B. Fan

Comparison of six calcaneal quantitative ultrasound devices : Precision and hip fracture discrimination

Abstract: Quantitative ultrasound (QUS) is now accepted as a useful tool in the management of osteoporosis. There are a variety of QUS devices clinically available with a number of differences among them, including their coupling methods, parameter calculation algorithms and sites of measurement. This study evaluated the abilities of six calcaneal QUS devices to discriminate between normal and hip-fractured subjects compared with the established method of dual-energy X-ray absorptiometry (DXA). The short-term and mid-term precisions of these devices were also determined. Thirty-five women (mean age 74.5 ± 7.9 years) who had sustained a hip fracture within the past 3 years, and 35 age-matched controls (75.8 ± 5.6 years) were recruited. Ultrasound measurements were acquired using six ultrasound devices: three gel-coupled and three water-coupled devices. Bone mineral density was measured at the hip using DXA. Discrimination of fracture patients versus controls was assessed using logistic regression analysis (expressed as age- and BMI-adjusted odds ratios per standard deviation decrease with 95% confidence interval) and receiver operating characteristics (ROC) curve analysis. Measurement precision was standardized to the biological range (sCV). The sCV ranged from 3.14% to 5.5% for speed of sound (SOS) and from 2.45% to 6.01% for broadband ultrasound attenuation (BUA). The standardized medium-term precision ranged from 4.33% to 8.43% for SOS and from 2.77% to 6.91% for BUA. The pairwise Pearson correlation coefficients between different devices was highly significant (SOS, r= 0.79–0.93; BUA, r= 0.71–0.92). QUS variables correlated weakly, though significantly, with femoral BMD (SOS, r= 0.30–0.55; BUA, r= 0.35–0.61). The absolute BUA and SOS values varied among devices. The gel-coupled devices generally had a higher SOS than water-coupled devices. Bone mineral density (BMD) and BUA were weakly correlated with weight (r= 0.48–0.57 for BMD and r= 0.18–0.54 for BUA), whereas SOS was independent of weight. All the QUS devices gave similar, statistically significant hip fracture discrimination for both SOS and BUA measures. The odds ratios for SOS (2.1–2.8) and BUA (2.4–3.4) were comparable to those for femoral BMD (2.6–3.5), as were the area under the curve (SOS, 0.65–0.71; BUA, 0.62–0.71; BMD, 0.65–0.74) from ROC analysis. Within the limitation of the sample size all devices show similar diagnostic sensitivity.

Quantitative Ultrasound of the Tibia Depends on Both Cortical Density and Thickness

Abstract: This study investigated whether tibial speed of sound (SOS; SoundScan 2000, Myriad Ultrasound Systems, Israel) reflects not only bone mineral density (BMD) but also tibial cortical thickness, as assessed by dual-energy X-ray absorptiometry (DXA) and Quantitative CT (QCT) at a site-matched location. The secondary focus of the study was how tibial SOS compares with BMD at the spine and the hip, the most widely used locations for densitometry. Twenty-two young normal (N) and 23 postmenopausal women with spinal fractures (Fx) (mean (SD) age 35 (8) and 70 (5) years) underwent quantitative ultrasound (QUS) SOS measurement at the left tibial midshaft. From site-matched QCT scans (three 3-mm slices spaced along the QUS measurement region), BMD and cortical thickness were computed (QCT-cBMD, QCT-cTh). The cortex in the CT images was then subdivided into three concentric and equally spaced bands, and QCT-cBMD was computed separately for each band. DXA was performed at the mid-tibia (TIB BMD), at the spine (SPINE BMD) and the hip (total hip, HIP BMD). Correlation coefficients between parameters were determined with least-square linear fits. Intergroup differences were assessed by analysis of covariance, whose r2 value reflects the percentage variation in the data explained by group assignment. SOS correlated significantly with site-matched parameters (QCT-cBMD, QCT-cTh and TIB BMD, all r= 0.6, p < 0.001), SPINE BMD and HIP BMD (both r= 0.5, p < 0.001). Multiple regression with both QCT-cBMD and QCT-cTh against SOS yielded r= 0.7 with both parameters contributing significantly. For the cortex band subdivision, SOS correlated better with QCT-cBMD in the outermost band of the cortex (r= 0.67) than with the more central bands (r= 0.59 and r= 0.53). Group assignment could best explain SPINE BMD (r2= 0.62) and HIP BMD (r2= 0.51). SOS was comparable to TIB BMD (r2= 0.3 vs. r2= 0.35).: Our findings suggest that the tibial SOS measurement depends on both the thickness and density of the tibia, but is more strongly influenced by the density of the cortex near the surface than by its interior parts. The power of tibial ultrasound to discriminate between normal and fracture patients was less than that of spinal and femoral DXA BMD and comparable to site-matched DXA BMD.

High resolution magnetic resonance imaging of the calcaneus: age-related changes in trabecular structure and comparison with dual X-ray absorptiometry measurements

Abstract. A high-resolution magnetic resonance imaging (MRI) protocol, together with specialized image processing techniques, was applied to the quantitative measurement of age-related changes in calcaneal trabecular structure. The reproducibility of the technique was assessed and the annual rates of change for several trabecular structure parameters were measured. The MR-derived trabecular parameters were compared with calcaneal bone mineral density (BMD), measured by dual X-ray absorptiometry (DXA) in the same subjects. Sagittal MR images were acquired at 1.5 T in 23 healthy women (mean age: 49.3 ± 16.6 [SD]), using a three-dimensional gradient echo sequence. Image analysis procedures included internal gray-scale calibration, bone and marrow segmentation, and run-length methods. Three trabecular structure parameters, apparent bone volume (ABV/TV), intercept thickness (I.Th), and intercept separation (I.Sp) were calculated from the MR images. The short- and long-term precision errors (mean %CV) of these measured parameters were in the ranges 1–2% and 3–6%, respectively. Linear regression of the trabecular structure parameters vs. age showed significant correlation: ABV/TV (r2= 33.7%, P < 0.0037), I.Th (r2= 26.6%, P < 0.0118), I.Sp (r2= 28.9%, P < 0.0081). These trends with age were also expressed as annual rates of change: ABV/TV (− 0.52%/year), I.Th (−0.33%/year), and I.Sp (0.59%/year). Linear regression analysis also showed significant correlation between the MR-derived trabecular structure parameters and calcaneal BMD values. Although a larger group of subjects is needed to better define the age-related changes in trabecular structure parameters and their relation to BMD, these preliminary results demonstrate that high-resolution MRI may potentially be useful for the quantitative assessment of trabecular structure.

Assessment of Bone Mineral at Appendicular Sites In Females With Fractures of the Proximal Femur

The prediction of hip fractures by measurements at remote sites or the improvement of predictive power by measurements at multiple sites could potentially increase the success of osteoporosis screening programs. In a cross-sectional study on 137 postmenopausal women, we tested the hypothesis that bone assessment at the hip, the forearm, and the tibia are independently associated with osteoporotic fractures of the hip. Bone mineral densities, geometric features, and ultrasound properties were determined with hip dual X-ray absorptiometry, forearm peripheral quantitative computed tomography (QCT), and tibia speed of sound measurement. While the odds ratios for fracture discrimination per standard deviation decrease ranged between 3 and 4 for measurements at the hip, they were only 1.8 at the forearm and 1.4 at the tibia. Measurements at the tibia or the forearm were neither independently associated with osteoporotic hip fractures (p > 0.05) nor could any combination of measurements significantly increase the power for the identification of fractures as measured with receiver operating curves. Women who sustained trochanteric fractures were characterized by a generalized loss of bone mineral. Cervical fractures were associated with a decrease of bone mineral density at the hip, but no significant alterations in bone mass or geometric properties were observed at the tibia or at the forearm. Fracture risk prediction at the hip is therefore preferably performed by measurements at the hip itself. Peripheral QCT at the distal radius and tibial ultrasound seem capable of depicting women with an increased risk for trochanteric but not for cervical fractures. The risk assessment appears not to be improved by including information of cortical or geometric properties of the forearm.

Assessment of a new quantitative ultrasound calcaneus measurement: Precision and discrimination of hip fractures in elderly women compared with dual X-ray absorptiometry

Abstract: The incidence of osteoporotic hip fracture increases in postmenopausal women with low hip bone mineral density (BMD). Dual X-ray absorptiometry (DXA) is the most commonly used technique for the assessment of bone status and provides good measurement precision. However, DXA affords little information about bone architecture. Quantitative ultrasound (QUS) systems have been developed to evaluate bone status for assessment of fracture risk. Our study was designed to assess a new QUS system from Hologic, the Sahara; to compare it with a previous model, the Walker-Sonix UBA 575+; and to investigate whether it is able to discriminate between women with and without fracture. Using both ultrasound devices, the measurements were performed at the heels of 33 postmenopausal women who had recently sustained hip fracture. A control group of 35 age-matched postmenopausal women was recruited for comparison. The total, neck and trochanter femoral BMD values were assessed using DXA for both groups. QUS and DXA measurements were significantly lower in fractured patients (p<0.005) than in the control group. The short-term, mid-term and standardized short-term precisions were used to evaluate the reproducibility of the two QUS systems. The Sahara showed a better standardized coefficient of variation for broadband ultrasound attenuation (BUA) than did the UBA 575+ (p<0.001). The correlation of BUA and speed of sound (SOS) between the two QUS devices was highly significant, with an r value of 0.92 for BUA and 0.91 for SOS. However, the correlation between DXA and ultrasound parameters ranged from 0.28 to 0.44. We found that ultrasound measurements at the heel were significant discriminators of hip fractures with odds ratios (OR) ranging from 2.7 to 3.2. Even after adjusting the logistic regressions for total, neck or trochanter femoral BMD, QUS variables were still significant independent discriminators of hip fracture. The areas under the ROC curves of each ultrasound parameter ranged from 0.75 to 0.78, and compared very well with femoral neck BMD (p>0.05). In conclusion, our study indicated that the calcaneal QUS variables, as measured by the Sahara system can discriminate hip fracture patients equally as well as hip DXA.

Palangeal Quantitative Ultrasound, Phalangeal Morphometric Variables, and Vertebral Fracture Discrimination

The aim of this study was to evaluate the association among phalangeal morphometric parameters, amplitude-dependent speed of sound (AD-SOS), ultrasound bone profile index (UBPI), and spinal bone mineral density (BMD) and fracture status. One hundred women (controls, mean age 53 ± 12 years) and 40 osteoporotic women (mean age 59 ± 7 years) with atraumatic fractures, diagnosed by spinal radiographs, were investigated. Quantitative ultrasound (QUS) assessment was performed using the DBM Sonic 1200. Morphological properties of the phalanges were measured from a digitized X-ray image of the hand acquired using industrial film. Spinal BMD was assessed by dual X-ray absorptiometry (DXA) and quantitative computed tomography (QCT). An increase in medullary canal width and a decrease in cortical thickness with aging were observed from the morphometric analysis of the hand radiographs. This phenomenon can be attributed mainly to endosteal resorption. QUS measurements at the phalanges were not significantly related to finger thickness (r <0.20, n.s.). They were significantly correlated to medullary canal ratio (r = -0.57, P <0.0001, for AD-SOS and r = -0.64, P <0.0001, for UBPI) and to cortical thickness (r = +0.52, P <0.0001 for AD-SOS and r = +0.59, P <0.0001 for UBPI). In the discrimination analysis between nonfractured and atraumatic vertebral fracture subjects we found that cortical thickness at the level of the phalanges were similar to lumbar spine BMD. The age and BMI-adjusted odds ratio ranged from 2.0 to 3.1 for QUS, 4.28 for BMD by QCT, 4.1 for BMD by DXA, and 4.1 for cortical thickness. We conclude from these data that phalangeal QUS is related to cortical thickness, which in turn is influenced by endosteal bone resorption occurring in association with spinal osteoporosis.

Vertebral morphometry: a comparison of long-term precision of morphometric X-ray absorptiometry and morphometric radiography in normal and osteoporotic subjects.

Abstract: Vertebral morphometry, the quantification of vertebral body shape, has proved a useful tool in the identification and evaluation of osteoporotic vertebral deformities in both epidemiologic surveys and clinical trials. Although conventionally it has been performed on lateral radiographs of the thoracolumbar spine (morphometric radiography, MRX), it may now be accomplished on morphometric X-ray absorptiometry (MXA) scans, acquired on dual-energy X-ray absorptiometry (DXA) machines. In this study the long-term precision of vertebral height measurement using MXA and MRX was directly compared. Initially 24 postmenopausal women were recruited (mean age 67 ± 5.8 years): 12 normal subjects (group 1) and 12 with osteoporosis and known vertebral deformities (group 2). Each subject attended for a baseline visit at which they had a MXA examination and lateral thoracic and lumbar radiographs. Twenty-one subjects then returned 1.7 ± 0.4 years later (10 subjects from group 1 and 11 from group 2) for a follow-up visit to repeat both the MXA scans and conventional radiographs. The baseline MXA scans and conventional radiographs were each analyzed quantitatively by two observers in a masked fashion, using a standard six-point method. The follow-up images were then analyzed by the same observers. The MRX observers were masked to the baseline analyses, while the MXA observers utilized the manufacturer’s ‘compare’ facility. On all scans and radiographs anterior (Ha), mid (Hm) and posterior (Hp) vertebral heights were measured and wedge (Ha/Hp) and mid-wedge (Hm/Hp) ratios calculated for each vertebral body, ideally from T4 to L4. MRX analyzed 129 of the 130 available vertebrae in group 1 at both visits and 141 of the 143 available in group 2, while MXA analyzed 124 vertebrae in group 1 at both visits and 127 in group 2. Intra- and inter-observer precision errors, particularly in terms of coefficient of variation (CV%), were larger for MXA than for MRX in both normal subjects and those with vertebral deformities. For example, intra-observer precision errors for vertebral height measurement were 0.62 mm (2.9%) for MXA compared with 0.63 mm (2.2%) for MRX in group 1 (normal) subjects and 0.82 mm (4.2%) for MXA compared with 0.85 mm (3.3%) for MRX for group 2 (osteoporosis and vertebral deformities) subjects. Both MXA and MRX inter-observer precision was clearly poorer than the intra-observer precision, a problem associated with any morphometric technique. This was particularly noticeable for MXA; for example, precision of vertebral height measurement in group 1 subjects was 0.62 mm (2.9%) for intra-observer compared with 0.99 mm (4.6%) for inter-observer analyses. MXA and MRX intra- and inter-observer precision was significantly poorer for subjects with vertebral deformities compared with those without, with the CV% for subjects with vertebral deformity approximately 50% greater than that of normal subjects. For example, MRX intra-observer precision for the mid-wedge ratio was 2.6% for group 1 subjects compared with 3.8% for group 2 subjects. The precision of vertebral height measurement on deformed vertebrae of group 2 subjects was poorer than that for normal vertebrae in the same subjects using both MXA and MRX, as a result of increased variability in point placement. For example, MXA intra-observer precision (RMS SD) for the wedge ratio precision was 0.037 (3.9%) for normal vertebrae compared with 0.060 (6.6%) for deformed vertebrae. We conclude that MXA precision was generally poorer than MRX, although both techniques were adversely affected by the presence of vertebral deformities and the use of more than one observer. Although precision errors for both techniques were substantially smaller than the 20–25% reduction in vertebral height frequently proposed to identify incident deformities, the poorer precision of MXA may lead to an increased risk of erroneous classification of vertebrae as normal or deformed.

Morphometric X-ray absorptiometry and morphometric radiography of the spine: a comparison of analysis precision in normal and osteoporotic subjects.

Abstract: Morphometric techniques, which use conventional lateral spine radiographs to quantify vertebral body shape (morphometric radiography, MRX), have proved a useful tool in the identification and evaluation of osteoporotic vertebral deformities. Recently a new method of acquiring the images required for vertebral morphometry using dual-energy X-ray absorptiometry scanners (morphometric X-ray absorptiometry, MXA) has been developed. In this study we compare repeat analysis precision of vertebral height measurement using MXA and MRX. Twenty-four postmenopausal women were recruited (mean age 67 + 5.8 years): 12 normal subjects and 12 with osteoporosis and vertebral deformities. Each subject had a MXA scan and lateral thoracic and lumbar radiographs at a single appointment, which were each analyzed quantitatively in a masked fashion, using a standard 6-point method, twice by one observer and once by a second observer. Anterior (Ha), mid (Hm) and posterior (Hp) vertebral heights were measured and wedge (Ha/Hp) and mid-wedge (Hm/Hp) ratios calculated for each vertebral body. Intra- and interobserver precision were consistently poorer in MXA compared with MRX in both normal subjects and those with vertebral deformities, with MXA CV% generally at least 50% higher than corresponding values for MRX. For both MXA and MRX interobserver precision was clearly poorer than intraobserver precision, a problem associated with any morphometric technique. MXA intra- and interobserver precision were significantly poorer for subjects with vertebral deformities compared with those without, with a CV% for deformity subjects up to twice that of normal subjects. Conversely, MRX showed little or no obvious worsening of intra- or interobserver precision for deformity subjects. Comparison of MXA precision in the normal and deformed vertebrae of the deformity subjects demonstrated that the poorer precision in these subjects compared with normal subjects was the result of increased variability in point placement on the deformed vertebrae themselves. However, the precision for normal vertebrae in these subjects was also somewhat poorer than the precision in normal subjects. We conclude that MXA precision is generally poorer than that of MRX and that the presence of vertebral deformities has a more pronounced effect on MXA precision than on MRX precision.

Factors affecting broadband ultrasound attenuation results of the calcaneus using a gel-coupled quantitative ultrasound scanning system.

Abstract: This study aimed to assess the factors that may influence the distribution and description of broadband ultrasound attenuation (BUA) and to identify specific criteria for diagnostic consideration when collecting BUA reference data. Two hundred Caucasian women (aged 20–79 years) without a history of atraumatic fractures or medicines known to affect bone metabolism were selected for this study. Medical and menstrual history, medication usage, family history of osteoporosis (FHO), physical activity, activities of daily living (ADL), dietary calcium intake, as well as smoking and alcohol consumption were obtained. Broadband ultrasound attenuation (BUA, dB/MHz) was determined in the right foot using a new gel-coupled ultrasound system. BUA was significantly associated with age (p<0.001), body weight (p<0.001), level of physical activity (p = 0.024) and dietary calcium intake (p= 0.023). Smoking, alcohol and coffee consumption and ADL were not associated with BUA (p>0.05). There were no differences in BUA (p>0.05) between those women who reported taking medications or had diseases (known to not affect bone metabolism), were using contraceptives, taking vitamin/mineral supplements and/or had traumatic fractures and their counterparts who did not report these characteristics. Premenopausal women with a FHO had significantly lower BUA values compared with those without a FHO (p= 0.013). When those participants with a FHO were removed from the sample, the peak BUA value was 1.1–4.4% higher and the variability (SD) was reduced by about 3.3–9.3% depending on which age range was used to define the peak BUA value. Consequently, an additional 4.5% of the population were classified as having a T-score <−2. Our results suggest that the impact on BUA of risk factors such as a FHO, body weight, physical activity and dietary calcium intake is similar to that on bone mineral density obtained by dual-energy X-ray absorptiometry (DXA), and thus provides further information on the comparability of quantitative ultrasound and DXA for assessment of risk of fracture. The criteria for calculating the T-score need further study to determine whether young adults with FHO should be included and what cutoff age range should be used in collecting peak values of quantitative ultrasound parameters.

Prediction of Bone Strength of Distal Forearm Using Radius Bone Mineral Density and Phalangeal Speed of Sound

This investigation compares quantitative ultrasound (QUS) measurement of the phalanges with peripheral quantitative computed tomography (pQCT) and dual X-ray absorptiometry (DXA) measurement of the forearm, to estimate the strength of the distal radius in 13 cadaveric forearms. The cadavers were scanned at the distal radius by pQCT and DXA for bone mineral density (BMD) and at the approximate phalanges by QUS for speed of sound (SOS). The distal radii were subjected to a simulated Colles fracture produced with a materials testing machine. The load at which the distal radius was fractured was considered as a representation of bone strength. The bone strength correlated significantly with SOS at different phalanges (r = 0.63-0.72), BMD at different regions of interest by DXA (r = 0.67-0.75), and cortical BMD at different sites by pQCT (r = 0.61-0.67). Standard stepwise regression analysis showed that adding phalangeal SOS into forearm densitometric variables significantly enhanced the statistical power for prediction of the strength of the distal radius. Our results suggest that, for assessment of site-specific distal forearm strength, QUS measurement of the phalanges is comparable to forearm densitometry. Phalangeal QUS may add clinical value if distal forearm strength has a high priority.