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     

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     

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     

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     

Differential Effects of Primary Hyperparathyroidism on Ultrasound Properties of Bone

Primary hyperparathyroidism (PHPT) may result in greater cortical than trabecular bone loss. Ultrasound is able to predict osteoporotic fracture risk independent of densitometric measurements, but little is known about the changes in ultrasound variables with PHPT. The aim of our study was to examine the effect of PHPT on ultrasound variables and bone density measurements at cortical (hand) and trabecular (lumbar spine and heel) sites, and to evaluate their reversibility following surgical treatment. We recruited 25 postmenopausal women diagnosed with PHPT ages 51–76 years (mean 62 years) and 95 postmenopausal controls ages 57–80 years (mean 67 years). Measurements were made at baseline and 1 year. Speed of sound (SOS) and broadband ultrasound attenuation (BUA) of the heel were measured using the Lunar Achilles (LA+) and McCue CUBA Clinical (CC). Amplitude-dependent speed of sound (AD-SoS) and ultrasound bone profile index (UBPI) of the fingers were measured using the IGEA DBM Sonic. Bone mineral density (BMD) of the hand and lumbar spine (LS) were measured by dual-energy X-ray absorptiometry (DXA). At baseline, hand BMD, LS BMD and heel BUA were significantly lower and finger UBPI significantly higher in the PHPT patients compared with controls (p<0.001). There were no differences in Stiffness Index, heel SOS or finger AD-SoS between control and PHPT subjects. At 1 year postoperatively, there was a mean (±SD) increase in LS and hand BMD of 3 ± 1% (p<0.01). BUA at the heel increased (11 ± 5%, p<0.001), and UBPI of the fingers decreased (17 ± 7%, p<0.001) probably reflecting different modes of attenuation in trabecular (scattering) and cortical (absorption) bone. Stiffness Index, SOS of the heel and AD-SoS of the fingers did not change. BUA, UBPI and BMD returned towards normal postmenopausal values following surgery. There were no changes in BMD or QUS variables at 1 year in the control group. Quantitative ultrasound (QUS) measurements provide different information about bone structure than densitometric measurements and cannot be regarded as simply reflecting bone density. With further research the combined use of BMD and QUS could improve the assessment of skeletal status in patients with PHPT before and after surgery. Received: 10 September 2001 / Accepted: 31 January 2002     

Heel Ultrasonography in Monitoring Alendronate Therapy: A Four-Year Longitudinal Study

The possibility of using quantitative ultrasound (QUS) in monitoring the response to antiresorptive drugs has yet to be defined. The aim of the present study was to evaluate whether heel ultrasonography, considering its characteristics of long-term precision, is able to monitor osteoporotic patients treated with alendronate. We studied 150 postmenopausal osteoporotic women (age 59.6 ± 5.3 years) treated with alendronate and calcium (n= 74) or with calcium alone (n= 76) for 4 years. At baseline and after 12, 24, 36 and 48 months, we measured bone mineral density (BMD) at the lumbar spine by dual-energy X-ray absorptiometry (DXA, Hologic 4500), and speed of sound (SOS), broadband ultrasound attenuation (BUA) and Stiffness at the calcaneus by Achilles plus. Moreover, the longitudinal precision of QUS parameters was assessed by measuring 10 subjects once a month for 1 year and, on the basis of the coefficients of variation we obtained, we calculated the Least Significant Change between two measurements. In the alendronate-treated patients, at year 1, BMD increased by 4.2%, SOS by 0.4%, BUA by 1.1% and Stiffness by 3.2%; at year 2, BMD increased by 5.0%, SOS by 0.7%, BUA by 1.4% and Stiffness by 5.7%. At year 3, BMD increased by 6.2%, SOS by 0.9%, BUA by 1.8% and Stiffness by 7.6%. At the end of the study period, BMD increased by 7.6%, SOS by 1.2%, BUA by 1.9% and Stiffness by 9.0%. The minimal significant difference between two measurements was 0.8% for SOS, 5.6% for BUA and 5.0% for Stiffness. Among the QUS parameters, Stiffness showed the greatest total treatment effect and a longitudinal sensitivity which was only slightly lower than BMD. The MTI, which represents the period between scans required to show that a ‘true’ change has occurred, was 1.8, 2.7, 11.9 and 2.2 years for BMD, SOS, BUA and Stiffness respectively. Therefore, although the spinal BMD remains the optimal method, QUS at the heel, and in particular Stiffness, seems to be a sensitive tool for monitoring the response to alendronate. Received: 30 August 2001 / Accepted: 29 November 2001     

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     

Multisite Quantitative Ultrasound: Precision, Age- and Menopause-Related Changes, Fracture Discrimination, and T-score Equivalence with Dual-Energy X-ray Absorptiometry

This study evaluated the clinical utility of a new multisite ultrasound device capable of measuring speed of sound (SOS) at the phalanx, radius, tibia and metatarsal. The in vitro and in vivo short- and long-term precision were evaluated, reference data were collected for 409 healthy white women (236 premenopausal and 173 postmenopausal), and age and menopause related changes were calculated using linear regression. Fracture discrimination was evaluated using 109 women with vertebral fractures and the age-adjusted odds ratios calculated for each standard deviation decrease in SOS measurement. Correlations between SOS measurements and spine and femur bone mineral density (BMD) were calculated. T-score equivalence with BMD was also investigated together with the prevalence of osteoporosis as defined by the WHO criteria. The in vivo short-term precision standardized in T-score units ranged from 0.14 to 0.33 and long-term standardized precision was 0.35–0.65. Postmenopausal age-related bone loss expressed as the annual change in T-score ranged from 0.040 to 0.089 for SOS and 0.053 to 0.066 for BMD, whilst menopause-related annual loss ranged from 0.036 to 0.094 for SOS and 0.050 to 0.074 for BMD. Correlations between the different SOS sites ranged from r= 0.24 to 0.55, and between SOS and BMD from r= 0.12 to 0.47. The odds ratio (and 95% confidence intervals) for fracture per 1 SD decrease in SOS were 2.0 (1.22 to 3.23) for the phalanx; 1.5 (1.01 to 2.24) for the metatarsal; 1.4 (1.03 to 1.99) for the radius and 1.2 (0.87 to 1.66) for the tibia. Odds ratios for BMD in the same population ranged from 2.6 to 4.8 (1.70 to 8.29). The prevalence of osteoporosis as defined by T= <–2.5 in the age range 60–69 ranged from 7.1% to 20.6% for SOS and 6.4% to 12.1% for BMD. In conclusion, this study demonstrated that multisite ultrasound has adequate precision for investigating skeletal status, is capable of differentiating between pre- and postmenopausal women and women with vertebral fractures, has a T-score equivalence similar to that of dual-energy X-ray absorptiometry (DXA), and appears to be a promising new technique for evaluating skeletal status at clinically relevant sites. Received: 11 August 2000 / Accepted: 14 December 2000     

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     

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     

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     

Ultrasound Measurement on the Calcaneus: Influence of Immersion Time and Rotation of the Foot

The aim of this study was to evaluate the influence of immersion time and rotation of the heel around the leg axis on the reproducibility of measurements using an ultrasound bone imaging scanner (UBIS) with a temperature-controlled water bath. Measurements were obtained in 10 men, 11 premenopausal women and 10 postmenopausal women. The right foot of all subjects was scanned 12 times with an interval of 3 min between each scan. The first 10 measurements, performed to study the effect of immersion time, were taken without intermediate repositioning. Measurements 11 and 12 were also taken without removing the foot, but the calcaneus position was varied by an angle of ±2.5° with respect to the reference position used during the first 10 measurements. Prolonged immersion of the heel led to a decrease in the variations of quantitative ultrasound (QUS) parameters between successive measurements. Following rapid variations with immersion time, the QUS parameters reached a plateau. The effect of immersion time on measurement error remained significant until the first two or three scans for broadband ultrasound attenuation (BUA) and until the sixth or seventh scans for speed of sound (SOS). The variation in BUA was more pronounced (p<0.05) for the group of postmenopausal women (20.7% change in BUA between the first and tenth scans; p<0.005) than for the group of premenopausal women (6.8% change in BUA between the first and tenth scans; p<0.005). The variations in SOS were similar in the two groups (0.8% variation; p<0.005). The impact of immersion time was smaller for men than for women [2.5%, (p<0.01) and 0.4% (p<0.005) of the change between the first and tenth scans for BUA and SOS respectively]. On the whole, the measurement errors due to rotation of the heel were lower than those caused by immersion time. The variations were significant only in men and premenopausal women. Both immersion time and rotation of the heel may play a role in the precision of QUS and should be carefully standardized, particularly for longitudinal studies. In addition, following these results we have adopted a standardized protocol to derive the technique reproducibility in groups of premenopausal and postmenopausal women. The coefficients of variation were 1.1% for BUA and 0.1% for SOS in premenopausal women, and 1.4% for BUA and 0.13% for SOS in postmenopausal women. Received: 17 February 1998 / Accepted: 1 September 1998     

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     

Quantitative Ultrasound Measurements of the Tibia and Calcaneus in Comparison with DXA Measurements at Various Skeletal Sites

The performance of quantitative ultrasound (QUS) measurements of the tibia and calcaneus was studied in 109 elderly people (age range 65–87 years). Broadband ultrasound attenuation (BUA) and speed of sound (SOS) were measured at the calcaneus and SOS was assessed at the tibia. Short-term precision of tibial QUS was studied in 16 volunteers. The coefficient of variation (CV) was 0.4% and the standardized CV (sCV) was 4.4%. We compared the calcaneal and tibial QUS measurements with bone mineral density (BMD) measurements of the lumbar spine, femoral neck, trochanter and total body assessed by dual-energy X-ray absorptiometry (DXA). Calcaneal QUS correlated better with BMD at various skeletal sites than tibial QUS. Calcaneal BUA showed higher correlations with BMD values of the lumbar spine, femoral neck, trochanter and total body than calcaneal and tibial SOS (r= 0.48–0.64, r= 0.30–0.47, r= 0.35–0.47, respectively; p<0.001). Body weight modified the relationships between calcaneal and tibial QUS and BMD measurements of the hip. Higher body weight was associated with higher BMD values at the femoral neck and trochanter for the same calcaneal and tibial QUS values. After adjustments for body weight correlations of tibial and calcaneal QUS with BMD improved and were very similar. This suggests that correction for body weight is important and could add to the predictive value of QUS measurements. Received: 16 July 1997 / Accepted: 8 July 1998     

Precision of Quantitative Ultrasound Measurement of the Heel Bone and Effects of Ambient Temperature on the Parameters

The goal of this study was to determine the magnitude of measurement error of a quantitative ultrasound (QUS) measurement system of the heel bone in a practical setting and to examine the effects of ambient temperature in the test room on QUS parameters. We assessed the intratest, intertest and interdevice coefficients of variation (CVs) for speed of sound (SOS), broadband ultrasound attenuation (BUA) and stiffness in vitro using phantoms and in vivo using volunteers. The intratest CV was the smallest and the interdevice CV was the greatest for every QUS parameter. The intertest CVs in vivo were 0.50% for SOS, 2.53% for BUA and 4.38% for stiffness. The standardized precision error (sPE) of stiffness, however, was smaller than those of the other two parameters. The intertest sPEs in vivo of the QUS parameters were 2–3 times greater than that of the spine bone mineral density (BMD) as measured by dual-energy X-ray absorptiometry (DXA). Using an average of duplicate measurements for the representative value of a subject could improve sPE of the QUS parameters to around 2 times greater than that of spine BMD. We examined five phantoms each with the QUS system under the ambient temperature conditions of 10, 20 and 30 °C. The lower the room temperature, the greater the values of all the QUS parameters obtained. We then assessed the effect of the season on the QUS parameters in healthy five women. SOS and stiffness were significantly greater in February (room temperature, 12.6 °C) than in June (22.4 °C) by 0.74% and 3.2% of overall means, respectively, by 10.1% and 4.3% as a standardized difference, or by 0.422 and 0.214 in Z-scores. This difference was likely to be caused by the difference in heel temperature between the seasons. The precision of the QUS system was inferior to that of conventional DXA densitometry. We recommend that institutions using several QUS system devices throughout the year at various locations monitor the precision of each device, make duplicate measurements for a single subject, use the same device for each patient being followed, and control the heel temperature of subjects by keeping the test room temperature constant throughout the year. Received: 15 October 1998 / Accepted: 19 May 1999     

Quantitative Heel Ultrasound in 3180 Women Between 45 and 75 Years of Age: Compliance, Normal Ranges and Relationship to Fracture History

There is growing evidence to support the use of quantitative ultrasound (QUS) to identify fracture risk in late postmenopausal women but few data are available in younger women. In order to address this issue all women between 45 and 75 years of age registered in two general practices in Bournemouth, Dorset, UK were invited to attend for heel QUS. Measurements were made in 79% of the 4018 women identified. The mean QUS results for 5-year age groups were very similar to those from reported reference ranges from North America and the north of England. The odds ratios (95% confidence limits) for self-reported fractures after 45 years per standard deviation of age-adjusted QUS parameters were: broadband ultrasound attenuation (BUA) = 1.40 (1.26–1.56), speed of sound (SOS) = 1.56 (1.41–1.74) and Stiffness = 1.52 (1.37–1.68). The results suggest that QUS is associated with fracture history in early postmenopausal women. Received: 11 March 1997 / Accepted: 12 October 1997     

Quantitative Ultrasound Calcaneus Measurements: Normative Data and Precision in the Spanish Population

Quantitative ultrasound (QUS) assessment at the calcaneus has been found to be a safe and reliable method for evaluating skeletal status. In this study we have determined the normative QUS data in the Spanish population for the Sahara Clinical Sonometer (Hologic). Broadband ultrasound attenuation (BUA), speed of sound (SOS), quantitative ultrasound index (QUI) and estimated bone mineral density (BMD) were determined. We also studied the precision in vivo and in vitro. The short-term in vivo precision (CV) was 4.88% for BUA, 0.36% for SOS, 3.45% for QUI and 4.15% for BMD, while in vitro precision was 0.40% for SOS and 2.67% for BUA. Our results are comparable to reference population data previously published in other countries and may serve as reference normative data for both genders in Spain. Received: 9 November 2001 / Accepted: 3 January 2002     

Age Changes of Calcaneal Ultrasonometry in Healthy German Women

This study assessed age changes in quantitative ultrasound sonometry (QUS) in a large sample of healthy German women. Speed of sound (SOS), broadband ultrasound attenuation (BUA), and stiffness index (SI) of the calcaneus were measured in 1333 women (mean age 50.5 ± 11.5 years) using the Achilles ultrasonometer (Lunar Corp., Madison, WI, USA). The short-term precision in 31 adults was 0.2% for SOS, 1.2% for BUA, and 1.3% for SI. There was an overall decline of 15% for BUA, 4% for SOS, and 31% for SI between late adolescence and old age. In premenopausal women, BUA decreased only slightly (−3%), whereas postmenopausal women showed a significantly increased decline (−12%). In contrast, SOS continuously decreased from the age of 15; there was a decline of 2% from adolescence to the menopause; postmenopausal women showed a slightly larger decline (−2.5%). The SI of premenopausal women decreased by 10%, but the postmenopausal decline of almost 22% was significantly greater. SI values for premenopausal German women were comparable to those observed in the American Achilles reference population, but postmenopausal German women had significantly higher SI values of 7% due to a lower rate of aging loss. Received: 12 August 1998 / Accepted: 28 January 1999     

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     

A Clinical Prediction Rule to Identify Premenopausal Women with Low Bone Mass

Identifying premenopausal women at risk for osteoporosis and related fractures is a potentially important way to reduce the burden of illness from this disease as low peak bone mass is a risk factor for postmenopausal osteoporosis. We examined predictors of ‘low’ peak bone mass in 668 healthy, pre-menopausal, Caucasian women ages 18–35 years. Predictors of bone mass were assessed using a detailed, standardized interview. Bone mass was assessed using two measures: dual-energy X-ray absorptiometry (DXA) at the femoral neck and lumbar spine, and quantitative ultrasound (QUS) of the heel, which evaluates stiffness, speed of sound (SOS) and broadband ultrasound attenuation (BUA). Bone mass was considered ‘low’ if the corresponding Z-score was <–1.00 (DXA values, stiffness) or if values were in the lowest quintile (BUA, SOS). Using multivariate logistic regression modeling, predictors of low bone mass based on QUS, DXA or both were determined. The mean age of the cohort was 27.3 years. Independent predictors of low bone mass by both DXA and QUS were: low body weight, menarche at age 15 years or later and physical inactivity as an adolescent. Individuals with all three risk factors had a 92% chance of having low bone mass using both techniques. This suggests that a simple risk factor assessment can identify most young women with low peak bone mass. Early intervention in this group of women may reduce the risk for osteoporosis in later life. Received: 2 June 2000 / Accepted: 20 November 2001