fat, muscle mass, and percent muscle fat determined using computed tomography (CT). The participants were divided into 2 groups based on baseline vitamin D levels: 41 % (n = 37) were 25OHD sufficient (≥30 ng/mL) and 59% (n = 53) were 25OHD insufficient (≤29 ng/mL); 24% of the latter were 25OHD deficient (≤20 ng/mL). The data demonstrated a strong inverse relationship between serum 25OHD levels and CT measurements of percent muscle fat (r = -0.37; P < 0.0003), whereas no such relationship was found between the 2 vitamin D groups for fat infiltration in the thigh muscle area (r = 0.16; P = 0.14). Multiple regression analysis showed that the association between 25OHD levels and percent muscle fat was independent of body mass or CT measures of subcutaneous and visceral fat. Compared with the vitamin D sufficient group, percent muscle fat was significantly higher in the vitamin D insufficient group (3.15 ± 1.4 vs. 3.90 ± 1.9; P = 0.038). These findings indicate that vitamin D insufficiency has an inverse association with fat infiltration in muscle, which is independent of body mass.

In children, bone mineral content (BMC) and bone mineral density (BMD) measurements by dual-energy x-ray absorptiometry (DXA) are affected by height status. No consensus exists on how to adjust BMC or BMD (BMC/BMD) measurements for short or tall stature.The aim of this study was to compare various methods to adjust BMC/BMD for height in healthy children.Data from the Bone Mineral Density in Childhood Study (BMDCS) were used to develop adjustment methods that were validated using an independent cross-sectional sample of healthy children from the Reference Data Project (RDP).We conducted the study in five clinical centers in the United States.We included 1546 BMDCS and 650 RDP participants (7 to 17 yr of age, 50% female).No interventions were used.We measured spine and whole body (WB) BMC and BMD Z-scores for age (BMC/BMD(age)), height age (BMC/BMD(height age)), height (BMC(height)), bone mineral apparent density (BMAD(age)), and height-for-age Z-score (HAZ) (BMC/BMD(haz)).Spine and WB BMC/BMD(age)Z and BMAD(age)Z were positively (P0.005; r = 0.11 to 0.64) associated with HAZ. Spine BMD(haz) and BMC(haz)Z were not associated with HAZ; WB BMC(haz)Z was modestly associated with HAZ (r = 0.14; P = 0.0003). All other adjustment methods were negatively associated with HAZ (P0.005; r = -0.20 to -0.34). The deviation between adjusted and BMC/BMD(age) Z-scores was associated with age for most measures (P0.005) except for BMC/BMD(haz).Most methods to adjust BMC/BMD Z-scores for height were biased by age and/or HAZ. Adjustments using HAZ were least biased relative to HAZ and age and can be used to evaluate the effect of short or tall stature on BMC/BMD Z-scores.

Context: Peripheral quantitative computed tomography (pQCT) measurements are frequently obtained to assess cancellous bone density in the appendicular skeleton. Large variations in bone morphology associated with skeletal development may limit the interpretation of pediatric pQCT studies based on a single slice. Objective: The objective of the study was to characterize the variability in trabecular bone density values along the length of the metaphysis. Design: The design was an analysis of pQCT bone density data. Setting: The study was conducted at a hospital radiology department. Patients: The study included 35 children with cerebral palsy aged 6–12 yr. Main Outcome Measure: Variations in cancellous bone density along the length of the proximal tibial metaphysis were measured. Results: The patterns of decay in metaphyseal trabecular bone density were different in all subjects, and the density changed from the physis to the shaft at a rate of 16.8 ± 8.2% per 1 mm (range 8.6–37.9% per 1 mm). The slopes of the density curve drastically changed in some children over a short period of 6 months. Even with a high correlation (r2 = 0.88) between the density of a slice located a fixed distance from the growth plate and the overall mean metaphysis density, the respective changes in density over 6 months were only moderately correlated (r2 = 0.58). Conclusions: These results underscore the difficulty in interpreting metaphyseal pQCT bone density measurements from a single slice and highlight the need for developing pQCT acquisition techniques that provide more representative bone density determinations in the appendicular skeleton of children.

Low bone mass may increase risk of fracture. Several chronic medical conditions, medications, and lifestyle factors affect bone mineral accrual. Appropriate reference values are essential for identification of children with bone deficits.Our objective was to establish reference curves for bone mineral content (BMC) and density (BMD) in children.The Bone Mineral Density in Childhood Study is an ongoing longitudinal study in which measurements are obtained annually at five clinical centers in the United States.Participants included 1554 healthy children (761 male, 793 female), ages 6-16 yr, of all ethnicities.Scans of the whole body, lumbar spine, hip, and forearm were obtained using dual-energy x-ray absorptiometry. Percentile curves based on three annual measurements were generated using the LMS statistical procedure.BMC of the whole body and lumbar spine and BMD of the whole body, lumbar spine, total hip, femoral neck, and forearm are given for specific percentiles by sex, age, and race (Black vs. non-Black). BMC and BMD were higher for Blacks at all skeletal sites (P0.0001). BMC and BMD increased with age, and a plateau was not evident by age 16 (girls) or age 17 (boys). The variation in BMC and BMD also increased with age.Age-, race-, and sex-specific reference curves can be used to help identify children with bone deficits and for monitoring changes in bone in response to chronic diseases or therapies.

The time of life in which peak bone mass in the axial skeleton is attained has been the subject of considerable controversy, with estimates ranging from the time of sexual and skeletal maturity to the fifth decade of life.The objective was to examine whether dual energy x-ray absorptiometry (DXA) and computed tomography (CT) values for bone mass and bone density (BD) in the axial skeleton increase after sexual and skeletal maturity.Measurements of vertebral bone mineral density and bone mineral content (BMC) by DXA and vertebral BD and BMC by CT were obtained in 50 sexually and skeletally mature white females at baseline and 3 yr later. CT BMC values were calculated through analysis of vertebral volume in relation to density (BMC = vertebral volume x BD).Although neither CT BD nor BMC measures changed with time, DXA bone mineral density and BMC values were significantly higher at follow-up (P0.0001). Despite strong correlations between DXA and CT bone measures, DXA yielded greater changes in bone values in 47 of 50 subjects.Bone acquisition in the lumbar spine as measured by CT reaches its peak by sexual and skeletal maturity. In contrast, bone values by DXA continue to increase after puberty and cessation of longitudinal growth. Increases in DXA measures are likely a reflection of inhomogeneous changes in soft tissues around the spine or of disproportionate increases in the posterior elements of the vertebrae rather than of changes within the vertebral body.

The effect that growth has on dual-energy x-ray absorptiometry (DXA) bone measurements is yet to be fully defined. The purpose of this study was to determine the best method for optimizing pediatric bone measurements using DXA. Height, weight, body mass index, skeletal age, and Tanner stage of sexual development were determined for 64 healthy boys and 60 healthy girls ages 6-17 yr. DXA of the lumbar vertebrae was performed to measure bone mineral content (BMC, grams) and areal bone mineral density (aBMD, grams per square centimeter), and geometric corrections were used to calculate volumetric bone mineral densities (vBMD): vBMD1 = aBMD/ radical(DXA-area) and vBMD2 = aBMD/bone height. Computed tomography (CT) imaging was performed to measure volumetric bone density (vBD) and vertebral volume (Vol) and to calculate CT-BMC = vBD * Vol. Linear regression was used to compare DXA-BMC vs. CT-BMC and CT vBD vs. DXA aBMD, vBMD1, and vBMD2. Multiple regression including the anthropometric and developmental parameters was also performed. DXA and CT BMC were highly correlated (r2= 0.94). However, DXA aBMD correlated more strongly with CT Vol (r2= 0.68) than with CT density (r2= 0.39), and calculation of DXA volumetric densities only slightly improved the density correlations (r2= 0.49 for vBMD1; r2= 0.55 for BMD2). The correlations for density were particularly poor for subjects in Tanner stages 1-3 (r2= 0.02 for aBMD; r2= 0.13 for vBMD1; r2= 0.27 for vBMD2). In contrast, multiple regression accounting for the anthropometric and developmental parameters greatly improved the agreement between the DXA and CT densities (r2= 0.91). These results suggest that DXA BMC is a more accurate and reliable measure than DXA BMD for assessing bone acquisition, particularly for prepubertal children and those in the early stages of sexual development. Use of DXA BMD would be reasonable if adjustments for body size, pubertal status, and skeletal maturity are made, but these additional assessments add significant complexity to the studies.

The amount of bone that is gained during adolescence is the main contributor to peak bone mass, which, in turn, is a major determinant of osteoporosis and fracture risk in the elderly. We examined whether computed tomography measurements for the density and the volume of bone in the axial and the appendicular skeletons could be tracked through puberty in 40 healthy white children (20 girls and 20 boys). Longitudinal measurements of the cross-sectional area and cancellous bone density of the vertebral bodies and the cross-sectional and cortical bone areas of the femurs at the beginning of puberty accounted for 62-92% of the variations seen at sexual maturity; on average, 3 yr later. When baseline values for these bone traits were divided into quartiles, a linear relation across Tanner stages of sexual development was observed for each quartile in both girls and boys. The regression lines differed among quartiles for each trait, paralleled each other, and did not overlap. Thus, we are now in a position to identify those children who are genetically prone to develop low values for peak bone mass and toward whom osteoporosis prevention trials should be geared.

The prevalence of osteoporosis and the incidence of fractures are substantially lower in black than in white subjects, a finding generally attributed to racial differences in adult bone mass. Whether these racial differences are present in childhood is the subject of considerable interest, as the amount of bone gained during growth is a major determinant of future susceptibility to fractures. We measured the density and size of the vertebrae and femurs of 80 black and 80 white healthy children, 8-18 yr of age, matched for age, gender, height, weight, and stage of sexual development, using computed tomography. Race had a significant and differential effect on the bones in the axial and appendicular skeletons. In the axial skeleton, black children had greater cancellous bone density, but similar cross-sectional area of the vertebral bodies. In contrast, in the appendicular skeleton, black children had greater femoral cross-sectional area, but similar cortical bone area and cortical bone density. Compared to white children, vertebral bone density and femoral cross-sectional area at sexual maturity were, on the average, 10.75% and 5.7% higher, respectively, in black children. Such significant variations may contribute to the racial differences in the prevalence of osteoporosis between black and white adults.

Recent observations suggest that throughout life the size of the vertebral bodies in females is smaller than that in males even after accounting for differences in body size. To confirm these reports and to determine whether similar differences exist in the appendicular skeleton, detailed measurements of the sizes of the vertebrae and the femur were obtained using computed tomography in 30 pairs of prepubertal boys and girls matched for age, height, and weight. Anthropometric parameters as well as gender influenced the cross-sectional area of the vertebrae. Heavier children had greater vertebral cross-sectional area than slender children regardless of gender, and the vertebral bodies were found to be significantly smaller in girls than in matched boys (approximately 11%), both using Student's t test (P < 0.0001) and its multivariate analog, the Hotelling's T2 test (P < 0.0001). In contrast to these findings in the axial skeleton, gender status did not influence the size of the bones in the appendicular skeleton, and neither the cross-sectional area (3.28 +/- 0.84 vs. 3.10 +/- 0.56 cm2) nor the cortical bone area (1.80 +/- 0.37 vs. 1.85 +/- 0.36 cm2) at the midshaft of the femur differed between boys and girls. These values, however, correlated strongly with all anthropometric indexes, and multiple regression analyses indicated that both measurements were primarily related to weight. The results suggest that although increases in mechanical loading associated with growth are the main determinant of the cross-sectional properties of the appendicular skeleton in children, factors other than body mass and related to gender have a significant role in the regulation of the sizes of the bones in the axial skeleton.

Osteoporosis is a disease characterized by the development of nontraumatic fractures, most commonly in the vertebrae of elderly women. Approximately 500,000 elderly women in the United States are newly diagnosed with vertebral fractures every year, as the compressive strength of the vertebra, mainly determined by the density of cancellous bone and its cross-sectional area, declines with age. A recent study in women suggested that a polymorphism in the Sp1 binding site of the collagen type I gene (COLIA1) was related to decreased vertebral bone mass and vertebral fractures. Determining the phenotypic trait(s) responsible for this relationship and whether this association is manifested in childhood would further define the structural basis for decreased bone mass and help identify children “at risk” for fractures later in life. We therefore studied the COLIA1 gene polymorphism and measurements of the size and the density of vertebral bone in 109 healthy, prepubertal girls. On average, 22 girls with the Ss genotype and one girl with the ss genotype had 6.7% and 49.4% lower cancellous bone density in the vertebrae than girls with the SS genotype. In contrast, there was no association between the size of the vertebrae and the COLIA1 genotypes.