Interpretation of whole body dual energy X-ray absorptiometry measures in children: comparison with peripheral quantitative computed tomography
Introduction
The increase in bone strength throughout growth and development is the result of changes in bone geometry and bone mineral density (BMD) [30], [35]. As recently reviewed [30], BMD can be expressed within three different levels of biological organization. Material density (BMDmaterial) is the amount of mineral divided by the volume of the bone matrix, excluding marrow spaces, canals, and lacunae. Compartment density (BMDcompartment), also known as apparent density, is the amount of mineral divided by the volume of the trabecular or cortical compartment, including marrow spaces, canals, and lacunae. Total density (BMDtotal) is the amount of mineral divided by the volume enclosed by the periosteal bone surface.
Studies of bone mineral accretion in children should recognize the strengths and limitations of imaging techniques in characterizing changes in bone size and the different components of BMD during growth. BMDmaterial cannot be assessed with currently available noninvasive techniques. Trabecular and cortical BMDcompartment and BMDtotal can be measured with quantitative computed tomography (QCT) [30], [35]. Numerous recent QCT studies have been reported in the vertebrae [14], [15] and in long bones, such as the femur [14], [15], radius [25], [26], [29], [33], [34], and tibia [5], [24] in healthy children. These studies have characterized gender, maturation, and ethnic-specific differences in cortical dimensions, trabecular, and cortical BMDcompartment and BMDtotal.
QCT studies have yielded important insights into the distinct components of bone mineral accretion in children; however, dual energy X-ray absorptiometry (DXA) remains, by far, the most common and convenient method for the assessment of bone mass in research studies and in clinical applications in children and adults. Due to the inherent limitations of a two-dimensional projection technique, BMDcompartment and BMDtotal cannot be measured by DXA. Trabecular BMDcompartment cannot be measured by DXA due to inability to isolate the trabecular compartment from the surrounding cortical bone. Cortical BMDcompartment and BMDtotal cannot be measured by DXA due to inability to measure the cortical compartment volume and total bone volume, respectively. Geometric algorithms have been developed to estimate BMDtotal and cortical BMDcompartment in skeletal sites with relatively simple geometry [36]. For example, BMDtotal in the vertebrae may be estimated from the projected dimensions using formulas based on the assumption that the vertebrae represent an elliptical cylinder or cube [7], [19]. Similarly, BMDtotal and cortical BMDcompartment may be estimated in a discrete length of the femoral midshaft, assuming the shaft represents a hollow cylinder of constant cortical wall thickness [3], [36]. Unfortunately, these approaches care not readily applied to the complex shape of the whole skeleton and the biomechanical significance of BMC relative to bone area across the entire skeleton is not known.
Multiple sources of pediatric DXA reference data are now available for the calculation of whole body bone z scores (Table 1). These include gender-specific centile curves, age- and height-specific means and standard deviations, and z score prediction models [5], [10], [11], [18], [22], [23], [41]. Despite the recent widespread availability of whole body reference data, there is lack of consensus regarding the most appropriate strategy for the interpretation of two-dimensional whole body DXA BMC and bone area results across children of differing body size and body composition. Proposed strategies include assessing bone area relative to height and BMC relative to bone area [23], assessing BMC relative to height and age [10], or assessing BMC relative to body weight or lean mass [8], [16], [39]. No studies have compared these approaches to a three-dimensional imaging technique.
Cortical bone composes 80% of the skeletal bone mass; therefore, whole body DXA BMC and area reflect predominantly cortical bone mass and dimensions. The primary function of cortical bone is mechanical strength. We hypothesize that measures of DXA whole body BMC and bone area relative to height will correlate with bone strength, while DXA whole body BMC and bone area relative to body weight and BMC relative to bone area will provide poor estimates of bone strength.
The objective of this study was to develop analytic strategies for the assessment of whole body DXA that describe the biomechanical characteristics of cortical bone across a wide range of body sizes. Peripheral QCT measures of stress-strain index (SSI) in the tibia will be used as the gold standard measure of bone strength. SSI incorporates cortical BMDcompartment and cortical endosteal and periosteal dimensions in a summary measure of strength that has been validated in human cadaver studies and animal studies [1], [12]. The comparison of DXA measures with peripheral quantitative computed tomography (pQCT) will provide a criterion for identifying the optimal approach for interpreting whole body DXA scans as measures of cortical bone strength in children.
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Study subjects
Children and adolescents, ages 6–21 years, were enrolled as healthy controls for ongoing bone studies in the Nutrition and Growth Laboratory at the Children's Hospital of Philadelphia (CHOP). Subjects were recruited from the CHOP general pediatric clinics, as well as from the surrounding community using newspaper advertisements and flyers. Subjects with chronic medical conditions or medications possibly affecting growth, pubertal development, nutritional status, or dietary intake were excluded.
Subject characteristics
A total of 150 healthy children and adolescents (75 female), 6–21 years of age, were enrolled. The females were older than the males (females 13.4 ± 3.1, males 11.6 ± 3.5; P < 0.01) and were more mature (P < 0.01). The subjects were similar in height to the national reference data. The mean weight and BMI z scores were significantly greater than zero, consistent with the high prevalence of overweight in the general population. The subject characteristics are summarized in Table 2.
DXA and pQCT results
The DXA and
Discussion
The new data presented here demonstrated that whole body DXA measures of bone area for height and BMC for height provide the best estimates of cortical bone dimensions and strength in males and females across a broad range of body sizes. These measures provide better estimates of bone strength than measures expressed relative to age. Furthermore, DXA whole body BMC for bone area was weakly correlated with bone strength in females, and no correlation was observed in males.
Cortical bone fulfills
Acknowledgements
We greatly appreciate the dedication and enthusiasm of the children and their families who participated in this study. Special thanks to Margarita Gomelsky, Susan Kaup, and the staff of the General Clinical Research Center for their efforts collecting these data. This protocol was supported by NIH grants K08-DK02523 (MBL) and 1-R03-DK058200 (MBL), the General Clinical Research Center (M01RR00240), and the Nutrition Center, The Children's Hospital of Philadelphia.
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