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     

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     

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 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     

Comparison of broadband ultrasound attenuation to single X-ray absorptiometry measurements at the calcaneus in postmenopausal women

Broadband ultrasound attenuation (BUA), a radiation-free and portable technology, may be useful in assessing bone density and fracture risk. In this study, we compared cross-sectional BUA measurements to the more established single energy X-ray absorptiometry measurements of bone mineral density (BMD) at the calcaneus in 259 healthy postmenopausal women, aged 45–76 years. Paired measurements with repositioning of the subject's dominant heel were made consecutively by each method. A coefficient of variation (CV) for each method was calculated for each individual from the paired scans. BUA and BMD of the heel were also compared with BMD of the lumbar spine and femoral neck, as measured by dual energy X-ray absorptiometry. BUA was significantly correlated with BMD at the calcaneus (r=0.66, P<0.01). Heel BUA was also correlated with lumbar spine BMD (r=0.43, P<0.01) and femoral neck BMD (r=0.43, P<0.01) but the correlations were lower than those between heel BMD and spine (r=0.63, P<0.01) or femoral neck BMD (r=0.62, P<0.01). The mean CV for heel BUA (3.60±3.50%) was significantly greater than that for heel BMD (1.06±0.99%, P<0.01). The moderate correlation of calcaneal BUA and BMD, the lower correlations of BUA than heel BMD with both spine and hip BMD, and lower precision of BUA indicate BUA does not predict bone density as effectively as absorptiometry, the current standard methodology.The contents of this publication do not necessarily reflect the views or policies of the U.S. Department of Agriculture, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government.     

Leisure physical activity is associated with quantitative ultrasound measurements independently of bone mineral density in postmenopausal women

The purpose of this study was to assess the magnitude of the relationship between leisure physical activity and bone status as measured either by an Achilles^TM ultrasound bone densitometer (QUS) or dual-energy X-ray absorptiometry (DXA) in postmenopausal women. We studied 1162 French Canadian postmenopausal women, aged 33–84 years (mean age 58 years), for QUS parameters [broadband ultrasound attenuation (BUA), speed of sound (SOS), and stiffness index (SI)] measured at the right calcaneus, and bone mineral density (BMD) measured at the lumbar spine and femoral neck. Multivariate regression analyses revealed that leisure physical activity level was an independent predictor of the heel QUS parameters and of femoral neck BMD. No such association was observed for BMD of the lumbar spine. Heel QUS parameters (BUA, SOS, SI) and femoral neck BMD adjusted for interfering covariables showed a statistically significant difference between sedentary (less than three sessions/month) and active women (three or more sessions/week) (P 0.001). Furthermore, after adjusting each heel QUS parameters for the mean lumbar spine BMD value, the association observed between leisure physical activity and QUS remained significant. These results suggest that regular leisure physical activity could influence QUS parameters, independently of BMD, and that quantitative ultrasound could be a suitable outcome measure in exercise studies in postmenopausal women.     

Imaging Ultrasonometry of the Calcaneus: Optimum T-Score Thresholds for the Identification of Osteoporotic Subjects

The purpose of the present study was to (1) examine the age dependence of T-score results for calcaneal imaging ultrasonometry and dual X-ray absorptiometry of the axial skeleton and (2) determine the optimum T-score thresholds appropriate for broadband ultrasound attenuation (BUA) and speed of sound (SOS) measurements. A total of 453 healthy women aged 20-9 years were included in the study. All study participants underwent bone mineral density (BMD) measurements of the lumbar spine, femoral neck, total hip and calcaneal measurements of the BUA and SOS. An imaging ultrasound device (UBIS, DMS, France) was used for the ultrasound measurements. T-scores were calculated using a subgroup of 71 healthy women aged 20-35 years to estimate the mean value of young normals and SD for BUA, SOS, and BMD. The age-related decline in both BUA and SOS T-scores was slower than that in the equivalent figures obtained by BMD measurements. The optimum T-score thresholds estimated by receiver operating characteristic (ROC) analysis were 1.3 for BUA and 1.5 for SOS. Using the optimum threshold, the sensitivity and specificity for BUA was 68% and 83%, respectively. Corresponding values for SOS were 63% and 79%. Utilizing calculated optimum T score thresholds for BUA and SOS, the agreement among BUA, SOS, and BMD at the femoral neck was improved compared with that found using the T-score of < or = -2.5 criterion. In conclusion, the definition of osteoporosis by a T-score of , or = -2.5 was not applicable to imaging ultrasonometry of the calcaneus. Optimum T-score thresholds were determined for both BUA and SOS suitable to Ubis QUS device.     

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     

Reproducibility and Concordance in Quantitative Ultrasound Measurements Between Densitometers: A Comparative Study

Although calcaneal quantitative ultrasound (QUS) is an independent predictor of osteoporotic fracture, its role in monitoring changes in bone status remains limited because of its relatively poor precision compared to the rate of bone loss. Recently, imaging QUS has been developed that can standardize the region of interest in the calcaneus with the potential of improving precision. We assessed the concordance and precision of an imaging QUS scanner (UBIS 5000) and a nonimaging scanner (LUNAR Achilles+) in 52 subjects aged between 27 and 79 yr. Each subject had duplicate measurements on each scanner on the same day. The measurements were broad-band ultrasound attenuation (BUA), speed of sound (SOS), and stiffness index, which was derived from BUA and SOS. Precision was evaluated by the standard error of measurement (SEM) and within-subject coefficient of variation (CV). There was significant correlation between the two scanners in all QUS measurements (r > 0.8; p < 0.001); however, BUA and SOS measurements by the UBIS were significantly lower than by the Achilles+. The SEM of BUA (0.6 dB/MHz) and SOS (2.7 m/s) in the UBIS were significantly lower (p < 0.001) than the Achilles+ (1.4 dB/MHz for BUA and 6.3 m/s for SOS). When the SEM was expressed as the percentage of the mean, there were no significant differences in CVs between UBIS (0.9% for BUA and 0.2% for SOS) and Achilles+ (1.2% for BUA and 0.4% for SOS) scanners. The SEM of stiffness index derived by UBIS was not significantly different from that derived by the Achilles+. These data suggest that although there are systematic differences between the UBIS and Achilles+ scanners in QUS measurements, the precision of the two instruments is equivalent.     

Preliminary evaluation of a new ultrasound bone densitometer

Summary A new ultrasound bone densitometer has been developed that measures ultrasonic properties of the os calcis, namely, the speed of sound (SOS), broadband ultrasound attenuation (BUA), and a proprietary factor derived from SOS and BUA, termed stiffness. Short-term precision of ultrasound measurements was 1.4% for BUA, 0.2% for SOS, and 1.5% for stiffness in healthy women, and 1.1% for BUA, 0.1% for SOS, and 1.5% for stiffness in osteopenic women. One hundred seven women underwent measurements by ultrasound, together with dual energy X-ray absorptiometry (DXA) bone mineral density (BMD) measurements of the lumbar spine and proximal femur. Correlations between SOS, BUA, and stiffness measurements and DXA BMD measurements were all highly significant (P < 0.001) with r values varying from 0.54 to 0.67. BUA, SOS, and stiffness measurements were all significantly different between normal and osteopenic women even after adjusting for age, height, and weight (P < 0.05,P < 0.001, andP < 0.01, respectively). These results demonstrate that this ultrasound system measures ultrasonic properties of the os calcis with good precision, the measurements correlate moderately well with DXA BMD measurements and they can differentiate between normals and those with osteopenia.     

Effect of Region of Interest Location on Ultrasound Measurements of the Calcaneus

Ultrasound (US) measurements of the calcaneus are usually carried out in a region of interest (ROI) at a fixed site relative to a footplate. Recently, US transmission systems have been developed with imaging capability that enable selection of the position of ROI; the region of measurement is always the area of minimum attenuation in the posterior part of the calcaneus. This study compares measurements of broadband ultrasound attenuation (BUA) and speed of sound (SOS) at the variable ROI of minimum attenuation (ROI_v) and at fixed coordinates (ROI_f). Ultrasound variables were estimated at ROI_v and ROI_f in 212 female subjects, including 26 patients with osteoporotic fractures. Among the 186 women without fractures, 63 were classified as having osteoporosis on the basis of their vertebral bone density. Precision of BUA and SOS were better at ROI_v than at ROI_f. BUA was more highly correlated with bone mineral density (BMD) at the lumbar spine and femoral neck at ROI_v than ROI_f (r = 0.64 for lumbar spine and 0.68 for femoral neck at ROI_v versus 0.50 for lumbar spine and 0.54 for femoral neck at ROI_f, P < 0.05 for both comparisons). There were no significant differences between the correlations of SOS with axial BMD at ROI_v compared with ROI_f. Significant difference was found between the areas under the ROC curve for each ultrasound variable at ROI_v and ROI_f for both groups of patients, subjects with osteoporosis (area under curve = 0.87 for BUA at ROI_v versus 0.82 at ROI_f, P < 0.05; area under curve = 0.85 for SOS at ROI_v versus 0.81 at ROI_f, P < 0.05), and women with fractures (area under curve = 0.93 for BUA at ROI_v versus 0.86 at ROI_f, P < 0.05; area under curve = 0.91 for SOS at ROI_v versus 0.82 at ROI_f, P < 0.05). Ultrasound variables measured at ROI_v enable improved reproducibility and significantly better differentiation of diseased subjects from healthy individuals as compared with measurements at ROI_f. Received: 3 November 1997 / Accepted: 20 February 1998     

Bone mineral density in haemodialysis patients: A comparative study of dual-energy X-ray absorptiometry and quantitative ultrasound.

BACKGROUND: Quantitative ultrasound (QUS) of bone is a relatively new technique that appears to assess 'bone quality' in addition to bone mineral density. The purpose of this study was to evaluate the diagnostic potential of QUS of calcaneum and to correlate it with dual energy X-ray absorptiometry (DEXA) in chronic haemodialysis patients. METHODS: Broad-band ultrasound attenuation (BUA; dB/MHz) and speed of sound (SOS; m/s) of calcaneum and DEXA (g/cm(2)) measurements of the lumbar spine and hip were made in 39 patients. The indices obtained by either method were compared with age-and sex-matched controls. Calcaneal measurements were correlated to DEXA and relevant clinical and biochemical data of patients. RESULTS: BUA and SOS values were markedly reduced in dialysis patients compared to controls (59.1+/-13.8 vs 73.0+/-16.2 dB/MHz, P:<0.001 and 1533+/-28 vs 1560+/-29 m/s, P:=0.014 respectively). There was a moderate, but significant association between calcaneal parameters and DEXA (r=0.32-0.53, P:<0.05). Both BUA and SOS scores were inversely correlated with age (r=-0.69, P:<0.001) and duration of menopause (r=-0.74, P:<0.01). Additionally, BUA values showed a moderate negative association with serum intact parathyroid values (r=-0.38, P:=0.018). CONCLUSION: Chronic haemodialysis patients have reduced calcaneal BUA and SOS scores. QUS of the calcaneum is an easy-to-apply and radiation-free technique. It could be a useful substitute for assessment of bone density in such patients. However, further studies in large patient groups and comparisons with plasma markers of bone turnover and bone biopsy findings are needed to assess its potential place in the management of renal osteodystrophy.     

Imaging Ultrasonometry of the Calcaneus: Dependence on Calcaneal Area

The purpose of this study was (1) to investigate the dependence of broadband ultrasound attenuation (BUA) and speed of sound (SOS) measured in a circular region of interest (ROI) having a fixed size on calcaneal area and (2) to examine whether the normalization of ultrasonic variables for the area of the calcaneus provides better differentiation of diseased subjects from healthy individuals. Ultrasound variables were estimated in 169 healthy postmenopausal women (mean age 66.5 years, range 42–87 years) and 39 women with vertebral fractures (mean age 72.9 years, range 51–86 years). A minimum attenuation ROI, 15 mm in diameter, with a commercial imaging ultrasonometer was used. Significant relationships were found between both ultrasonic variables and calcaneal area (r²= 0.06, P < 0.001 for BUA, r²= 0.12, P < 0.0001 for SOS). Normalization of ultrasound variables (BUAn and SOSn) was based on the regression equations of the relationships among BUA, SOS, and calcaneal area. In a precision study, nine women were examined five times each to determine the errors arising from both the repositioning of the foot and selection of the calcaneal area. The reproducibility errors of BUA, SOS, BUAn, SOSn, and area were 0.87%, 0.20%, 1.07%, 0.27%, and 3.72%, respectively. Significant differences were found between the areas under the ROC curve for BUAn and BUA (area under the curve = 0.93 for BUAn versus 0.90 for BUA, P= 0.003) as well as for SOSn and SOS (area under the curve = 0.85 for SOSn versus 0.79 for SOS, P= 0.003). Normalization of ultrasound variables for calcaneal area improves the discrimination of clinical studies. Received: 7 June 1999 / Accepted: 18 January 2000     

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     

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     

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     

The relationship between bone mineral density and ultrasound in postmenopausal and osteoporotic women

The aim of this cross-sectional study was to use a novel method of data analysis to demonstrate that patients with osteoporosis have significantly lower ultrasound results in the heel after correcting for the effect of bone mineral density (BMD) measured in the spine or hip. Three groups of patients were studied: healthy early postmenopausal women, within 3 years of the menopause (n=104, 50%), healthy late postmenopausal women, more than 10 years from the menopause (n=75, 36%), and a group of women with osteoporosis as defined by WHO criteria (n=30, 14%). Broadband ultrasound attenuation (BUA), speed of sound (SOS) and Stiffness were measured using a Lunar Achilles heel machine, and BMD of the lumbar spine and left hip was measured using dual-energy X-ray absorptiometry (DXA). SOS, BUA and Stiffness were regressed against lumbar spine BMD and femoral BMD for all three groups combined. The correlation coefficients were in the range 0.52–0.58, in agreement with previously published work. Using a calculated ratio R, analysis of variance demonstrated that the ratio was significantly higher in the osteoporotic group compared with the other two groups. This implied that heel ultrasound values are proportionately lower in the osteoporotic group compared with the other two groups for an equivalent value of lumbar spine and femoral neck BMD. We conclude that postmenopausal bone loss is not associated with different ultasound values once lumbar spine or femoral neck BMD is taken into account. Ultrasound does not give additional information about patterns of bone loss in postmenopausal patients but is important in those patients with osteoporosis and fractures.     

Ultrasound measurements on os calcis: Precision and age-related changes in a normal female population

We performed ultrasound measurements in the calcaneus of 512 healthy women. Broadband ultrasonic attenuation (BUA) and speed of sound (SOS) were obtained with a Lunar Achilles ultrasonic instrument. Subjects studied were one group of 67 women working in our hospital (group A) and two groups which are part of two large prospective cohort studies (groups B and C). Group B consisted of 244 women aged 31–79 years randomly selected from a large insurance company, and group C consisted of 201 women aged 74–91 years randomly selected from the electoral rolls. Dual-energy X-ray absorptiometry (DXA) measurements of femoral neck and total body were performed with a Hologic QDR 2000 for group B and with a Lunar DPX Plus for group C. The in vitro precision of the Achilles, estimated by measuring a phantom daily for 45 days, was 0.84% for BUA and 0.12% for SOS. We assessed the in vivo short-term precision in 20 healthy volunteers working at the hospital, measured three times each. The coefficients of variation were 0.93% (±0.21) for BUA and 0.15% (±0.03) for SOS. The precision error was compared with the true variation, to obtain a standardized coefficient of variation. We analysed the three groups pooled together (n=512) and found for BUA an average 20% decrease and for SOS a 5% decrease between the ages of 20 and 90 years. We also performed separate analyses of subjects younger than 50 and older than 50 years, and within each 10-year age group we found that BUA was stable or slightly increased from 20 to 50 years and then decreased after 50. In contrast, SOS did not increase but decreased from the age of 20. We compared DXA measurements of the femoral neck and the total body with ultrasound measurements in groups B and C. In both groups the correlations were better with total body DXA than with femoral neck and spine DXA.     

Influence of Bone Quality on Precision of Calcaneal Ultrasonometry

This study was designed to determine the changes in precision of the ultrasound parameters speed of sound (SOS), broadband ultrasound attenuation (BUA), and stiffness index (SI) as a function of bone quality. The instrument used in this investigation was the LUNAR Achilles. Of the 608 female patients who had paired measurements with repositioning, 200 had t scores ≥−1 and 408 had t scores ≤−2.5, thus rendering a normal and a grossly abnormal group for comparison of precision results. It was found that the median precision error (CV%) for BUA was 1.99% for normal bone and 1.44% for abnormal bone (P= 0.02). No significant difference was obtained between median precision errors in normal and abnormal bone for the parameters SOS and SI, which were 0.23% and 0.19%, and 2.15% and 2.02%, respectively. In the interquartile range, the mean precision errors for SOS and BUA were significantly different in normal and abnormal bone: SOS was 0.25% and 0.21%, respectively, and BUA was 2.31% and 1.85%, respectively. No significant change was registered for SI. Precision error appears to decrease slightly at lower values for calcaneal variables. Received: 21 August 1996 / Accepted: 5 March 1997     

Mapping of Quantitative Ultrasound of the Calcaneus Bone to Chromosome 1 by Genome-Wide Linkage Analysis

Quantitative ultrasound (QUS) may predict the risk of fracture independent of bone density. The aim of this study was to identify, using quantitative trait linkage analysis, chromosomal regions that might contain genes influencing variation in calcaneal ultrasound measures in a set of families from the general population. A genome-wide autosomal scan was conducted in 324 Caucasian families (1270 measured individuals) from the Framingham Osteoporosis Study, using a set of 401 Marshfield microsatellite markers with a 10 cM average density map. QUS measurements included broadband ultrasound attenuation (BUA), speed of sound (SOS), and quantitative ultrasound index (QUI). These phenotypes were regressed on age, age², body mass index, height, alcohol and caffeine consumption, smoking status, physical activity, and estrogen use in females, in each sex and generation separately. Adjusted QUS phenotypes demonstrated a strong heritability ranging from 0.45 (SOS) to 0.52 (BUA). By two-point variance components genome screening, phenotype-specific regions of possible linkage were identified on chromosomal regions 1p36.3 and 5p15.2. The maximum LOD score attained was 2.74 for BUA with D1S468 (4 cM) and 2.69 for SOS with D5S817 (23 cM). QUI, a linear combination of the SOS and BUA, showed linkage with both markers (LOD = 2.1 with D1S468 and LOD = 2.2 with D5S817). Results of two-point analysis were confirmed by multipoint linkage analysis only for BUA, with LOD = 2.4 at D1S468, but not for SOS or QUI. The results for QUS, adjusted for femoral and lumbar spinal bone mineral density, in addition to the above covariates, were virtually the same. In conclusion, our results suggest that there may be genetic determinants for BUA on 1p36.3. These results should encourage further investigations of the genetic source of QUS variability and candidate polymorphisms in this region. Received: 7 March 2002 / Accepted: 14 May 2002