Comparison of Six Calcaneal Quantitative Ultrasound Devices: Precision and Hip Fracture Discrimination

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. Received: 2 February 2000 / Accepted: 1 May 2000     

In Vivo MRI Measurements of Bone Quality in the Calcaneus: A Comparison with DXA and Ultrasound

Magnetic resonance imaging (MRI) has shown promise in the assessment of bone architecture. The precision and feasibility of MRI measurements in osteoporosis in vivo have been assessed in this study. T2′ was calculated from measurements of T2 and T2* in the calcaneus of 32 postmenopausal women using a gradient-echo sequence PRIME (Partially Refocused Interleaved Multiple Echo). This sequence allows the measurement of T2 and T2* in one acquisition. In vivo measurements of bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA) were made in the calcaneus, spine and femoral neck. The ultrasound parameters broadband ultrasound attenuation (BUA) and speed of sound (SOS) were also measured in the calcaneus. These three techniques have not previously been compared in the same study population. The precision of the MRI technique was poor relative to the DXA and ultrasound techniques, with a CV of 6.9%± 4.4% for T2′ and 5.5%± 3.6% for T2*. Approximately 4% of this is due to system error as determined by phantom measurements. The postmenopausal women were classified as having low BMD if they had a lumbar spine (L2–4) BMD of less than 0.96 g/cm² (more than 2 standard deviations below normal peak bone mass). Calcaneal T2′ was significantly correlated with calcaneal BMD (r = –0.79, p <0.0001), BUA (r = –0.59, p = 0.0004) and SOS (r = –0.58, p = 0.0006). T2′ was significantly different in postmenopausal women with normal BMD and those with low BMD (p <0.01). However, the difference was of only borderline significance (p <0.06) after adjustment for age and years since menopause. Received: 8 July 1997 / Accepted: 29 April 1998     

Does Quantitative Ultrasound Imaging Enhance Precision and Discrimination?

The aim of this study was to compare quantitative ultrasound (QUS) measurements obtained using a new calcaneal QUS imaging device with a conventional non-imaging device using fixed transducers. The study group consisted of 340 healthy women with no risk factors associated with osteoporosis (176 premenopausal and 164 postmenopausal) and 83 women with one or more vertebral fractures. All women had QUS measurements performed on the Osteometer DTU-one (imaging) and Walker-Sonix UBA575+ (non-imaging) devices and bone mineral density (BMD) measurements performed at the spine and hip. A subgroup of 81 women had additional dual-energy X-ray absorptiometry (DXA) scans at the calcaneus. Short-term standardized precision (SP = SD/young adult SD) based on duplicate measurements was significantly better on the DTU for broadband ultrasound attenuation (BUA) (SP: DTU 0.15 vs UBA 0.21, p= 0.01) and speed of sound (SOS) (SP: DTU 0.14 vs UBA 0.18, p= 0.01). However, long-term SP of the DTU was comparable to or significantly poorer than the SP of the UBA device. The BUA and SOS measurements obtained on the DTU and UBA were significantly correlated (r= 0.76 and 0.89 for BUA and SOS measurements respectively). The correlations between QUS and BMD measurements were all significant, ranging from 0.53 to 0.72. No significant improvements in the correlation with axial or peripheral BMD were observed using the imaging device. All the QUS measurement parameters showed a significant negative relationship between age and years since menopause in the postmenopausal group. Annual losses were lower for the DTU for BUA (DTU 0.22 dB/MHz per year vs UBA 0.44 dB/MHz per year) but comparable for SOS (DTU 0.29 m/s per year vs UBA 0.22 m/s per year). However, when these figures were standardized to take into account the clinical range, the annual losses were similar on the DTU and UBA. Age-adjusted odds ratios for each SD decline were similar on the DTU for BUA (DTU 3.2 vs UBA 3.3) and SOS (DTU 3.4 vs UBA 5.1). The corresponding odds ratios for BMD at the lumbar spine, femoral neck and total hip were 2.7, 2.9 and 3.3 respectively. Age-adjusted receiver-operating characteristics analysis yielded values for the area under the curve (AUC) ranging from 0.74 to 0.83. The DTU BUA AUC of 0.83 was significantly greater than the AUC obtained for UBA BUA and BMD measurements at the lumbar spine and femoral neck. Ultrasound imaging at the calcaneus was found to improve the standardized precision of BUA and SOS measurements in the short term but not in the long term. Neither the correlation with BMD nor the discriminatory ability of QUS was improved by utilizing QUS images at the calcaneus. The inconsistencies of the imaging system used for this study demonstrate that further development is required before it will be possible to show improvements in long-term precision. Received: 18 June 1999 / Accepted: 29 October 1999     

Contact Quantitative Ultrasound: An Evaluation of Precision, Fracture Discrimination, Age-Related Bone Loss and Applicability of the WHO Criteria

The aim of this study was to assess a dry calcaneal quantitative ultrasound (QUS) device by examining: (i) short- and long-term precision; (ii) the ability of the ultrasound parameters to identify women with vertebral fractures; (iii) age- and menopause-related bone loss; (iv) applicability of the WHO criteria in scan interpretation. The study group consisted of 422 healthy women with no risk factors associated with osteoporosis (227 premenopausal and 195 postmenopausal) and 93 women with one or more vertebral fractures. All women had calcaneal QUS and bone mineral density (BMD) measurements of the lumbar spine and hip performed. Broadband ultrasound attenuation (BUA) and speed of sound (SOS) measurements in the heel were combined and expressed as estimated heel BMD. Short-term precision studies yielded coefficient of variations of 0.3% for SOS, 4% for BUA and 3.3% for estimated heel BMD. Standardized short-term precision values were approximately 0.2 SD. Long-term standardized precision errors ranged from 0.17 to 0.38 SD. All the QUS and BMD measurement parameters showed significant negative relationships with age in the postmenopausal group. Annual losses were 0.35 dB/MHz per year for BUA, 0.56 m/s per year for SOS and 0.002 g/cm² per year for estimated heel BMD. All the QUS and BMD parameters were able to discriminate between healthy postmenopausal women and women with vertebral fracture. Age-adjusted odds ratios for each SD decline in QUS measurements were 3.63, 5.25 and 4.79 for BUA, SOS and estimated heel BMD respectively. Corresponding odds ratios for BMD at the lumbar spine, femoral neck and total hip were 2.39, 2.51 and 2.95 respectively. When the QUS and BMD parameters were expressed as T-scores, estimated heel BMD showed the least age-related decline, while femoral neck BMD displayed the greatest decrease with age. The mean T-score and prevalence of osteoporosis (T<−2.5) for a Caucasian woman aged 60–65 years were −1.35 and 21% respectively for the lumbar spine compared with −0.59 and 2% for estimated heel BMD. In conclusion, this study revealed that contact ultrasound can detect age- and menopause-related influences on bone status and was able to discriminate between healthy individuals and women with vertebral fracture. However, the widely accepted threshold of a T-score of less than −2.5 for the definition of osteoporosis may need modifying for the interpretation of QUS scans. Received: 8 February 1999 / Accepted: 5 May 1999     

Ultrasound Measurements at the Proximal Phalanges in Healthy Women and Patients with Hip Fractures

Measurements of bone mineral density (BMD) are useful for the assessment of fracture risk in osteoporosis. First prospective studies showed that quantitative ultrasound as measured at the calcaneus also predicts future hip fracture risk, independently of BMD and as accurately as BMD. The aim of this study was to compile a reference population for a new ultrasound device that determines amplitude-dependent speed of sound (AD-SOS) through the proximal phalanges of the hand and to prove its ability to distinguish between health volunteers and osteoporotic patients. In a case–control study we examined 139 healthy women aged 21–94 years and a group of 24 female patients aged 69–94 years with recent hip fractures. In the healthy reference population additional BMD measurements were performed with dual-energy X-ray absorptiometry (DXA) and quantitative ultrasound measurements at the calcaneus were carried out. In vivo precision of AD-SOS measurements through the phalanges was 0.52% CV. Simple regression analyses showed a negative correlation with age (r= 70.73, p50.001); modest significant correlations with BMD of the lumbar spine (r= 0.36, p50.001) and BMD of the femoral neck (r= 0.37, p= 0.002) as measured with DXA were shown. The comparison with another ultrasound device measuring SOS and broadband ultrasound attenuation (BUA) through the calcaneus showed correlation with SOS (r= 0.50, p50.001); no significant correlation was found with BUA measurements. Furthermore a dependency of AD-SOS values in anthropometric factors such as body mass index (r= 0.37, p50.001), height (r= 0.40, p50.001) and weight (r= 0.23, p50.05) was shown. First study results on 24 clinically diagnosed osteoporotic patients, defined as patients with recent (51 week) pertrochanteric or femoral neck fractures, showed a good separation between age- and sex-matched controls and osteoporotic patients (Z= 72.0 SD). Receiver operating characteristic (ROC) curves showed an area under the fitted curve of 0.83 + 0.06. These results are powerful for a device measuring AD-SOS through the proximal phalanges of the hand, and further prospective studies have proven the capability of phalangeal ultrasound in fracture risk assessment. Received: 4 January 1996 / Accepted: 15 January 1998     

Quantitative Ultrasound and Symptomatic Vertebral Fracture Risk in Chinese Women

Quantitative ultrasound (QUS) is emerging as a simple, inexpensive and noninvasive method for assessing bone quality and assessing fracture risk. We assessed the usefulness of a contact calcaneal ultrasonometer by studying normal premenopausal women (group I, n= 53), normal postmenopausal women (group II, n= 198), and osteoporotic women without (group III, n= 141) and with vertebral fractures (group IV, n= 53). The osteoporotic subjects had a T-score of the spine or hip neck bone mineral density (BMD) <−2.5 based on the local Chinese peak young mean values. When compared with postmenopausal controls, mean broadband ultrasound attenuation (BUA), speed of sound (SOS), and quantitative ultrasound index (QUI) were 26%, 2.1% and 25% lower in women with vertebral fractures (p all <0.005). The correlation coefficients between QUS parameters and BMD of the spine and hip ranged between 0.4 and 0.5. The ability of the QUS to discriminate between patients groups was determined based on the mean value of normal premenopausal women in group I. The mean T-score for women with fractures was −2.87 ± 1.02 for BUA, −2.54 ± 0.79 for SOS, −3.17 ± 0.70 for QUI, −2.65 ± 0.86 for L2–4 BMD and −2.53 ± 0.66 for hip neck BMD. After adjustment for age and body mass index, the odds ratio of vertebral fracture was 1.71 (95% CI 1.2–2.6) for each 1 SD reduction in BUA, 2.72 (1.3–5.3) for SOS, 2.58 (1.4–4.6) for QUI, 2.33 (1.6–3.3) for L2–4 BMD, 2.09 (1.37–3.20) for femoral neck BMD and 1.88 (1.34–2.92) for total hip BMD. The association between the QUS parameters and vertebral fracture risk persisted even adjustment for BMD. The area under the receiver operating characteristic curve for BUA for vertebral fracture was 0.92, for SOS, QUI, L2–4 BMD and femoral neck BMD was 0.95, and for total hip was 0.91. Received: 7 January 1999 / Accepted: 18 May 1999     

Assessment of a New Quantitative Ultrasound Calcaneus Measurement: Precision and Discrimination of Hip Fractures in Elderly Women Compared with Dual X-ray Absorptiometry

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. Received: 29 October 1999 / Accepted: 7 September 1999     

Correlates of Quantitative Ultrasound in the Women’s Healthy Lifestyle Project

Quantitative ultrasound (QUS) assessment of bone is a strong predictor of hip fractures and is currently an FDA-approved tool to identify women at risk of osteoporosis. However, few studies have investigated the lifestyle and genetic correlates of QUS in women. This study investigated the cross-sectional associates of several lifestyle, demographic and genetic factors with calcaneal QUS parameters (broadband ultrasound attenuation (BUA) and speed of sound (SOS)) in 393 women aged 45–53 years. Leisure-time and historical physical activity, dietary calcium and protein, body composition, vitamin D receptor genotypes, menopause status, other health behaviors, calcaneal QUS parameters and bone mineral density (BMD) were assessed at a single clinic visit. Lean mass, recent physical activity and African-American race were the strongest correlates of SOS whereas dietary protein, calcium and recent physical activity were the strongest correlates of BUA. These predictors explained 13% and 6% of the variance in SOS and BUA, respectively. Smoking, alcohol intake, education, hormone replacement therapy, calcium and vitamin D supplements, historical physical activity and vitamin D receptor genotypes were not significantly associated with BUA or SOS. Lean body mass and premenopausal status were the strongest correlates of lumbar BMD whereas lean body mass, physical activity, African-American race and body mass index were significantly related to femoral neck BMD. Physical activity remained predictive of SOS after controlling for lumbar BMD. The spectrum and magnitude of risk factors for SOS and BUA, including lean body mass, physical activity, race, protein and calcium intake, parallel previously observed predictors of BMD. Received: 25 November 1998 / Accepted: 1 April 1999     

Site-Specific Bone Measurements in Patients with Ankle Fracture

Ankle fracture is one of the most common fractures in adults, particularly postmenopausal women. Few studies have examined the bone mineral density (BMD) and ultrasound properties of bone close to the site of fracture in patients with ankle fracture. The aim of this study was to evaluate these measurements in women with ankle fractures compared with controls. We studied 31 healthy post-menopausal women ages 50–79 years (mean age 63.2 ± 3.3 years) from a population-based group and 31 postmenopausal women ages 52–76 years (mean age 61.2 ± 2.2 years) with an ankle fracture. Distal tibia and fibula BMD were measured by dual-energy X-ray absorptiometry using the Hologic QDR 1000/W densitometer. In addition to total distal and tibia BMD, three subregions were automatically selected: ultradistal, middle and one-quarter regions. Speed of sound (SOS) and broadband ultrasound attenuation (BUA) of the calcaneus were measured using the Lunar Achilles+ (LA+) and CUBA Clinical (CC). In addition to SOS and BUA, LA+ Stiffness Index (SI) was also measured. The nondominant limb was measured in the population group and the contralateral limb in the ankle group. Differences between the groups were determined using t-tests. The ankle fracture group was heavier than the control group by an average of 10 kg. BMD measurements were therefore adjusted for weight. There were no significant differences between the ankle fracture and control groups in lumbar spine BMD, total or regional ankle BMD or calcaneal BUA. However, calcaneal SOS was decreased in the ankle fracture group when measured on the LA+ and CC by 50 m/s (–2.0 SD units, p<0.001) and 19 m/s (–0.5 SD units, p<0.01) respectively. LA+ SI was decreased in the ankle fracture group by 14 units (–1.1 SD units, p<0.001). In conclusion, ankle fracture is not a typical osteoporotic fracture. However, there may be structural changes in the bone (unrelated to bone density) which result in increased fragility and susceptibility to fracture. Received: 7 May 2001 / Accepted: 29 August 2001     

Influence of Physical Activity on Ultrasound and Dual-Energy X-ray Absorptiometry Bone Measurements in Peripubertal Girls: A Cross-Sectional Study

The aim of this cross-sectional study was to investigate whether two types of physical exercise affect the growing skeleton differently. We used calcaneal quantitative ultrasound measurements (QUS) and dual-energy X-ray absorptiometry (DXA) for measurement of bone mineral density (BMD), and to test how QUS values reflect the axial DXA values in these various study groups. A total of 184 peripubertal Caucasian girls aged 11–17 years (65 gymnasts, 63 runners, and 56 nonathletic controls) were studied. Weight, height, stage of puberty, years of training, and the amount of leisure-time physical activity were recorded. Broadband ultrasound attenuation (BUA) and sound of speed (SOS) through the calcaneus were measured. The BMD of the femoral neck and the lumbar spine were measured by DXA. The differences in mean values of bone measurements among each exercise group were more evident in pubertal than prepubertal girls. The mean BUA and SOS values of the pubertal gymnasts were 13.7% (77.8 dB/MHz versus 68.4 dB/MHz, P < 0.05) and 2.2% (1607.7 m/s versus 1572.4 m/s, P < 0.001) higher than of the controls, respectively. The mean BMD of the femoral neck in the pubertal gymnasts and runners was 20% (0.989 g/cm² versus 0.824 g/cm², P < 0.001) and 9.0% (0.901 g/cm² versus 0.824 g/cm², P < 0.05) higher than in the controls, respectively. The amount of physical activity correlated weakly but statistically significantly with all measured BMD and ultrasonographic values in the pubertal group (r = 0.19–0.35). The correlation between ultrasonographic parameters and BMD were weak, but significant among pubertal runners (r = 0.47–0.55) and controls (r = 0.39–0.42), whereas the DXA values of the femoral neck and the ultrasonographic parameters of the calcaneus did not correlate among highly physically active gymnasts. By stepwise regression analysis, physical activity accounted for much more of the variation in the DXA values than the ultrasonographic values. We conclude that the beneficial influence of exercise on bone status as measured by ultrasound and DXA was evident in these peripubertal girls. In highly active gymnasts the increase of the calcaneal ultrasonographic values did not reflect statistically significantly the BMD values of the femoral neck. Received: 28 June 1999 / Accepted: 2 November 1999     

Comparison of Quantitative Ultrasound Measurements in Calcaneus with DXA and SXA at Other Skeletal Sites: A Population-Based Study on 280 Children Aged 11–16 Years

We performed ultrasound measurements (QUS) of the calcaneus in a population-based setting on 280 healthy children, aged 11–16 years, from a small urban area in southern Sweden. The results are compared with dual-energy X-ray absorptiometry (DXA) measurements in the total body, the lumbar spine and the hip, as well as single-energy X-ray absorptiometry (SXA) of the forearm. Normative data and correlations between the three different techniques were determined. We found significant correlations between QUS and age (r= 0.34–0.54), height (r= 0.13–0.56) and weight (r= 0.30–0.60), and between QUS and bone mineral density (BMD) measurements (r= 0.44–0.70). Boys increased all their bone mineral variables with age, whereas girls showed a decreasing trend from age 15 years. QUS had a significantly higher increase in standardized value with age than Ward's triangle BMD, but a significantly lower increase in standardized value with age than distal radius (cortical site) BMD. At other BMD sites we did not find any significant differences compared with QUS regarding changes with age. The measurements obtained by QUS, DXA and SXA, respectively, were divided into quartiles. Of all subjects in the lowest quartile for QUS measurements, only 34–50% were also in the lowest quartiles for DXA and SXA measurements. In conclusion, QUS measurements of the calcaneus in children show similar results as for adult regarding the correlation with DXA and SXA; they also have a significant correlation with anthropometric data. QUS did not identify the same individuals with low bone mass as the X-ray techniques. Received: 23 June 1997 / Accepted: 21 January 1998     

Evaluation of a New Calcaneal Quantitative Ultrasound System and Determination of Normative Ultrasound Values in Southern Chinese Women

Quantitative ultrasound (QUS) assessment at the calcaneus has been found to be a safe and reliable method for evaluating skeletal status. The present study aimed at evaluating the precision of the Sahara bone ultrasound densitometer and to determine the normative QUS data in healthy southern Chinese women. Broadband ultrasound attenuation (BUA), speed of sound (SOS) and qualitative ultrasound index (QUI) were determined. The long-term in vitro precision of the Sahara machine over 6 months was 4.6% for BUA and 0.39% for SOS. The short-term in vivo precision was 3.2 ± 1.3% for BUA, 0.3 ± 0.2% for SOS and 1.8 ± 1.0% for QUI. The standardized precision for BUA, SOS and QUI was 4.4, 3.8 and 2.2 respectively. The normative data were determined in 1086 healthy subjects. Postmenopausal women had significantly lower BUA, SOS and QUI levels than the premenopausal women. Significant negative correlations were observed between QUS indices and age. Bone mineral density (BMD) assessments was performed on 349 of these subjects. BUA correlated significantly with lumbar spine BMD (r; = 0.326) and femoral neck BMD (r= 0.395). Similar correlations were observed between SOS, QUI and BMD, with r values ranging between 0.446 to 0.522. Despite the fact that Chinese women have significantly lower BMD values than Caucasian women, the mean BUA values for pre- and postmenopausal Chinese women (73 ± 18 and 59 ± 18 dB/MHz respectively) were almost the same as those reported for Caucasian womeo. These normative data will be useful in the assessment of southern Chinese women with fracture risk. Received: 7 May 1998 / Accepted: 18 August 1998     

Can the WHO Criteria for Diagnosing Osteoporosis be Applied to Calcaneal Quantitative Ultrasound?

With the increasing number of quantitative ultrasound (QUS) devices in use worldwide it is important to develop strategies for the clinical use of QUS. The aims of this study were to examine the age-dependence of T-scores and the prevalence of osteoporosis using the World Health Organization Study Group criteria for diagnosing osteoporosis and to examine the T-score threshold that would be appropriate to identify women at risk of osteoporosis using QUS. Two groups of women were studied: (i) 420 healthy women aged 20–79 years with no known risk factors associated with osteoporosis; (ii) 97 postmenopausal women with vertebral fractures. All subjects had dual-energy X-ray absorptiometry (DXA) measurements of the spine and hip and QUS measurements on three calcaneal ultrasound devices (Hologic Sahara, Hologic UBA575+, Osteometer DTUone). A subgroup of 102 (76 on the DTUone) healthy women aged 20–40 years was used to estimate the young adult mean and SD for each QUS and DXA measurement parameter to calculate T-scores. The age-related decline in T-scores for QUS measurement parameters was half the rate observed for the bone mineral density (BMD) measurements. The average T-score for a woman aged 65 years was –1.2 for QUS measurements and –1.75 for the BMD measurements. When osteoporosis was defined by a T-score ≤–2.5 the prevalence of osteoporosis in healthy postmenopausal women was 17%, 16% and 12% for lumbar spine, femoral neck and total hip BMD respectively. When the same definition was used for QUS measurements the prevalence of osteoporosis ranged from 2% to 8% depending on which ultrasound device and measurement parameter was used. Four different approaches, based on DXA-equivalent prevalence rates of osteoporosis, were utilized to examine which T-score threshold would be appropriate for identifying postmenopausal women at risk of osteoporosis using QUS measurements. These ranged from –1.05 to –2.12 depending upon the approach used to estimate the threshold and on which QUS device the measurements were performed, but all were significantly lower than the threshold of –2.5 used for BMD measurements. In conclusion, the WHO threshold of T=–2.5 for diagnosing osteoporosis requires modification when using QUS to assess skeletal status. For the three QUS devices used in this study, a T-score threshold of –1.80 would result in the same percentage of postmenopausal women classified as osteoporotic as the WHO threshold for BMD measurements. Corresponding T-score thresholds for individual measurement parameters on the two commercially available devices were –1.61, –1.94 and –1.90 for Sahara BUA, SOS and estimated heel BMD respectively and –1.45 and –2.10 for DTU BUA and SOS respectively Additional studies are needed to determine suitable T-score thresholds for other commercial QUS devices. Received: 25 June 1999 / Accepted: 29 September 1999     

Ultrasound Measurements at the Calcaneus in Men: Differences Between Healthy and Fractured Persons and the Influence of Age and Anthropometric Features on Ultrasound Parameters

The aim of this cross-sectional study was to assess the ability of quantitative ultrasound at the calcaneus to discriminate between fractured and unfractured men, fracture probability, and the relationship of ultrasonic parameters to age and body size. The study included 224 men (age range 36–86 years) with no history of diseases or therapy affecting bone metabolism. The subjects were divided into two groups (unfractured, n= 148; fractured, n= 76) matched for age and body size. Bone status was assessed by ultrasound measurements at the calcaneus. Long-term in vitro CV% values were 0.88% for speed of sound (SOS) and 0.54% for broadband ultrasound attenuation (BUA). In vivo CV% values were 0.33% for SOS and 2.48% for BUA, while sCV% values were 4.66% and 6.58%, respectively. The following SOS/BUA values were obtained: in unfractured men, SOS = 1517.5 ± 35.3 m/s and BUA = 114.0 ± 13.3 dB/MHz; in fractured men, SOS = 1492.6 ± 24.6 m/s and BUA = 106.1 ± 11.6 dB/MHz. The differences were significant (p<0.0001). The odds ratio for BUA for all fractures was 1.05 (95% CI, 0.03–2.07) and for SOS 2.13 (95% CI, 0.77–3.49). Only the age-related decrease in SOS in unfractured men was significant (r=−0.17, p<0.05). In fractured men, weight and body mass index (BMI) were found to correlate significantly with BUA (r= 0.31, p = 0.007, r= 0.31, p = 0.007, respectively). The areas under receiver operating characteristics (ROC) curves were 0.706 for SOS and 0.665 for BUA. Ultrasound measurements at the calcaneus thus enable discrimination between fractured and healthy males. Different patterns of the relationship between age and body size in the two groups suggest the presence of other, unknown factors affecting bone status. Their identification requires further prospective studies. Received: 2 February 1998 / Accepted: 23 October 1998     

Bone Mineral Density and Quantitative Ultrasound Parameters in Patients with Klinefelter’s Syndrome after Long-Term Testosterone Substitution

Klinefelter’s syndrome (KS) is a common sex chromosomal disorder associated with androgen deficiency and osteoporosis. Only few bone mineral density (BMD) and no quantitative ultrasound (QUS) data are available in these patients after long-term testosterone replacement therapy. We examined in a cross-sectional study 52 chromatin-positive KS patients aged 39.1 ± 12.4 years (mean ± SD). Patients had been treated with oral or parenteral androgens for 9.2 ± 8.2 years (range 1–32 years). Areal BMD and bone mineral apparent density (BMAD, i.e., estimated volumetric BMD) at the lumbar spine, total hip and femoral neck were determined by dual-energy X-ray absorptiometry. BMD T-scores in the patient group were calculated based on three different North American reference databases. The QUS parameters broadband ultrasound attenuation (BUA) and speed of sound (SOS) were measured at the calcaneus using an ultrasound imaging device (UBIS 3000) and were compared with QUS results in a sex-, age- and height-matched control group. QUS T-scores were calculated based on the results of QUS measurements in 50 normal Dutch men between the ages of 20 and 30 years. QUS and BMD results in the KS patient group were compared. Overall, based on the three reference databases, 46% and 63% of the KS patients had a T-score between −1 and −2.5 and a further 10% and 14% had a T-score ≤−2.5 at the total hip and/or lumbar spine, as measured by areal BMD or BMAD, respectively. Thirty-nine percent of the KS patients had a T-score between −2.5 and −1, while 2% had a T-score ≤−2.5 for BUA and/or SOS. BUA (77.7 ± 15.0 dB/MHz) and SOS (1518.8 ± 36.5 m/s) were significantly lower in the KS patients than in age- and height-matched controls (87.1 ± 17.8 dB/MHz, p<0.005, and 1536.5 ± 42.5 m/s, p<0.05). Correlation coefficients between the QUS parameters and areal BMD (0.28 to 0.37) or BMAD (0.27 to 0.46) were modest. ROC analysis showed that discrimination of a BMD or BMAD T-score ≤−2.5 with either BUA or SOS was not statistically significant.  Although a limitation of our study is that direct comparison of BMD and QUS T-scores is not possible because in the control group in which QUS parameters were determined no BMD measurements were performed, we conclude that despite long-term testosterone replacement therapy, a considerable percentage of patients with KS had a BMD T-score <−1 or even ≤−2.5, based on different North American reference databases. This percentage was even higher for BMAD. QUS parameters were also low in the KS patient group when compared with Dutch control subjects. QUS parameters cannot be used to predict BMD or BMAD in KS patients. Received: 28 February 2000 / Accepted: 3 August 2000     

Calcaneal Ultrasonometry: Response to Treatment in Comparison with Dual X-ray Absorptiometry Measurements of the Lumbar Spine and Femur

The object of this study was to determine the effectiveness of calcaneal ultrasonometry in the prediction of bone mineral changes in the lumbar spine and femoral neck in response to treatment of osteoporosis. There were 673 women in the study who had one or more follow-up measurements between 1 and 4 years after the initial baseline determination for a total of 881 same-day measurements of the calcaneus, spine, and femur. The LUNAR Achilles and LUNAR DPX (LUNAR Corporation, Madison, WI) were used. Patients were divided into three treatment time groups: Group 1, 1–<2 years, n = 461; Group 2, 2–<3 years, n = 278; Group 3, 3–<4 years, n = 142. There were significant increases in the bone mineral density (BMD) of the lumbar spine, femoral neck, and in the broadband ultrasonic attenuation (BUA) of the calcaneus for the three groups. In contrast, a significant decrease in speed of sound (SOS) was obtained in these time frames and the stiffness index remained unchanged. Spearmen correlations showed an inverse relationship between the percent changes in SOS and BUA, the reasons for which are speculative. Correlations between the percent changes in calcaneal parameters and the BMDs of the lumbar spine and femoral neck were weak, whether significant or not, rho varying from −0.12 to 0.20. There was a subset of 371 patient measurements that registered BMD increases in both the lumbar spine and femoral neck. This was considered to be an objective indication of adequate compliance with prescribed treatment. Analysis of this subset yielded parameter correlations similar to those of the entire group. It is concluded that changes in the calcaneal ultrasound parameters in response to treatment of osteoporosis are not a reflection of mineral changes occurring in the lumbar spine and femoral neck in a given individual, and in this regard, calcaneal ultrasonometry is not a substitute for direct-site dual X-ray absorptiometry (DXA) measurement of the lumbar spine and femur. Received: 19 February 1998 / Accepted: 24 June 1998     

Does the Combination of Quantitative Ultrasound and Dual-Energy X-Ray Absorptiometry Improve Fracture Discrimination?

The widespread availability of quantitative ultrasound (QUS) and X-ray absorptiometry densitometers raises the question of whether a combination of QUS and bone mineral density (BMD) measurements could provide a clinically useful method of enhancing the prediction of fracture risk. The aim of this study was to examine whether a combination of axial BMD and calcaneal QUS measurements can enhance fracture discrimination compared with either method alone. The study population consisted of 154 postmenopausal women with a history of atraumatic fracture at the spine, hip or forearm and 221 healthy postmenopausal women with no clinical risk factors for osteoporosis. Subjects had dual-energy X-ray absorptiometry (DXA) measurements of the lumbar spine (LS), femoral neck (FN) and total hip (THIP) and calcaneal broadband ultrasound attenuation (BUA) and speed of sound (SOS) measurements on the Hologic Sahara (SAH) and Osteometer DTUone (DTU). Z-scores were calculated using the mean and SD obtained from the healthy postmenopausal group. Logistic regression analysis yielded odds ratios for BMD measurements at the LS, FN and THIP of 2.2, 2.2 and 2.3, respectively. The odds ratios obtained for QUS measurements ranged from 2.5 for DTU BUA to 3.3 for SAH SOS. While these odds ratios for QUS measurements were higher than those obtained for BMD measurements, the differences were not statistically significant. When the odds ratios for QUS were adjusted for BMD at the spine and hip, the odds ratios remained significant in all cases indicating that QUS and BMD variables contribute independently to fracture discrimination. When the BMD-adjusted odds ratios were compared with those for QUS alone, they were slightly lower but not significantly so. When the QUS measurements were adjusted for THIP BMD, the odds ratios for QUS tended to be lower than when adjusted for LS and FN BMD. The Z-scores for each of the QUS measurement variables were combined with spine or hip Z-scores. Logistic regression analysis of the QUS and BMD combined Z-scores yielded slightly higher odds ratios of approximately 3.1 (compared with 2.9 obtained for QUS alone) and increases in the area under the curve of approximately 2%. However, these increases were not clinically significant. In conclusion, the combination of axial BMD and calcaneal QUS measurements did not significantly improve fracture discrimination compared with either method alone. Received: 29 June 2000 / Accepted: 18 December 2000     

Clinical Performance of a Highly Portable, Scanning Calcaneal Ultrasonometer

The aim of this study was to establish a normative database, assess precision, and evaluate the ability to identify women with low bone mass and to discriminate women with fracture from those without for a highly portable, scanning calcaneal ultrasonometer: the QUS-2. Fourteen hundred and one Caucasian women were recruited for the study. Among them were 794 healthy women 25–84 years of age evenly distributed per 10-year period to establish a normative database. Of these, 171 aged 25–34 years were defined as the young normal group for the purpose of T-score determination. Precision was assessed within 1 day (short-term) and over a 16-week period (long-term) in 79 women aged 25–84 years. Five hundred twenty-eight women ranging from 50 to 84 years of age with or without prevalent fractures of the spine, hip or forearm were measured to compare the QUS-2 with bone mineral density (BMD) of the hip and spine. Mean calcaneal broadband ultrasound attenuation (BUA) was constant in healthy women from 25 to 54 years of age and decreased with increasing age thereafter. Short-term precision, with and without repositioning of the heel, and long-term precision yielded comparable results (BUA SDs of 2.1–2.4 dB/MHz, coefficients of variations (CVs) of 2.5–2.9%). Calcaneal BUA was significantly correlated with BMD of the total hip (TH), femoral neck (FN) and lumbar spine (LS) in 698 women (r= 0.6–0.7, all p<0.0001). A similar relationship was observed for LS BMD compared with either TH or FN BMD (r= 0.7, p<0.0001). Prevalence of osteoporosis in our population (WHO criteria) was 20%, 17%, 21%, and 24% for BUA, BMD of the TH, FN and LS, respectively. Age-adjusted values for a 1 SD reduction in calcaneal BUA and TH and FN BMD predicted prevalent fractures of the spine, forearm, and hip with significant (p<0.05) odds ratios of 2.3, 2.0 and 2.1, respectively. Areas under the receiver operating characteristic curves for age-adjusted bone mass values predicting prevalent fracture were 0.62 for BUA, 0.59 for TH BMD, 0.60 for FN BMD, and 0.57 for LS BMD; all statistically equivalent. We conclude that the QUS-2 calcaneal ultrasonometer exhibits reproducible clinical performance that is similar to BMD of the spine and hip in identifying women with low bone mass and discriminating women with fracture from those without. Received: 19 July 2000 / Accepted: 6 December 2000     

A Comparison of the Longitudinal Changes in Quantitative Ultrasound with Dual-Energy X-ray Absorptiometry: The Four-Year Effects of Hormone Replacement Therapy

Quantitative ultrasound (QUS) has been proposed as a tool which can measure both the quantitative and qualitative aspects of bone tissue and can predict the future risk of osteoporotic fractures. However, the usefulness of QUS in long-term monitoring has yet to be defined. We studied a group of early postmenopausal women over a 4-year period. Thirty subjects were allocated to hormone replacement therapy and 30 selected as controls matched for age, years past the menopause (YPM) and bone mineral density (BMD) at the anteroposterior spine (AP spine). The mean age of the subjects was 52.4 years (SD 3.9 years), mean YPM 4.0 years (SD 3.2) and all subjects had a BMD T-score above −2.5 SD (number of standard units related to the young normal mean population). BMD was measured at baseline and annually by dual-energy X-ray absorptiometry (DXA) at the AP spine and total hip, and QUS carried out at the calcaneus, measuring broadband ultrasound attenuation (BUA), speed of sound (SOS) and Stiffness. Mean percentage changes from baseline were assessed at 2 and 4 years. The overall treatment effect (defined as the difference in percentage change between the two groups) was: AP spine BMD, 11.4%; total hip BMD, 7.4%; BUA, 6.4%; SOS, 1.1%; and Stiffness, 10.4% (p<0.01). To compare the long-term precision of the two techniques we calculated the Standardized Precision, which for QUS was approximately 2–3 times that of DXA, for a given rate of change. The ability of each site to monitor response to treatment was assessed by calculating the Treatment Response Index (Treatment Effect/Standardized Precision), which was: AP spine BMD, 10.4; total hip BMD, 3.9; BUA, 3.1; SOS, 0.3; and Stiffness, 4.2. This was then normalized for AP spine BMD (to compare the role of QUS against the current standard, AP Spine BMD), which was: total hip BMD, 0.38; BUA, 0.30; Stiffness, 0.40 (p<0.01); and SOS, 0.03 (NS). In summary, QUS parameters in the early menopause showed a similar rate of decline as AP spine BMD and total hip BMD measured by DXA. Hormone replacement therapy results in bone gain at the AP spine and total hip, and prevents loss in BUA and SOS measured by QUS at the calcaneus. QUS has a potential role in long-term monitoring, although presently the time period to follow individual subjects remains 2–3 times that for DXA, for a given rate of change. Anteroposterior spine remains the current optimal DXA monitoring site due to its greater rate of change and better long-term precision. Received: 20 January 1999 / Accepted: 14 June 1999     

Stiffness in Discrimination of Patients with Vertebral Fractures

We measured the ultrasound parameters of the heels of 49 women with vertebral fractures and 87 age-matched controls using an Achilles ultrasound device. Average broadband ultrasound attenuation (BUA), speed of sound (SOS) and Stiffness were significantly lower in fracture patients (p<0.0001). We also estimated the ultrasound parameters of patients compared with age-matched non-fracture controls and found the mean BUA to be −1.02 SD below control values. The mean SOS was −0.97 SD and the mean Stiffness was −1.12 SD below control values.  Femoral bone mineral density (BMD) at the neck, Ward’s triangle and the trochanter, the total-body BMD and L2–4 BMD were measured with dual-energy X-ray absorptiometry (DXA) and found to be significantly lower in fracture patients (p<0.0001). All correlation coefficients between ultrasound parameters and DXA measurements were >0.5 and statistically significant (p<0.0001). A stepwise logistic regression with presence or absence of vertebral fracture as the response variable and all ultrasound – DXA parameters as the explanatory variables indicated that the best predictor of fracture was Stiffness, with additional predictive ability provided by spine BMD. Sensitivity and specificity of all measures were determined by the areas under the receiver operating characteristic (ROC) curve, which were 0.76 ± 0.04 for BUA, 0.77 ± 0.04 for SOS, 0.78 ± 0.04 for Stiffness and 0.78 ± 0.03 for spine BMD. The areas under the ROC curves of BUA, SOS, Stiffness and spine BMD were compared and it was found that Stiffness and spine BMD were significantly better predictors of fracture than BUA and SOS. These results support many recent studies showing that ultrasound measurements of the os-calcis have diagnostic sensitivity comparable to DXA, and also demonstrated that Stiffness was a better predictor of fracture than spine BMD. Received: 23 September 1997 / Accepted: 10 April 1998