The Effect of Weight Change on Total Body Dual-Energy X-ray Absorptiometry: Results from a Clinical Trial

In the past decade dual-energy X-ray absorptiometry (DXA) scanning has assumed an important role in the evaluation of new treatments for osteoporosis. Although the spine and hip are the sites usually chosen for monitoring bone mineral density (BMD) changes, total body DXA is also of interest because of the comprehensive view it gives of the whole skeleton. However, recent studies have reported anomalies in total body DXA in subjects undergoing weight change, suggesting that the technique may not be valid in this circumstance. The present study evaluated total body DXA in a trial of cyclical etidronate therapy in which many subjects underwent significant weight change. The study population was 152 postmenopausal women who had spine, hip and total body DXA scans performed at baseline, 1 and 2 years. The total body scans were analyzed using two software options referred to as “standard” and “enhanced”. The following variables were studied: total body BMD, total body bone mineral content (BMC), and subregional BMD values for the following seven sites: lumbar spine, thoracic spine, pelvis, head, ribs, arms and legs. The percentage change from baseline was analyzed in a multivariate regression analysis to derive the treatment effect (defined as the difference in changes between the etidronate and placebo groups) and a coefficient that described the effect of weight change on the total body DXA variable. Mean weight change after 2 years was +1.1 kg (range −9.3 to +16.8 kg). Results for the weight change coefficient were significantly different from zero for five of nine total body variables using the standard analysis and seven of nine for the enhanced analysis with values (and standard errors) that varied from +0.67 (0.04) %/kg for standard total body BMC to −0.32 (0.11) %/kg for enhanced arm BMD. Results for the treatment effect at 2 years were significantly different from zero for total body BMD, total body BMC and for the lumbar spine, thoracic spine and pelvis BMD subregions, but were not significant for head, rib, arm or leg BMD. Findings for the standard and enhanced analyses agreed closely and the size of the treatment effect was related to the proportion of trabecular bone at the measurement site. We conclude that in a randomized study the effects of weight change can be corrected and total body DXA can give useful information about the response to treatment across the whole skeleton. Received: 18 February 2000 / Accepted: 12 April 2000     

Utility of Heel Dual-Energy X-ray Absorptiometry in Diagnosing Osteoporosis

Although peripheral dual-energy X-ray absorptiometry measurements have been found to predict fractures in population studies of white subjects, little is known about their utility in other races and in patients with greater risk of fracture. In a cross-sectional study of 874 women referred for bone mineral density (BMD) testing, we examined the utility of heel BMD in African-American (AA) compared with Caucasian (CA) women and in women using glucocorticoids. The ability of heel T-score to predict central osteoporosis was similar in AA and CA women (odds ratio [OR] per 1 unit decrease in T-score of 2.79 [95% confidence interval {CI} 2.16–3.60] and 3.15 [95% CI 2.53–3.92], respectively). The association between heel T-score and prevalent vertebral fractures was also similar in the 2 groups (OR 1.46 [95% CI 1.15–1.85] in AA and 1.42 [95% CI 1.16–1.74] in CA). In women using glucocorticoids heel T-score was better than central T-score in predicting vertebral fractures (OR 1.38 [95% CI 1.03–1.85] and 1.22 [95% CI 0.86–1.73], respectively). We conclude that in a multiracial referral population heel BMD predicts central osteoporosis and prevalent vertebral fractures equally well in AA as in CA women and may be better than central BMD in assessing fragility in glucocorticoid users.     

Dual-Energy X-ray Absorptiometry Predictors of Vertebral Deformities in Beta-Thalassemia Major

Vertebral fractures in beta-thalassemia major are increasingly found because of the longer life expectancy of patients, with a major negative impact on their quality of life. We performed a retrospective cross-sectional study to investigate the prevalence of vertebral deformities in thalassemic patients and to identify their best dual-energy X-ray absorptiometry (DXA) predictor among trabecular bone score (TBS), bone mineral density (BMD), and Z-score. Eighty-two outpatients with beta-thalassemia major on regular conventional treatment were studied at a single academic center. All patients underwent plain thoracic-lumbar spine X-rays and lumbar DXA to assess the number and the severity of vertebral deformities (Genant's method), the spinal deformity index, lumbar spine DXA parameters (BMD, TBS, and Z-score), and the presence of platyspondyly. Twenty-nine patients (35%) had vertebral deformities and showed significantly lower TBSs than the remainders (1.141?±?0.083 vs 1.254?±?0.072, p?<?0.0001). The analysis of variance of the TBS between the group of patients without vertebral deformities (spinal deformity index?=?0) and the remaining groups showed a significant difference (p?<?0.001). The TBS had better sensitivity (86.2%), specificity (75.5%), and diagnostic accuracy (79.3%) than BMD and Z-score in discriminating patients with and without vertebral deformities. Combining the TBS with the BMD or the Z-score showed that the diagnostic accuracy of the first in discriminating patients with and without vertebral deformities improved from 79.3% to 85.4% and 87.8%, respectively. The presence of platyspondyly was a significant predictor of vertebral deformities in the multivariate model. Vertebral deformities in well-treated patients with beta-thalassemia major are common and are often unrecognized. In our hands, the TBS was better than the BMD and the Z-score in predicting vertebral deformities. Plain X-rays of the spine should be performed also in asymptomatic patients, especially when the TBS is low.     

A Comparative Study of Computed Digital Absorptiometry and Conventional Dual-Energy X-ray Absorptiometry in Postmenopausal Women

The aim of the study was to evaluate whether computed digital absorptiometry (CDA) of the hand might be a useful screening technique for identifying patients with postmenopausal osteoporosis and to compare the results of CDA with those of dual-energy X-ray absorptiometry (DXA) of the lumbar spine and femoral neck. We studied 230 postmenopausal women (mean age 58.4 ± 7.9 years). For CDA, bone mineral density (BMD) was measured with an AccuDEXA Schick densitometer in the third middle phalanx of the nondominant hand. For DXA, BMD of the lumbar spine and upper femur was assessed using a DXA Hologic QDR-1000 densitometer. We did a comparative analysis (ANOVA) and linear correlation tests. Sensitivity and specificity of CDA and receiver operating characteristic (ROC) curves for the diagnosis of osteoporosis were calculated. The mean BMD with CDA was 0.445 ± 0.084 (T-score: −1.27 ± 1.29). The mean BMD (g/cm²) with DXA at the lumbar spine was 0.877 ± 0.166 (T-score: −1.52 ± 1.59) and 0.708 ± 0.127 at the femoral neck (T-score: −1.12 ± 1.25). BMD at the lumbar spine and femoral neck correlated positively with CDA of the hand (r= 0.66 and r= 0.65 respectively, p<0.001). When using as cut-off a T-score of −2.5, according to WHO criteria, 76 women (33%) had osteoporosis of the lumbar spine and/or femoral neck with DXA and 42 (18%) with CDA (p<0.001). The kappa score for osteoporosis was 0.33 for CDA versus spinal DXA and 0.35 for CDA versus femoral DXA. With the cut-off level used, sensitivity and specificity of CDA in detecting osteoporosis at the lumbar spine were 0.39 and 0.90, respectively; sensitivity and specificity of CDA in identifying osteoporosis at the femoral neck were 0.58 and 0.87, respectively. The positive predictive value of CDA for osteoporosis was 69% and the negative predictive value was 75%. The area under the ROC curve for osteoporosis was 0.822 ± 0.028. We conclude that: (a) CDA assessment has a moderate correlation with BMD measured by DXA at the lumbar spine and femoral neck; (b) CDA has a low sensitivity for the diagnosis of osteoporosis compared with spinal and femoral DXA; and (c) predictive values for osteoporosis at both the lumbar spine and femoral neck are acceptable. Received: September 2000 / Accepted: January 2001     

Bone Density Measured by Dual-Energy X-ray Absorptiometry in Healthy Kuwaiti Women

A preliminary cross-sectional study of 623 healthy Kuwaiti women aged 20-79 years was carried out using dual-energy X-ray absorptiometry (DXA) to establish reference values of bone mineral density (BMD). Measurements were taken at the lumbar spine and proximal femur. The data were compared with normative data taken from Caucasian U.S./North European women over 6 decades of age. Our results showed the expected decline in BMD with age, especially for postmenopausal women. Despite differences in ethnicity, diet, and lifestyle no statistically significant differences in BMD were detected between the Kuwaiti subjects and the Caucasian normative data. Age-matched, clinically well-defined normative data for a given population must be used to diagnose osteoporosis and establish fracture risk. This study represents baseline data for Kuwaiti Arab females: it indicates that their BMD values are close to those of Caucasian females and higher than those reported recently for Lebanese and Saudi females. Further data is being collected to increase the statistical power of the study.     

Dual-Energy X-ray Absorptiometry Diagnostic Discordance Between Z-Scores and T-Scores in Young Adults

Diagnostic criteria for postmenopausal osteoporosis using central dual-energy X-ray absorptiometry (DXA) T-scores have been widely accepted. The validity of these criteria for other populations, including premenopausal women and young men, has not been established. The International Society for Clinical Densitometry (ISCD) recommends using DXA Z-scores, not T-scores, for diagnosis in premenopausal women and men aged 20–49 yr, though studies supporting this position have not been published. We examined diagnostic agreement between DXA-generated T-scores and Z-scores in a cohort of men and women aged 20–49 yr, using 1994 World Health Organization and 2005 ISCD DXA criteria. Four thousand two hundred and seventy-five unique subjects were available for analysis. The agreement between DXA T-scores and Z-scores was moderate (Cohen's kappa: 0.53–0.75). The use of Z-scores resulted in significantly fewer (McNemar's p < 0.001) subjects diagnosed with “osteopenia,” “low bone mass for age,” or “osteoporosis.” Thirty-nine percent of Hologic (Hologic, Inc., Bedford, MA) subjects and 30% of Lunar (GE Lunar, GE Madison, WI) subjects diagnosed with “osteoporosis” by T-score were reclassified as either “normal” or “osteopenia” when their Z-score was used. Substitution of DXA Z-scores for T-scores results in significant diagnostic disagreement and significantly fewer persons being diagnosed with low bone mineral density.     

Body Composition by Dual-Energy X-ray Absorptiometry in Black Compared with White Women

Dual-energy X-ray absorptiometry (DXA) has recently been applied to the measurement of body composition using a three-compartment model consisting of fat, lean and bone mineral. The mass of skeletal muscle may be approximated by measurement of the lean tissue mass of the extremities. In addition, body fat distribution can be estimated by determining the ratio of fat in the trunk to the fat in the extremities. In the current study, DXA was used to compare body composition and fat distribution between black (n= 162) and white women (n= 203). Black women had a higher mineral mass and a higher skeletal muscle mass. The ratio of mineral to muscle mass was higher in black women, even when the data were adjusted for age, height and weight. Both total body bone mineral and muscle mass declined with age in both races, with evidence for an accelerated loss of bone mineral after menopause. Body size (height and weight) was generally a significant variable in developing regressions of each compartment against age. Their higher musculoskeletal mass may lead to misclassification of 12% of black women as obese if body mass index is used as an index of obesity. Body fat distribution (trunk/leg) did not differ between races in the raw data. However, for women of the same age, height and weight, white women have a significantly higher trunk/leg fat ratio. Body composition values for fat, lean and bone mineral obtained from DXA should be adjusted not only for gender but also for age, height, weight and ethnicity. Received: 23 September 1998 / Accepted: 4 January 1999     

Precision and Accuracy of a Transportable Dual-Energy X-ray Absorptiometry Unit for Bone Mineral Measurements in Guinea Pigs

Dual energy X-ray absorptiometry (DXA) is a valuable tool for measuring bone mineral content (BMC) and bone mineral density (BMD) in small-animal research. The present study was devised to establish guidelines and to define sites for bone mineral measurements in guinea pigs and to evaluate the accuracy of a new transportable research DXA unit. Repeated scans were performed on 30 guinea pig hindlimbs (in situ) as well as the isolated bones from these limbs (ex situ). Nine exactly specified regions of interest (ROIs) were analyzed twice for BMC and BMD by three different observers. Additionally, the BMC of whole bones and bone segments as measured by DXA was correlated to ash weights of bone in a subset of five animals to determine the accuracy of the DXA measurements. On ex situ scans, intra-observer variability for BMD ranged from 0.09% to 2.33% and inter-observer variability from 0.23% to 5.86% depending on the site studied, with smaller ROIs exhibiting more variability. Coefficients of variance (CV) for BMC measurements were slightly higher than for BMD. However, BMC offered a better correlation between in situ and ex situ values than BMD. On in situ scans, observer variability for BMD and BMC for comparable sites was higher than the ex situ variability. The results of this study indicate that DXA provides an accurate measurement of BMC even in small specimens. The precision of BMC and BMD measurements in situ can be improved considerably by using specific, well-defined ROIs and by careful placement of the bones to be scanned in close proximity to the scanning surface.     

Dual-Energy X-ray Absorptiometry Assessment of Tibial Mid-third Bone Mineral Density in Young Athletes

We suggested a new reproducible method to measure densitometric values at mid-third part of the tibia by dual-energy X-ray absorptiometry (DXA; Delphi, Hologic^®, Waltham, MA) in a population of young adults. Our population was composed of 170 subjects aged 22.7 ± 4.0 yr: athlete men (n = 67) and women (n = 40); control men (n = 33) and women (n = 30). Athletes practiced collective sports, judo or weightlifting for 10.0 ± 3.6 h/wk. We measured bone area (cm²), bone mineral content (BMC, g), and bone mineral density (BMD,g/cm²) at the left total hip and the mid-third part of the tibia with DXA. For the tibia scan, we used the whole body mode. To ensure the reproducibility of the method, both legs were extended and the feet were maintained on a support in an internal rotation of 35°. The region of interest of the lumbar spine from the whole body scan was positioned around the mid-third part of the tibia. Area, BMC, and BMD values were significantly higher in athletes compared with those of controls. The intra- and interobserver variability of the image analysis were 0.38% and 1.01%, respectively. For BMD measurements, the short-term (4 scans/d) and mid-term (4 scans/mo) reproducibility were 1.33% and 1.94%, respectively. DXA is a suitable tool to evaluate densitometric measurements at the mid-third part of the tibia and the influence of physical activity on that bone site.     

Bone Mineral Density Measured by a Portable X-ray Device Agrees With Dual-Energy X-ray Absorptiometry at Forearm in Preschool Aged Children

Dual-energy X-ray absorptiometry (DXA) measures of bone mineral density (BMD) are generally not feasible in fieldwork. The present study determined the agreement between BMD measured by DXA and portable peripheral DXA in preschool aged children. Fifty-seven children (4.2 ± 1.0 yr) had their nondominant distal forearm scanned using a peripheral DXA scanner (PIXI; GE Medical Systems Lunar, Madison, WI) at their daycare and a DXA (4500A Discovery Series; Hologic Inc., Bedford, MA) at our research clinic. Correlation analysis, one-way analysis of variance, and Bland-Altman plots were performed to examine the agreement between measurements. Data were also divided into tertiles for cross-classification analysis and calculation of kappa coefficients. Distal forearm BMD measured by PIXI was significantly correlated with DXA measures of total forearm BMD (r > 0.51; p < 0.001), proximal 1/3 BMD (r > 0.41; p < 0.001), mid-BMD (r > 0.37; p < 0.001), and ultradistal (UD) BMD (r > 0.57; p < 0.001). Cross-classification in the same or adjacent tertile between measures (UD forearm: 96.5%; UD radius: 94.4%; total forearm: 87.7%; total radius: 84.2%) resulted in weighted kappa coefficients of 0.46, 0.58, 0.42, and 0.43, respectively. Bland-Altman plots further clarified these agreements as all had low bias (UD forearm: bias = 0.003 ± 0.002; UD radius: ?0.015 ± 0.021; total forearm: ?0.062 ± 0.027; total radius: ?0.077 ± 0.026). These results demonstrate that portable DXA measures of forearm BMD agree moderately with DXA.     

Radiolucent Casting Tape Allows for Accurate Measurement of Forearm Bone Mineral Density Using Dual-Energy X-ray Absorptiometry

The ability to perform dual-energy X-ray absorptiometry (DXA) while a patient is in a cast would give investigators the opportunity to follow early changes in bone mineral density (BMD, g/cm2) during fracture healing or to evaluate bone changes related to immobilization. The objective of this study was to determine if accurate and precise DXA scans could be obtained through polyester-based radiolucent casting tape (Delta-Cast Elite [DCE], Johnson & Johnson, Inc., Raynham, MA) and standard fiberglass casting tape (Delta Lite [DL], Johnson & Johnson, Inc.). DXA scans were performed using a Lunar DPXL densitometer. Standard forearm regions of interest were analyzed. Ten normal volunteers had three consecutive scans of their dominant arm with no cast, with a radiolucent (DCE) cast, and with a fiberglass (DL) cast. Precision was calculated using data from three volunteers (three scans each; no cast, DCE, DL). Results of DCE and DL were compared with results with no cast. In a second series, a spine phantom was placed inside rice-filled forearm casts and repetitively scanned; results with DCE and DL were compared with the mean BMD values for the phantom alone. Analyses of the scans through the DL casts were difficult because the radiodensity of the fiberglass interfered with edge detection. This problem was exacerbated by low BMD (i.e., scans for women). Edge detection was not a problem with the DCE scans. Although the group mean BMD values with in vivo no cast, DCE, or DL scans were similar for all regions of interest, the data obtained for ultradistal regions of interest with DL scans were less precise. BMD values for the fiberglass-encased phantom were significantly lower compared with no cast or DCE scans (p = 0.0002). This study demonstrates that it is possible to perform accurate and precise forearm DXA scans through polyester-based radiolucent DCE casting tape.     

Quantitative Ultrasound and Dual-Energy X-ray Absorptiometry in Children and Adolescents With Neurofibromatosis of Type 1

Reduced areal bone mineral density (aBMD) is a common feature of neurofibromatosis type 1 (NF1). Moreover, in recent years there has been a growing interest in using quantitative ultrasound (QUS) for the evaluation of bone status. In 55 NF1 subjects (mean age: 9.3 ± 5.4 yr) and in 51 age- and sex-matched controls we measured aBMD at lumbar spine, at femoral neck (aBMD-FN), and at total femur (aBMD-T). Apparent volumetric bone mineral density (BMAD) was also calculated. In all subjects, QUS parameters at phalanges were evaluated. In NF1 subjects, the values of aBMD and BMAD were lower than in controls at all skeletal sites, but the difference reached statistical significance only at femoral sites (p < 0.05). Both aBMD and QUS parameters were lower in those NF1 subjects with skeletal abnormalities than in those without abnormalities, but the difference was statistically significant (p < 0.05) only for aBMD-FN and aBMD-T. Multiple regression analysis showed that the subjects with skeletal abnormalities had a higher risk of having bone transmission time (BTT) Z-score and aBMD Z-score at femoral sites less than ?1. In conclusion, our results suggest that aBMD and QUS represent useful tools in evaluating the impairment of bone status in NF1 subjects.     

Yield Point in Prediction of Compressive Behavior of Lumbar Vertebral Body by Dual-Energy X-ray Absorptiometry

The aims of the present study were to evaluate the influence of bone mineral content (BMC) and density on the behavior of the lumbar vertebra during compression and to determine critical points during compression. Dual-energy X-ray absorptiometry (DXA) and compression tests were performed on 44 vertebral bodies obtained from 22 cadavers. The results of the study indicate that bone mineral content measured by DXA were strongly correlated with ultimate failure load (r = 0.53, p < 0.001), ultimate failure stress (r = 0.581, p < 0.001), and toughness (r = 0.632, p < 0.001). Correlation with the yield point (r = 0.543, p < 0.001) was also significant. Bone mineral density showed similar results with ultimate failure load (r = 0.742, p < 0.001), ultimate failure stress (r = 0.742, p = 0.001), toughness (r = 0.673, p < 0.001), and yield point (r = 0.693, p < 0.001). The correlation between elastic parameters and DXA were suggestive but not quite significant. BMC was not related significantly with stiffness or Young's modulus. There was no correlation between bone mass and vertebral deformation parameters. In conclusion, bone mass and bone density appear to have a clear relationship to ultimate parameters and yield point. The relation with the yield point might be critical because it marks the beginning of the plastic region and signals the appearance of the first trabecular fractures.     

Usefulness of Reflection Scanning in Determining Whole-Body Composition in Broadly Built Individuals Using Dual-Energy X-ray Absorptiometry

Whole-body composition analysis by dual-energy X-ray absorptiometry (DXA) requires subjects to fit within the width limits of the DXA bed. To overcome this limitation, the aim of this study was to validate a partial scanning technique at which the upper left limb is deliberately left unscanned and measurements are “reflected” from the right-side upper limb. A Hologic Explorer-W densitometer was used in a sample of 189 participants, including athletes and nonathletes, ranging from underweight to obese (body mass index: 17.0–40.1 kg/m²). A whole-body scan was analyzed as the reference procedure to determine bone mineral content (BMC), lean soft tissue (LST), and fat mass (FM), and reanalyzed using a partial reflection scanning (RS) technique. RS estimates of BMC were associated with athletic status and differed significantly from reference estimates (p < 0.05). Also, the RS estimates of LST and FM were different (p < 0.05) from those of the reference whole-body scan, although differences were small (0.17 kg, ?0.02 kg, and ?0.10% for BMC, LST, and FM, respectively). The alternative procedure explained more than 99% of the reference scan variance with low limits of agreement (BMC: ?13.8 to 23.9 g [athletes] and ?6.3 to 18.0 g [nonathletes]; LST: ?0.11 to 0.45 kg; FM: ?0.22 to 0.17 kg). Regardless of body mass index, athletic status, and gender, RS is a useful and simple solution to be used in individuals wider than the DXA scan area. However, individual errors for BMC may be higher in athletes engaged in lateral dominant sports practice.     

Anomalies in the Measurement of Changes in Bone Mineral Density of the Spine by Dual-Energy X-ray Absorptiometry

Dual-energy X-ray absorptiometry (DXA) is frequently used for longitudinal studies of bone mineral status because of the high precision obtained, but evidence is emerging that the accuracy of measurements of changes may be a limitation because of artefacts of the analysis procedure, in particular, a dependence of the measured bone area (BA) on the bone mineral content (BMC). Results of spine bone mineral measurements taken at intervals with two DXA scanners, a Hologic QDR 1000W, and a Norland XR 26 HS, were examined. There was a consistent correlation between changes in BA and in BMC, with a slope of approximately 0.25 when expressed as percentages. A real change of BA of the magnitude observed is not feasible. There were no differences among the correlations for different instruments, genders, ages, or weight changes. There would appear to be an underestimation of changes in bone mineral density (BMD), but there is a possibility that some of the anomaly is manifested as an overestimation of a change in BMC. Phantom measurements were undertaken with the DXA scanners mentioned above and with a Lunar DPX. The phantoms consisted of simulations of the spine cut from aluminium sheet, so that the effective BMD could be varied. The dependence of the measured BA on BMC varied with the phantom outline, particularly the thickness of the transverse processes. Evidence was obtained of both an underestimate of BMD changes and an overestimate of BMC changes. There are errors in measuring spine changes, but these do not seem to be as serious as a previous report suggests for the Hologic scanner and are not likely to lead to misinterpretation of results. Received: 17 June 1997 / Accepted: 23 January 1998     

The Contribution of Cortical and Cancellous Bone to Dual-Energy X-ray Absorptiometry Measurements in the Female Proximal Femur

Dual-energy X-ray absorptiometry (DXA) is the most common method for determining bone mineral density (BMD) in the proximal femur. However, there remain questions concerning the contribution of cortical and cancellous bone to this technology in the proximal femur. The purpose of this investigation was to identify structural and compositional characteristics of human bone in the proximal femur that significantly influence DXA BMD measurements. Twenty-four femora were obtained at autopsy from Caucasian females ranging in age from 17 to 92 years (mean ± SD, 61 ± 25 years). DXA scans were performed on each specimen with a Hologic QDR-2000 densitometer. Direct measurements were determined from proximal femoral sections for cancellous bone (volume fraction, ash fraction, cancellous cross-sectional area and percent cancellous cross-sectional area), cortical bone (thickness, ash fraction, porosity, cortical cross-sectional area and percent cortical cross-sectional area) and anteroposterior thickness. These parameters were compared with the associated DXA measurements by means of simple and multiple regressions. Cancellous volume fraction was the best predictor of variability of DXA measurements for both the neck and trochanter, with an R ² of 0.87 and 0.76, respectively (p<0.0001). There was only a minor influence of cortical factors such as thickness (neck and trochanter R ²= 0.51 and 0.42, respectively, p<0.001) and trochanteric cross-sectional area (R ²= 0.21, p<0.05). Although the accuracy for determining specific components of the proximal femur was low, the DXA BMD measurement was a strong predictor of cancellous bone factors, but not cortical bone factors that have been shown to change significantly with age. Received: 2 February 2000 / Accepted: 7 September 2000