Precision and accuracy of measuring changes in bone mineral density by dual-energy X-ray absorptiometry.

UNLABELLED: Long-term precision of two Hologic DXA scanners was derived from repeated clinical measurements. With typical subjects, the long-term coefficients of variation were about twice the short-term. The accuracy of the measurement of changes was compromised by anomalies, but this did not seriously affect clinical conclusions. INTRODUCTION: Long-term precision and accuracy of BMD measurements need review. METHODS: Long-term precision was examined by selecting, from Hologic databases, subjects who had had four scans over a period of 2 to 5 years and was calculated from the SEE of a regression of BMD against time. Accuracy was assessed from relationships between changes (delta) in BA, BMD and BMC. RESULTS: For one group of subjects, the long-term precision was 2.4% for lumbar spine, 2.3% for total hip and 2.7% for femoral neck when expressed as CVs. These values were nearly twice the short-term CVs of 1.3% for spine, 1.2% for total hip and 1.4% for femoral neck. For another group, a negative exponential regression gave a better fit, leading to CVs of 1.3% for the spine, 1.4% for total hip and 2.1% for femoral neck. Significant correlations between deltaBA and deltaBMC were found. These led to an underestimate of deltaBMD in spine and hip by 25%. CONCLUSIONS: The poorer long-term precision for typical patients should be borne in mind in monitoring progress. The underestimate of changes could account for only a part of the underestimation by BMD measurements of the anti-fracture effects of anti-resorptive drugs.

Dual-energy X-ray absorptiometry measurements of fat and lean masses in subjects with eating disorders.

OBJECTIVE: The main objective was to use a dual-energy X-ray absorptiometer (DXA) to examine the total-body and regional fat and lean composition of soft tissue in subjects with and without eating disorders initially and after weight change. It was necessary also to study the effects of differences of calibration of different models of DXA scanner. DESIGN: A total of 175 women with eating disorders, including anorexia nervosa (AN) and bulimia nervosa, and 43 age-matched controls were measured for soft-tissue composition with a pencil-beam Hologic QDR 1000W scanner and results converted to be equivalent to those from a fan-beam Hologic QDR 4500A, using previously determined crosscalibration factors. Some measurements were repeated at 6 and 12 months. RESULTS: The baseline body composition of the patients covered a continuous range of fat proportions. Implausibly low fat proportions in some of the AN subjects were corrected by conversion to 4500 equivalents. The relationship between total lean mass and fat mass could be fitted equally well by a linear or linear/log regression. The relationship between leg and trunk fat was best fitted by a polynomial regression. There were weight changes in either direction in some of the subjects. The fat proportion in the total changed mass was a mean of 55%, higher in the legs and lower in the trunk, but not different between weight gainers and losers or clinical groups. The proportion was dependent on the initial fat proportion. CONCLUSIONS: Relatively small differences in fat/lean calibration of DXA scanners may lead to anomalous results in very anorexic subjects and corrections are necessary in comparing results from different instruments. Concerns expressed about preferential trunk fat accumulation during weight recovery are not well founded. Previous claims of a relationship between fat proportion in regained weight and the amount of the weight gain are not justified.

Bone mineral and soft tissue measurements by dual-energy X-ray absorptiometry during growth.

There have been several previous compilations of reference ranges of total body bone mineral measured by dual-energy X-ray absorptiometry (DXA) in children and young adults during growth, but little attempt to compare the results or to consider differences arising from the use of instruments from different manufacturers. We measured bone mineral and soft tissue in 216 girls, aged 11-17 years, using a Hologic scanner. Our results were compared with those from four other studies, all performed on white subjects, but in different countries, and including measurements performed with Hologic, Lunar, and Norland scanners. The general pattern of bone growth with age was very similar in all the studies. Quantitative differences could largely be accounted for by known differences of calibration of DXA scanners from the different manufacturers. When bone mass was plotted against lean or total mass instead of age there were also close similarities. An apparent difference between boys and girls in one study was shown to be due to differences in soft tissue composition, rather than different patterns of bone growth. Conclusions from this apparent difference concerning the effect of estrogen at puberty were shown to be unwarranted.

Comparisons between a pencil beam and two fan beam dual energy X-ray absorptiometers used for measuring total body bone and soft tissue.

A pencil beam Hologic QDR 1000W scanner (1000), a fan beam QDR 4500A scanner (4500) and a fan beam Lunar Expert scanner (Expert) were compared for bone mineral and body composition measurement accuracy. Phantoms were scanned with each instrument to assess magnification effects and to compare calibrations for bone mineral and fat proportion. 41 volunteers were scanned with both the 1000 and the 4500, and 21 patients with both the 4500 and the Expert. The height of a bone within the body affected the measured bone mineral content (BMC) and, to a lesser extent, the bone mineral density (BMD). There were differences in calibration against recognized standards for fat proportion between the three instruments. The 1000 underestimated low fat proportions and the 4500 underestimated high fat proportions. Fat results for the Expert were closer to nominal values. Comparisons on volunteers showed that measured mean total body BMD was 4% higher and BMC was 7% higher with the 1000 compared with the 4500; some regional differences were greater. Mean values of per cent fat were equal, but the total and regional regression coefficients were well above unity. Mean BMD was 3% higher and mean BMC was 10% higher with the Expert compared with the 4500, but most regression coefficients for these comparisons were less than unity. Mean values of per cent fat were equal, but regression coefficients were above unity. Errors due to magnification are acceptable. Differences between the instruments are appreciable, but can be accommodated by cross-calibration.

Comparisons between Hologic QDR 1000W, QDR 4500A, and Lunar Expert dual-energy X-ray absorptiometry scanners used for measuring total body bone and soft tissue.

Measurements of total-body bone and soft tissue were compared between two fan-beam dual-energy X-ray absorptiometry (DXA) scanners, a Hologic QDR 4500A, a Lunar Expert, and a pencil-beam Hologic QDR 1000W. Phantom studies showed that mass measurements were not compromised by magnification effects, but that the height of a bone within the body affected the measured bone mineral content (BMC) and, to a lesser extent, the bone mineral density (BMD). There were differences in calibration for fat proportion between the three instruments. Comparisons on volunteers demonstrated very high correlations of bone and soft tissue measurements, but regression coefficients differed from unity, and intercepts were significant. With all three scanners, wrapping lard around the limbs of a volunteer, to simulate weight change, changed the apparent BMC and BMD.

Measurement of abdominal fat by magnetic resonance imaging, dual-energy X-ray absorptiometry and anthropometry in non-obese men and women.

OBJECTIVE: To investigate whether the dual-energy X-ray absorptiometry (DEXA) was a better predictor of abdominal fat, measured by magnetic resonance imaging (MRI) at the level of L2-L3, than anthropometric measurements in non-obese men and non-obese women. DESIGN: Observational, cross sectional study. SUBJECTS: 34 healthy subjects (17 men and 17 women) aged 20-53 y with a body mass index (BMI) < 30 kg/m2. MEASUREMENTS: Fat distribution parameters including waist circumference and waist-to-hip ratio (WHR); intra abdominal fat (IAF) by MRI; and central abdominal fat (CAF) by DEXA. RESULTS: Measurement of IAF by MRI, was highly correlated to the CAF measured by DEXA. In men, both waist circumference and WHR had similar correlation to IAF as DEXA. In women, waist circumference was less well correlated with IAF than DEXA, and the WHR had a weaker non significant correlation with IAF. CONCLUSIONS: In non-obese men; DEXA, waist circumference and WHR can predict IAF equally well, while in non-obese women, DEXA is superior to waist circumference and much better than WHR.

Anomalies in dual energy X-ray absorptiometry measurements of total-body bone mineral during weight change using Lunar, Hologic and Norland instruments.

A previous study showed that measurements of total-body bone mineral changes made with a Hologic QDR 1000W were unreliable when the subjects underwent weight change. The study has been extended to dual energy X-ray absorptiometry (DXA) apparatus from other manufacturers. Re-analysis of published results during weight loss using a Lunar DPX showed that they varied with the software used. Using the Extended mode, there was a 1% loss of bone mineral areal density (BMD), but no significant change in bone mineral content (BMC) or bone area (BA) following a weight loss of 16 kg, whereas the use of the Standard mode led to a larger fall of BMC and BMD. Similar findings arose from the consideration of two studies using Norland XR 26 HS absorptiometers. On the other hand, separation of two groups with similar weight changes from the population studied with a Hologic QDR 1000W confirmed that BMC changed directly with weight, but there was an inverse relationship for BMD, owing to an inappropriate change of BA. The use of Hologic Enhanced and Standard software modes led to significant differences in initial readings and measured changes. With each instrument there was a strong correlation between changes in BA and changes in BMC. When 6 kg of lard was wrapped around the limbs of volunteers or a semi-anthropomorphic phantom to simulate weight change, there were spurious increases of measured BMC and BA by about 5% with each instrument. There were no changes of BMD with Lunar, variable results with Norland, but decreases with Hologic. The results observed in vivo could be explained by the effects of fat changes, without there being any real change of bone mineral. Changes of BMD in the skeleton of the phantom were underestimated with all three brands. The anomaly observed with the Hologic QDR 1000W is less apparent with a Lunar DPX or a Norland XR 26, but there are sufficient uncertainties for all total-body measurements during weight change to be treated with suspicion.

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 1000 W, 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.

Anomalies in the measurement of changes in total-body bone mineral by dual-energy X-ray absorptiometry during weight change.

For an eating disorder study over a period of 1 year, we measured total-body bone mineral using a Hologic QDR 1000 W in a total of 157 subjects and observed anomalies that questioned the accuracy of such measurements. Using the recommended Enhanced software, a change in total bone mineral content (delta BMC) correlated positively with a change in weight (delta W; r = 0.66), but a loss of weight was associated with an increase in bone mineral areal density (BMD; r = 0.58), arising from a reduction in bone area (AREA). Both regressions were highly significant. The dominant factor in this relationship was a strong correlation between delta AREA and delta BMC, for all parts of the skeleton, r > 0.9, with a slope close to 1. This is implausible because bone area would not be expected to change. When Standard software was used, the slope of the delta BMC/delta W correlation was steeper, but the delta BMD/delta W regression became positive. An artefact of dual-energy X-ray absorptiometry processing was suspected, and phantom measurements were made. The phantom consisted of tissue-equivalent hardboard cut and stacked to form cylinders corresponding to the head, trunk, arms, and legs of a standard man. The skeleton was constructed from layers of aluminium sheet as an approximation of the average shape, BMD, BMC, and AREA in each region. When aluminium thickness was varied, BMD thresholds were found, approximately 0.4 g/cm2 for the legs and 0.2 g/cm2 for the arms. Above these, bone area rose fairly rapidly toward a plateau. At higher skeletal densities, the relationships between measured and true BMDs were close to linear, but slopes were less than unity, so that changes would be underestimated by 10-30%. Increases of thickness of the soft tissue of the phantom lowered AREA slightly. Uniform fat proportion increases led to decreases in BMC and AREA, but lard wrapped in an annulus around the limbs led to spurious increases in BMC and AREA of a similar magnitude to those observed in vivo, while BMD fell slightly, although there had been no true change of bone variables. Similar results were obtained with lard around the limbs of a volunteer. Reanalysis of phantom scans using Standard software confirmed the software differences noted in vivo. The phantom measurements offer an explanation of the anomaly in vivo and demonstrate that, under different circumstances, change in both BMC and BMD can be wrongly recorded. We believe that no valid conclusions can be drawn from measurements by the Holgic QDR 1000 W of bone changes during weight change.

Comparisons between fat measurements by dual-energy X-ray absorptiometry, underwater weighing and magnetic resonance imaging in healthy women.

OBJECTIVE: To compare the results of measurements of total and regional fat by dual-energy X-ray absorptiometry (DXA), underwater weighing (UWW) and magnetic resonance imaging (MRI) in women. DESIGN: 13 volunteer pre-menopausal women measured with a Norland XR26 HS DXA instrument, hydrodensitometry equipment and a 0.08 Tesla MRI scanner. SETTING: Aberdeen Royal Infirmary. RESULTS: There were high correlations between measurements of total-body fat by the different techniques, but poor agreement. The mean values of fat as a percentage of the total body mass were UWW = 28.6%, DXA = 40.0%, MRI = 23.0%, although the MRI excluded the head, forearms and feet, estimated from the DXA measurements to contain 8% of the body fat. Although the correlations were apparently linear in the ranges examined, those including the Norland DXA had high intercepts. Bland and Altman plots showed no dependence of the differences on the degree of fatness. Evidence was obtained from in vivo comparisons and phantom measurements that the fat calibration of the Norland DXA had changed during a three year period, suggesting that fat calibration errors contributed to the MRI/DXA differences. Previous comparisons between the Norland DXA and other brands indicate that Hologic and Lunar instruments would show a closer agreement with MRI and UWW. Profiles of fat distribution along the body showed variations in the DXA/MRI ratio, particularly in the chest, with the DXA pattern thought to be the less accurate. The DXA measurements of bone mineral, fat and lean tissue were used to demonstrate the variable proportion of bone in fat-free tissue, leading to errors in UWW. CONCLUSIONS: Each method has its assumptions, which are often not sufficiently appreciated. Each method may be useful for testing and improving the assumptions in the other methods. No method can yet be regarded as a satisfactory reference technique.

Changes in blood volume distribution between legs and trunk during halothane anaesthesia.

To assess the influence of halothane anaesthesia on the distribution of blood volume in supine humans, we used albumin labelled with 99mTc to measure blood volume distribution along the craniocaudal axis. We studied 6 volunteers in the supine position before, during and after anaesthesia with 1% halothane and 66% nitrous oxide. Using collimated detectors above and below the subject, counts were obtained from the legs, pelvis, abdomen, rib cage and head, with the arms excluded. During anaesthesia, the proportion of counts detected in the legs increased, but failed to achieve significance (P = 0.059). On recovery from anaesthesia, leg counts decreased significantly. Counts in the abdomen and rib cage decreased significantly during anaesthesia and the abdomen counts increased again on recovery (P = 0.036 for all changes). These results confirm other studies of the vascular effects of halothane, and do not support the hypothesis that blood volume redistributes from the legs to within the chest wall during anaesthesia.

Comparisons between three dual-energy X-ray absorptiometers used for measuring spine and femur.

Lunar, Hologic and Norland dual-energy X-ray absorptiometry scanners have been compared for measurements of spine and femur bone density. Precision was not greatly different in realistic phantoms and volunteer subjects. Most clinical therapeutic trials are concerned with measuring changes of bone mineral, and interchangeability in this context was examined using phantoms of spine and femur in which changes of bone mineral density (BMD) were simulated. With each instrument the measured changes were closely linear. For the spine the biggest difference of slope between instruments was 15%. For the femur, in all areas of interest, the differences of slope were less than 10%. It is concluded that the three instruments can be satisfactorily used in multicentre clinical trials to investigate changes in bone mineral. 12 volunteers were measured with each scanner. There were significant mean differences between each pair of instruments, suggesting different calibration criteria. More importantly, those mean differences had appreciable standard deviations (SDs), in proportional terms from 3% to 10%. When the measurements were related to reference ranges and expressed in terms of age-matched normal values the mean biases disappeared, but the SDs did not improve. Results from different manufacturers' apparatus are not interchangeable for studying individual patients. Measurements from the phantoms were used to cross-calibrate the scanners. Those from the variable spine phantom predicted the in vivo ratio within 4%, but this was no better than measurements of the unmodified phantom alone. Results using the European Spine Phantom were less satisfactory. No phantom provided an adequate cross-calibration for femur measurements.

Precision and accuracy of measurements of whole-body bone mineral: comparisons between Hologic, Lunar and Norland dual-energy X-ray absorptiometers.

Measurements of whole-body bone mineral made by Hologic, Lunar and Norland dual-energy X-ray absorptiometers have been compared. It was found that in each case the results were changed by new software protocols introduced by the manufacturers during the course of the study. With a moderately anthropomorphic model, the later software corrected some anomalies of regional bone mineral content (BMC) observed earlier. There was some slight dependence of total BMC on thickness and fat proportion and up to 15% difference between instruments. Measurements on volunteers showed good precision, but there were differences between instruments made by different manufacturers. There were high correlations, but the slopes of regression lines suggested differences of calibration of up to 8%; the standard errors of the estimates were 110 to 190 g. with maximum deviations from regression of 17%. There were regional disparities in BMC, particularly in the trunk, which arise (in part at least) from the imposition of a higher bone threshold by Hologic. From the pattern of results it was concluded that different assumptions were made by the manufacturers, particularly concerning the fat distribution model, which preclude the interchangeability of results from different instruments.