Vertebral cross-sectional area: an orphan phenotype with potential implications for female spinal health.

A high priority in imaging-based research is the identification of the structural basis that confers greater risk for spinal disorders. New evidence indicates that factors related to sex influence the fetal development of the axial skeleton. Girls are born with smaller vertebral cross-sectional area compared to boys-a sexual dimorphism that is present throughout life and independent of body size. The smaller female vertebra is associated with greater flexibility of the spine that could represent the human adaptation to fetal load. It also likely contributes to the higher prevalence of spinal deformities, such as exaggerated lordosis and progressive scoliosis in adolescent girls when compared to boys, and to the greater susceptibility for spinal osteoporosis and vertebral fractures in elderly women than men.

Early injury to cortical and cancellous bone from induction chemotherapy for adolescents and young adults treated for acute lymphoblastic leukemia.

Diminished bone density and skeletal fractures are common morbidities during and following therapy for acute lymphoblastic leukemia (ALL). While cumulative doses of osteotoxic chemotherapy for ALL have been reported to adversely impact bone density, the timing of onset of this effect as well as other changes to bone structure is not well characterized. We therefore conducted a prospective cohort study in pre-adolescent and adolescent patients (10-21years) newly diagnosed with ALL (n=38) to explore leukemia-related changes to bone at diagnosis and the subsequent impact of the first phase of chemotherapy ("Induction"). Using quantitative computerized tomography (QCT), we found that pre-chemotherapy bone properties were similar to age- and sex-matched controls. Subsequently over the one month Induction period, however, cancellous volumetric bone mineral density (vBMD) decreased markedly (-26.8%, p<0.001) with sparing of cortical vBMD (tibia -0.0%, p=0.860, femur -0.7%, p=0.290). The tibia underwent significant cortical thinning (average cortical thickness-1.2%, p<0.001; cortical area-0.4%, p=0.014), while the femur was less affected. Areal BMD (aBMD) concurrently measured by dual-energy X-ray absorptiometry (DXA) underestimated changes from baseline as compared to vBMD. Biochemical evidence revealed prevalent Vitamin D insufficiency and a net resorptive state at start and end of Induction. Our findings demonstrate for the first time that significant alterations to cancellous and cortical bone develop during the first month of treatment, far earlier during ALL therapy than previously considered. Given that osteotoxic chemotherapy is integral to curative regimens for ALL, these results provide reason to re-evaluate traditional approaches toward chemotherapy-associated bone toxicity and highlight the urgent need for investigation into interventions to mitigate this common adverse effect.

Radiographic depiction of intra-abdominal fat in newborns: a marker of infants born to diabetic mothers.

OBJECTIVE: To examine whether the presence of intra-abdominal fat (IAF) in newborns is diagnostic of infants of diabetic mothers (IDMs), and determine whether IAF is merely the consequence of increased body size. STUDY DESIGN: Abdominal radiographs of 277 neonates >34 weeks gestational age (147 male and 130 female) were reviewed to determine the presence of IAF. Unpaired t-test and regression analyses were used to examine the influence of gestational age, birth weight, birth length and maternal diabetes on the prevalence and thickness of IAF. RESULT: The prevalence of IAF was higher in IDMs (41.2% vs 13.2%; P<0.0001)-an association that persisted even after accounting for sex, gestational age and weight. Both birth weight and maternal diabetic status influenced the amount of IAF. Values of IAF thickness in IDMs were, however, more than threefold greater than those in non-IDMs (2.53±2.08 vs 0.81±0.29 mm; P<0.0001). An IAF thickness >1.5 mm was indicative of an IDM. CONCLUSION: The depiction of IAF in radiographs is significantly more prevalent in IDMs when compared with non-IDMs, regardless of body size. A thickness of IAF >1.5 mm is a marker that should encourage work-up for the physiological, metabolic and congenital complications associated with IDM.

Anthropometric models of bone mineral content and areal bone mineral density based on the bone mineral density in childhood study.

UNLABELLED: New models describing anthropometrically adjusted normal values of bone mineral density and content in children have been created for the various measurement sites. The inclusion of multiple explanatory variables in the models provides the opportunity to calculate Z-scores that are adjusted with respect to the relevant anthropometric parameters. INTRODUCTION: Previous descriptions of children's bone mineral measurements by age have focused on segmenting diverse populations by race and sex without adjusting for anthropometric variables or have included the effects of a single anthropometric variable. METHODS: We applied multivariate semi-metric smoothing to the various pediatric bone-measurement sites using data from the Bone Mineral Density in Childhood Study to evaluate which of sex, race, age, height, weight, percent body fat, and sexual maturity explain variations in the population's bone mineral values. By balancing high adjusted R(2) values with clinical needs, two models are examined. RESULTS: At the spine, whole body, whole body sub head, total hip, hip neck, and forearm sites, models were created using sex, race, age, height, and weight as well as an additional set of models containing these anthropometric variables and percent body fat. For bone mineral density, weight is more important than percent body fat, which is more important than height. For bone mineral content, the order varied by site with body fat being the weakest component. Including more anthropometrics in the model reduces the overlap of the critical groups, identified as those individuals with a Z-score below -2, from the standard sex, race, and age model. CONCLUSIONS: If body fat is not available, the simpler model including height and weight should be used. The inclusion of multiple explanatory variables in the models provides the opportunity to calculate Z-scores that are adjusted with respect to the relevant anthropometric parameters.

Adiposity in children and adolescents: correlates and clinical consequences of fat stored in specific body depots.

The 2011 Pennington Biomedical Research Center's Scientific Symposium focused on adiposity in children and adolescents. The symposium was attended by 15 speakers and other invited experts. The specific objectives of the symposium were to (i) integrate the latest published and unpublished findings on the laboratory and clinical assessment of depot-specific adiposity in children and adolescents, (ii) understand the variation in depot-specific adiposity and related health outcomes associated with age, sex, maturation, ethnicity and other factors and (iii) identify opportunities for incorporating new markers of abdominal obesity into clinical practice guidelines for obesity in children and adolescents. This symposium provided an overview of important new advances in the field and identified directions for future research. The long-term goal of the symposium is to aid in the early identification of children and adolescents who are at increased health risk because of obesity and obesity-related conditions.

MRI-measured pelvic bone marrow adipose tissue is inversely related to DXA-measured bone mineral in younger and older adults.

BACKGROUND/OBJECTIVES: Recent research has shown an inverse relationship between bone marrow adipose tissue (BMAT) and bone mineral density (BMD). There is a lack of evidence at the macro-imaging level to establish whether increased BMAT is a cause or effect of bone loss. This cross-sectional study compared the BMAT and BMD relationship between a younger adult group at or approaching peak bone mass (PBM; age 18.0-39.9 years) and an older group with potential bone loss (PoBL; age 40.0-88.0 years). SUBJECTS/METHODS: Pelvic BMAT was evaluated in 560 healthy men and women with T1-weighted whole-body magnetic resonance imaging. BMD was measured using whole-body dual-energy X-ray absorptiometry. RESULTS: An inverse correlation was observed between pelvic BMAT and pelvic, total and spine BMD in the younger PBM group (r=-0.419 to -0.461, P<0.001) and in the older PoBL group (r=-0.405 to -0.500, P<0.001). After adjusting for age, sex, ethnicity, menopausal status, total body fat, skeletal muscle, subcutaneous and visceral adipose tissue, neither subject group (younger PBM vs older PoBL) nor its interaction with pelvic BMAT significantly contributed to the regression models with BMD as dependent variable and pelvic BMAT as independent variable (P=0.434-0.928). CONCLUSIONS: Our findings indicate that an inverse relationship between pelvic BMAT and BMD is present both in younger subjects who have not yet experienced bone loss and also in older subjects. These results provide support at the macro-imaging level for the hypothesis that low BMD may be a result of preferential differentiation of mesenchymal stem cells from osteoblasts to adipocytes.

Bone size and density measurements in prepubertal children with Turner syndrome prior to growth hormone therapy.

UNLABELLED: Using computed tomography (CT), we found the decreases in bone size of vertebrae and femur, cortical bone area (CBA) of femur and bone density (BD) of vertebrae in prepubertal female with Turner syndrome (TS) compared to those of controls. INTRODUCTION: Bone mineral density results from previous studies utilizing single-photon absorptiometry (SPA) or dual-energy X-ray absorptiometry (DXA) in children with TS are controversial. The present study used CT to assess the differences in cancellous and cortical bone size and BD between prepubertal TS patients prior to growth hormone therapy and historical age and ethnicity-matched female controls. METHODS: Anthropometrics and CT bone measurements including cross-sectional area (CSA) and BD of lumbar vertebrae and femur and CBA of femur in prepubertal TS females were reviewed and compared with those in controls. RESULTS: Twenty-two prepubertal TS patients had delayed bone age, were shorter and lighter than controls (Ps < 0.001). After adjusting for weight, height and skeletal age, vertebral BD and CBA of the femur were lower in patients than in controls (P < 0.001 and P = 0.021, respectively). However, after additional adjusting for puberty, results were not different from controls. While a positive correlation between vertebral BD and age was noted in controls (r = 0.367, P = 0.092), a significant negative correlation was noted in patients (r = -0.615, P = 0.002). CONCLUSIONS: While the decrease in vertebrae and femur sizes of patients with TS appeared to be secondary to their small body size, the decreased BD of vertebrae and CBA of femur were likely secondary to estrogen deficiency.

Fitting of bone mineral density with consideration of anthropometric parameters.

UNLABELLED: A new model describing normal values of bone mineral density in children has been evaluated, which includes not only the traditional parameters of age, gender, and race, but also weight, height, percent body fat, and sexual maturity. This model may constitute a better comparative norm for a specific child with given anthropometric values. INTRODUCTION: Previous descriptions of children's bone mineral density (BMD) by age have focused on segmenting diverse populations by race and gender without adjusting for anthropometric variables or have included the effects of anthropometric variables over a relatively homogeneous population. METHODS: Multivariate semi-metric smoothing (MS(2)) provides a way to describe a diverse population using a model that includes multiple effects and their interactions while producing a result that can be smoothed with respect to age in order to provide connected percentiles. We applied MS(2) to spine BMD data from the Bone Mineral Density in Childhood Study to evaluate which of gender, race, age, height, weight, percent body fat, and sexual maturity explain variations in the population's BMD values. By balancing high adjusted R (2) values and low mean square errors with clinical needs, a model using age, gender, race, weight, and percent body fat is proposed and examined. RESULTS: This model provides narrower distributions and slight shifts of BMD values compared to the traditional model, which includes only age, gender, and race. Thus, the proposed model might constitute a better comparative standard for a specific child with given anthropometric values and should be less dependent on the anthropometric characteristics of the cohort used to devise the model. CONCLUSIONS: The inclusion of multiple explanatory variables in the model, while creating smooth output curves, makes the MS(2) method attractive in modeling practically sized data sets. The clinical use of this model by the bone research community has yet to be fully established.

Differential effect of marrow adiposity and visceral and subcutaneous fat on cardiovascular risk in young, healthy adults.

BACKGROUND: Adipose tissue is an endocrine organ that influences many metabolic processes and accumulates in different depots, including the bone marrow. While the negative associations between visceral fat (VF) or subcutaneous fat (SF) and cardiovascular disease (CVD) risks are well known, the relation between marrow fat (MF) and metabolic risk is unexplored. OBJECTIVES: We examined the relations between these three fat depots and whether CVD risks are associated with marrow adiposity. DESIGN: Observational cross-sectional study. SUBJECTS AND METHODS: Computed tomography was used to measure VF, SF and MF depots in 131 healthy young adults (60 females, 71 males; 16-25 years of age). Weight, body mass index (BMI), waist and hip circumferences, blood pressure (BP), carotid intima-media thickness (CIMT) and serum levels of lipids, glucose and insulin were also measured. RESULTS: Regardless of gender, MF was not associated with values of VF or SF, anthropometric measures, or lipid or carbohydrate serum levels (P>0.05 for all). In contrast, VF was associated with SF (r values=0.74 for females, 0.78 for males; both P-values <0.0001) and these depots were related to anthropometric parameters (r values between 0.69 and 0.87; all P-values <0.0001) and to most measures of lipids, glucose or insulin (r values between 0.25 and 0.62). CONCLUSIONS: Marrow adiposity in young men and women is independent of VF and SF, and is not associated with CVD risk. These findings do not support the concept that marrow adiposity is involved in the comorbidities related to fat accumulation in other compartments.

Increased carotid artery intima-media thickness following venoarterial extracorporeal membrane oxygenation in the neonatal period.

OBJECTIVE: To compare left carotid intima-media thickness (CIMT) and biochemical markers for atherogenesis in neonatal venoarterial extracorporeal membrane oxygenation (ECMO) survivors with normal controls during childhood. METHODS: Venoarterial ECMO survivors and healthy patients between 12 and 18 years of age were enrolled in a matched control prospective study. ECMO survivors were matched to controls based on chronological age and percentage of body mass index (BMI). Measured CIMT of the posterior left carotid artery and CIMT values corrected for carotid artery size were used for data analysis. RESULTS: Thirty-one neonatal venoarterial ECMO survivors were matched to 31 healthy controls. No significant differences were found between ECMO survivors and controls for age, weight, percentage of BMI, total fat composition, lipid profiles, ultrasensitive C-reactive protein or homocysteine levels. Significant differences between ECMO and controls patients were found in systolic, diastolic and mean left CIMT. CONCLUSION: Compared with controls, the thickness of the left carotid intima media is significantly increased at the age of 12 to 18 years in neonatal venoarterial ECMO survivors. The clinical significance of this increased CIMT is unknown. ECMO centers may want to incorporate assessment of CIMT in their follow-up protocols.

Skeletal age determinations in children of European and African descent: applicability of the Greulich and Pyle standards.

This study assesses the value of the Greulich and Pyle method in determining the skeletal ages of healthy American children of European and African descent born after the year 1980. The hand and wrist radiographs of 534 children (265 boys, 269 girls; 260 European-Americans [EA], 274 African-Americans [AA]), ages 0 to 19 y, were analyzed by two experienced pediatric radiologists blinded to the chronological age of the subjects. A difference score was calculated for each subject by subtracting chronological age from the mean bone ages scores provided by the two raters. One group t-tests were performed to verify the hypothesis that the mean difference score was equal to zero. Skeletal age determinations by the two radiologists showed a high degree of agreement by intraclass correlation coefficient (r = 0.994). The range of values for differences in skeletal and chronological ages was very wide, indicating great individual variability. Comparisons between skeletal and chronological age only reached statistical significance in EA prepubertal girls, whose skeletal ages were delayed, on average, by three months (t = -2.9; p = 0.005). Mean difference between skeletal and chronological age in prepubertal children of African descent was 0.09 +/- 0.66 y, while that in children of European descent was -0.17 +/- 0.67 y; (t = 3.13; p = 0.0019). On average, the bone ages of 10% of all prepubertal AA children were 2 SD above the normative data in the Greulich and Pyle atlas, while the bone ages of 8% of all prepubertal EA children were 2 SD below. In contrast to the racial differences observed in prepubertal children, EA postpubertal males had significantly greater values for bone age than AA postpubertal males (t = 2.03; p = 0.05). In conclusion, variations in skeletal maturation in prepubertal children are greater than those reflected in the Greulich and Pyle atlas; prepubertal American children of European descent have significantly delayed skeletal maturation when compared with those of African descent; and, postpubertal EA males have significantly advanced skeletal maturation when compared with postpubertal AA males. New standards are needed to make clinical decisions that require reliable bone ages and to accurately represent a multiethnic pediatric population.

Computer-assisted bone age assessment: image preprocessing and epiphyseal/metaphyseal ROI extraction.

Clinical assessment of skeletal maturity is based on a visual comparison of a left-hand wrist radiograph with atlas patterns. Using a new digital hand atlas an image analysis methodology is being developed. To assist radiologists in bone age estimation. The analysis starts with a preprocessing function yielding epiphyseal/metaphyseal regions of interest (EMROIs). Then, these regions are subjected to a feature extraction function. Accuracy has been measured independently at three stages of the image analysis: detection of phalangeal tip, extraction of the EMROIs, and location of diameters and lower edge of the EMROIs. Extracted features describe the stage of skeletal development more objectively than visual comparison.

Increased body weight and decreased radial cross-sectional dimensions in girls with forearm fractures.

A large number of children sustain fractures after relatively minor trauma and several investigators have associated these fractures to a deficient accumulation of bone during growth. This study was conducted to better characterize the skeletal phenotype associated with low-energy impact fractures of the forearm in girls. The densities of cancellous, cortical, and integral bone and the cross-sectional area were measured in the radius of 100 healthy white girls (aged 4-15 years) using computed tomography (CT); 50 girls had never fractured and 50 girls had sustained a forearm fracture within the previous month. Fractured and nonfractured groups were matched for age, height, weight, and Tanner stage of sexual development. Compared with controls, girls with fractures had, on average, 8% smaller cross-sectional area at the distal radius (1.82 +/- 0.50 cm2 vs. 1.97 +/- 0.42 cm2; p < 0.0001) but similar cancellous, integral, and cortical bone densities. Neither radial length nor the amount of fat or muscle at the midshaft of the radius differed between girls with and without fractures. Both study subjects and matched controls were overweight. Although mean height was at the 50th percentile, mean weight was at the 90th percentile for age-adjusted normal values. Girls who sustain forearm fractures after minor trauma have small cross-sectional dimensions of the radius and tend to be overweight. The smaller cross-sectional area confers a biomechanical disadvantage that, coupled with the greater body weight, increases the vulnerability to fracture after a fall.

Computer automated approach to the extraction of epiphyseal regions in hand radiographs.

Epiphyseal region is the most sensitive region to developmental changes of the skeletal system. Extraction of this area is the very first step in any computerized image analysis. In this report a fully automated analysis of a hand radiograph resulting in extraction of distal and middle regions of the II, III, and IV phalanx is presented. The processing is performed in 3 stages. First, the trend of background is removed from radiograph to obtain a binary hand mask. At this stage a labeling procedure is necessary to eliminate artifacts (markers). Then, II, III, and IV phalanges are identified in the binary image, and the phalangeal axes are drawn. Finally, the intensity profile along each phalangeal axis is analyzed, and, on its basis, distal and middle regions are located. The presented procedure is designed as a part of currently developed system for automatic bone age assessment; however, it also can be as a preprocessing step in other diseases the diagnoses of which may require a computer assistance.

Early identification of children predisposed to low peak bone mass and osteoporosis later in life.

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.

Digital hand atlas and web-based bone age assessment: system design and implementation.

Bone age assessment is a procedure frequently performed in pediatric patients to evaluate their growth disorder. A simple method commonly used in bone age assessment is atlas matching by a radiological examination of a left-hand radiograph against a small reference set of Greulich-Pyle atlas patterns of normal standards. The method however can lead to significant deviation in age assessment, due to a variety of observers with different levels of training. The Greulich-Pyle atlas developed in the 1950s based on middle upper class white populations, is also not fully applicable for children of today, especially regarding the standard development in other racial groups. In this paper, we present our system design and initial implementation of a digital hand atlas and computer-aided diagnostic (CAD) system for Web-based bone age assessment. The CAD system is built on top of existing picture archiving and communication system (PACS), as well as recent advances in Internet technology. It consists of a hand atlas database, a CAD module and a Java-based Web user interface. The digital atlas is based on a large new set of clinically normal hand images of diverse ethnic groups. A relational image database system is used to organize hand images, their extracted quantitative features and patient data. The digital atlas removes the disadvantages of the currently out-of-date Greulich-Pyle atlas and allows the bone age assessment to be computerized. The Java-based Web user interface allows users to interact with the hand image database from browsers. Users can use a Web browser to push a clinical hand image to the CAD server for a bone age assessment. Quantitative features on the examined image, which reflect the skeletal maturity, are then extracted and compared with patterns from the atlas database to assess the bone age. The digital atlas method based on open system Internet technology provides an alternative to supplement or replace the traditional one for a quantitative, accurate and cost-effective assessment of bone age.

Evaluation of the effects of oxandrolone on malnourished HIV-positive pediatric patients.

OBJECTIVE: To determine the safety and efficacy of anabolic therapy to prevent or reverse wasting and malnutrition in human immunodeficiency virus (HIV)-infected pediatric patients. The anabolic steroid, oxandrolone, was evaluated because of its safe and effective use in other pediatric conditions. METHODS: Nine HIV-positive children who were malnourished or at risk for malnutrition (4 females, 5 males; 4-14 years of age) took oxandrolone for 3 months (.1 mg/kg/day orally). Quantitative HIV ribonucleic acid polymerase chain reaction and CD4(+) T-cell levels, complete blood cell count (CBC) and chemistry profile, endocrinologic studies, resting energy expenditure, respiratory quotient, nutritional measures, body composition assessment with quantitative computed tomography, and skinfold body composition measurements were determined before treatment, during treatment (3 months), and for 3 months after treatment. Statistical analyses were completed using the Friedman two-way analysis of variance and Spearman correlation tests. RESULTS: No adverse clinical or laboratory events or changes in Tanner staging or virilization occurred. Quantitative HIV ribonucleic acid polymerase chain reaction and CD4(+) T-cell levels did not change significantly. Insulin-like growth factor 1 increased, suggesting an anabolic effect of treatment. The rate of weight gain increased during treatment and was maintained after treatment. Linear growth continued and was maintained throughout treatment, whereas bone age did not increase significantly. Anthropometric assessments indicated an increase in muscle mass and a decrease in fat while patients were on treatment, and a mild decrease of muscle and increased fat posttreatment. Likewise, computed tomography scan results demonstrated similar changes in muscle mass. Resting energy expenditure and respiratory quotient remained stable throughout treatment and follow-up. No significant changes were seen in the quality of life questionnaire. CONCLUSIONS: Treatment with oxandrolone for 3 months in HIV-infected children was well-tolerated, safe, and associated with markers of anabolism. The latter effect was maintained partially for 3 months after discontinuation of a 3-month course of therapy. Additional studies are needed to assess the potential benefits and risks of a longer course of therapy or a higher dose of oxandrolone in HIV-infected children.

Biochemical markers of bone turnover and the volume and the density of bone in children at different stages of sexual development.

Bone mass and biochemical markers of bone turnover increase significantly during puberty. We studied the possible relationships between markers of bone formation and bone resorption and increases in skeletal size, bone volume, and bone density in healthy children at different stages of sexual development. Serum concentrations of bone specific alkaline phosphatase (BALP) and osteocalcin (bone Gla protein, BGP), urinary levels of pyridinoline (Pyr) and deoxypyridinoline (Dpyr) and computed tomography (CT) measurements of the cross-sectional areas of the vertebrae and the femurs, the apparent density of cancellous bone in the vertebrae, and the volume and the material density of cortical bone in the femurs were determined in 126 boys and 143 girls, ages 7-18 years. Serum levels of BALP and BGP and urinary concentrations of Pyr and Dpyr peaked in early puberty and were lowest in the later stages of puberty. CT measurements for the cross-sectional areas of the vertebrae and the femurs, the femoral cortical bone areas, and the apparent density of cancellous bone increased in all children during puberty, while values for material bone density did not change significantly with the stage of sexual development. BALP and BGP showed significant inverse correlations with the material density of bone (r = -0.23 and -0.24, respectively), but no association with bone volume in the appendicular or axial skeleton. In contrast, Pyr and Dpyr correlated with femoral cross-sectional area (r = -0.24 and -0.33, respectively) and cortical bone area (r = -0.29 and -0.33, respectively), and with the apparent density of vertebral cancellous bone (r = -0.26 and -0.19, respectively), but not with the material density of bone. We conclude that, during puberty, there is a differential association between the two components of bone mass and the markers of bone formation and bone resorption; while markers of bone formation are related to the material density of bone, markers of bone resorption are related to the volume of bone.

Serum levels of insulin-like growth factor I and the density, volume, and cross-sectional area of cortical bone in children.

Insulin-like growth factor I (IGF-I) is a major regulator of bone growth during childhood. However, beyond knowledge that IGF-I influences longitudinal growth, its associations to changes in the cross-sectional dimensions, the volume, or the material density of bone during growth are unknown. We assessed the relationships between serum IGF-I and measurements of cross-sectional area, cortical bone area, and cortical bone density at the midshaft of the femur in 197 normal healthy white children and adolescents (103 boys and 94 girls; aged 7.8-18.2 yr). Bone determinations were obtained using computed tomography, and levels of IGF-I were measured by RIA after an extraction procedure. IGF-I correlated significantly with both cross-sectional area (r = 0.49; P < 0.0001) and cortical bone area (r = 0.50; P < 0.0001), but did not correlate with the material density of cortical bone (r = -0.08). Multiple regression analyses showed that circulating levels of IGF-I were associated with cross-sectional area (P = 0.03) and cortical bone area (P = 0.04) values, even after correcting for the confounding effects of age, gender, weight, and femoral length. We conclude that IGF-I is a major determinant of the cross-sectional properties of bone, but does not influence the material density of bone, in the appendicular skeleton.