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     

An assessment of the use of quantitative ultrasound and the Osteoporosis Self-Assessment Tool for Asians in determining the risk of nonvertebral fracture in postmenopausal Chinese women

This cross-sectional study aims to assess the effectiveness of a simple, noninvasive scoring system, the Osteoporosis Self-Assessment Tool for Asians (OSTA), and quantitative bone ultrasound (QUS) in assessing nonvertebral fracture risk in Chinese postmenopausal women. A group of 513 community-dwelling women including 271 postmenopausal individuals participated in this study. Speed of sound (SOS m/s) at the radius, phalanx, and tibia were assessed by using the Omnisense prototype (Sunlight Ltd., Israel). Body height and weight were measured, and body mass index (BMI) and OSTA indices were calculated. Self-reported fractures were identified using a structured questionnaire. Phalanx SOS was significantly lower among postmenopausal women with a history of nonvertebral fracture occurred after menopause than those without (3755 m/s vs. 3841 m/s, P = 0.017, adjusted for age and weight), with an AUC of 0.66. The AUC of the OSTA for predicting nonvertebral fracture occurred after menopause was 0.64. SOS at the radius, phalanx, and tibia showed a positive correlation with OSTA index (r = 0.376–0.401, P < 0.001). The prevalence of nonvertebral fractures also increased significantly with the decreasing order of OSTA index (χ² = 5.432, P = 0.02). The OSTA values of ≤−1 and phalanx QUS T-score of ≤−1.95 can differentiate postmenopausal nonvertebral fracture with sensitivity of 75% and 81%, respectively, and specificity of 48% and 40%, respectively. Combining OSTA and phalanx QUS yielded a sensitivity of 83% and a specificity of 84% to detect postmenopausal nonvertebral fracture, with an AUC of 0.64. We conclude that OSTA and phalanx QUS are simple and effective clinical tools for identifying postmenopausal women at increased risk of nonvertebral fractures and can thereby facilitate the appropriate and more cost-effective use of bone densitometry to prevent osteoporotic fractures in developing countries.     

Ultrasound bone densitometry of Os calcis in elderly Japanese women with hip fracture

We evaluated 138 elderly patients (mean age 79 years) within 2 weeks after hip fracture (67 cervical and 71 trochanteric) using an Achilles ultrasound bone densitometer (Lunar Corporation, Madison, WI). The ultrasound variables of speed of sound (SOS in m/second), broadband ultrasound attenuation (BUA in dB/MHz), and stiffness (%) index were measured on the os calcis. Ultrasound densitometry also was done on 563 normal postmenopausal women to assess normal age changes. An elderly subgroup (n = 138) served as age-matched controls for the hip fracture group. Further subgroups of 33 patients and 33 controls were compared for lumbar spine and femoral neck BMD. There were no statistically significant differences between the hip fracture group and age-matched controls in height and weight, but each ultrasound variable was significantly lower for the hip fracture group (P < 0.0001). For the hip fracture group, SOS was 1470 ± 19 m/second, BUA was 84.3 ± 8.4 dB/MHz, and the stiffness index was 47.8 ± 9.2%, whereas for the age-matched controls, SOS was 1486 ± 27 m/second, BUA was 94.0 ± 11.4 dB/MHz, and the stiffness index was 59.1 ± 12.5%. There were no significant differences between cervical and trochanteric hip fracture groups. Logistic regression analysis showed that a change of the ultrasound values by 1 standard deviation (SD) changed the odds ratio for SOS, BUA, and stiffness index by 2.51, 3.24, and 3.60, respectively. Ultrasound variables, particularly stiffness, were good indicators of hip fracture risk. Received: 7 June 1995 / Accepted: 14 June 1996     

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     

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     

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     

Quantitative Ultrasound of the Calcaneus in Brazilian Caucasian Women: Normative Data Are Similar to the Manufacturer’s Normal Range

Quantitative ultrasound (QUS) can be a helpful alternative to identify osteoporotic patients. In this study we establish the QUS Brazilian normal range (BNR) and compare its values (means and standard deviations) with the manufacturer’s normal range (MNR). We measured three QUS parameters (broadband ultrasound attenuation, BUA; speed of sound, SOS; stiffness index, SI) at the right calcaneus in 352 healthy Caucasian Brazilian women, aged 20–84 years. We studied the age-dependent changes in QUS values and correlation with body size and years since menopause (YSM). A comparison of fracture risk classification using the BNR and MNR is also presented. Age was the most significant predictor for all QUS parameters (r=−0.49 for BUA, r=−0.66 for SOS, r=−0.64 for SI). Weight was accepted as the second determinant for BUA (final regression model: BUA = 101.3 − 0.282 × Age + 0.373 × Weight; p<0.001; adjusted R ²= 0.33). Body mass index (BMI) was accepted as the second predictor for SI (SI = 94.8 −0.595 × Age + 0.851 × BMI; p<0.001; adjusted R ²= 0.44). Height and YSM were accepted as second and third determinants for SOS values (SOS = 1718.7 − 1.147 × Age − 69.863 × Height − 0.521 × YSM; p<0.001; adjusted R ²= 0.45).There was a decline in SI of about 41% from the values in young adulthood to those of women in their eighties, about 76.4% of which occurred from age 45–49 years onward. Variation of mean SI with age from the BNR was consistent with the MNR in all but two 5-year age groups. In these two groups (50–54 years, p<0.01; 65–69 years, p<0.05), values derived from the BNR were 5.08% and 5.45% higher than the MNR values, respectively. Comparison of standard deviations in SI with age between the two populations did not show statistically significant differences. Using the fracture risk criteria proposed by the manufacturer, we observed that the MNR was appropriate for skeletal fragility evaluation in Brazilian women. Received: 8 November 1999 / Accepted: 26 April 2000     

Prediction of incident osteoporotic fractures in elderly women using the free estradiol index

A decline in postmenopausal estrogen concentration accelerates postmenopausal bone loss. We have examined the predictive power of endogenous estrogen production, DXA hip bone density (BMD), and heel quantitative ultrasound (QUS) on incident clinical fracture in a prospective 3-year population based, randomised controlled trial of calcium supplementation. Baseline blood testing on 1499 women mean (SD) age 75 (3) years for estradiol and sex hormone binding globulin measurements and ankle QUS measurements (Lunar Achilles) was undertaken. Bone density was measured using DXA (Hologic 4500A) at 1 year. Incident clinical fractures were confirmed by X-ray. At 3 years, 10% had sustained more than one incident fracture. The fracture group had significantly lower levels of free estradiol index (FEI) (0.40±0.44 versus 0.49±0.54 pmol/nmol), hip BMD (0.776±0.129 versus 0.815±0.124 g/cm²) and measures of QUS (BUA 98±8 versus 101±8 db/Hz, SOS 1504±22 versus 1514 ±26 m/s; stiffness 67±11 versus 71±11 % mean young adult), respectively, than the non-fracture group. After adjustment for age, weight, use of topical estrogen, calcium supplementation and prevalent fracture, incident fracture was predicted by free estradiol index (HR per SD: 1.43:95%CI: 1.08–1.91, P=0.013). After adjustment for BMD, SOS or stiffness, the free estradiol index no longer predicted fracture. When examined separately, the presence of a vertebral or an appendicular fracture was associated with an 18% lower free estradiol index compared with no fracture. The risk of vertebral fracture increased with decreased free estradiol index (HR per SD reduction: 1.63:95% CI: 0.91–2.92); the risk of appendicular fracture also increased with decreased free estradiol index (HR per SD reduction: 1.45:95% CI: 1.05–2.01) after adjustment for age, weight, use of topical estrogen, calcium supplementation and prevalent fracture. After further adjustment for hip BMD or QUS measures, the effect of free estradiol index was no longer significant for vertebral or appendicular fractures. Therefore, a low free estradiol index increases the probability of having an incident fracture as a result of decreased BMD. These data confirm the importance of postmenopausal estrogen concentration in the pathogenesis of osteoporosis in elderly women.     

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     

Ultrasound Measurement of Proximal Phalanges in a Normal Polish Female Population

In this cross-sectional study 954 Polish healthy women aged 30–80 years were evaluated (mean age 50.8 ± 8.9 years). Among them were 460 premenopausal (mean age 44.4 ± 5.5 years) and 494 postmenopausal women (mean age 56.8 ± 7.2 years). Women suffering from diseases known to affect bone metabolism and/or treated with drugs that affect bone tissue were excluded. All women were volunteers from six towns in the south of Poland, who underwent bone measurements for screening purposes. Bone status was assessed using an ultrasound device (DBM Sonic 1200, Igea, Italy) that measures amplitude-dependent speed of sound (AD-SoS) in metres per second. Phalanges (II–V) of the non-dominant hand were measured and an average value was computed. In vivo short-term precision was 0.49% for intraobserver, and 0.42% for interobserver measurements. Mean AD-SoS values were: in the whole group, 1974.6 ± 90.7 m/s; in premenopausal women, 2032.1 ± 50.0 m/s; and in postmenopausal women, 1921.0 ± 87.3 m/s (p <0.0001). The mean decrease in AD-SoS value in the studied population was 6.1 m/s per year. Simple linear regression analysis showed significant, negative correlations between age and AD-SoS: in the whole group r=– 0.70 (p <0.0001); in pre- and postmenopausal women, r=– 0.29 (p <0.0001) and r=– 0.58 (p <0.0001), respectively. Years since menopause (YSM) showed a significant influence on AD-SoS: linear correlation in the whole group resulted in a value of r=– 0.59 (p <0.0001) and in the group of postmenopausal women in a value of r=– 0.57 (p <0.0001). AD-SoS decreased in the first 8 YSM by 5.1% (0.63%/year) and in the next 15 YSM by 5.44% (0.36%/year). In postmenopausal women mean AD-SoS was regressed simultaneously on age and YSM, resulting in AD-SoS = 2181.0 – 4.031 6 Age – 3.911 6 YSM. In conclusion, ultrasound measurements of proximal phalanges were found to enable detection of age- and YSM-related skeletal changes in a Polish healthy female population. Results obtained in this study showed a premenopausal decrease in the ultrasound parameter (not observed by other authors) and an AD-SoS value lower than those in French, Italian and Spanish populations. The premenopausal decline in AD-SoS, the most important observation, requires further longitudinal investigations to determine factors affecting the skeleton before menopause. Received: 2 February 1997 / Accepted: 23 December 1997     

Metacarpal Radiogrammetry by Computed Radiography in Postmenopausal Women with Colles' Fracture and Vertebral Crush Fracture Syndrome

Based on the hypothesis that the underlying osteoporotic mechanism of Colles' fracture in postmenopausal women is similar to that of other osteoporotic fractures, that is, cortical bone resorption as opposed to cancellous bone resorption, the rate of corticoendosteal bone loss was compared in 40 normal postmenopausal women [average age 68.4 ± 7.1 years; 20 ± 4 years since menopause (YSM)], in 35 postmenopausal women with Colles' fracture (age 69.4 ± 7.5 years, 22 ± 8 YSM), in 35 normal postmenopausal women with vertebral crush fracture (age 69.4 ± 7.5 years, 22 ± 8 YSM, and in 35 normal premenopausal women (age 36.1 ± 7.9 years). Radiogrammetry by digital radiography of the second metacarpal was used to measure external (ED) and internal (ID) diameter, cortical thickness (CCT), cortical area (CA), and the ratio of cortical area to total area (CA/TA). The ID values of the groups of postmenopausal women were subtracted from the ID value of the premenopausal women and the result was divided by YSM to obtain the rate of corticoendosteal resorption/year (ΔC), CA resorption year (ΔCA) and CA/TA resorption/year (ΔCA/TA). ID, ΔC, ΔCA, and ΔCA/TA all were larger in the postmenopausal women with Colles' and vertebral crush fractures than in the normal postmenopausal women (ANOVA: all P < 0.0001). ID, CCT, ΔC, CA, ΔCA, and ΔCA/TA did not differ between the two groups of postmenopausal women with fractures. ΔC was 87% greater in postmenopausal women with vertebral crush fracture and 116% greater in women with Colles' fracture than in normal postmenopausal women. These results indicate that the loss of cortical bone is an important factor in Colles' fracture in postmenopausal women. Received: 10 October 1996 / Accepted: 15 October 1997     

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     

Ultrasound Measurements for the Prediction of Osteoporotic Fractures in Elderly People

In this prospective study we investigated the predictive value of quantitative ultrasound (QUS) measurements and other potential predictors of osteoporotic fractures in the elderly. During a 1-year period, 710 participants (132 men and 578 women), aged 70 years and older (mean age ± SD: 82.8 ± 5.9), were recruited from seven homes and apartment houses for the elderly. QUS measurements (broadband ultrasound attenuation (BUA) and speed of sound (SOS)) were assessed with a clinical bone densitometer. A structured questionnaire was used to collect information on other potential predictors. Follow-up of fractures was done each half year by telephone interviews. During the study period (median follow-up 2.8 years, maximum 3.7 years), 30 participants had a first hip fracture and 54 suffered from a first other nonspinal fracture. Cox regression analyses, adjusted for age and sex, showed that the relative risk (RR) of hip fracture for each standard deviation reduction was 2.3 (95% CI, 1.4–3.7) for BUA and 1.6 (95% CI, 1.1–2.3) for SOS. Slightly weaker relationships were found for any fracture (BUA: RR, 1.6; 95% CI, 1.2–2.1; SOS: RR, 1.3; 95% CI, 1.0–1.6). Multivariable analyses identified low BUA values and immobility as the strongest predictors for hip fractures and any fracture. Female gender proved to be the strongest predictor for other nonspinal fractures. It can be concluded that QUS measurements can predict the risk for hip fracture and any fracture in elderly people. Received: 23 July 1998 / Accepted: 19 November 1998     

Quantitative ultrasound of the os calcis in postmenopausal women with spine and hip fracture.

Quantitative ultrasonometry (QUS) of the os calcis has been shown to predict hip fracture in late postmenopausal women, and vertebral and forearm fracture in early postmenopausal women. Speed of sound (SOS), broadband ultrasound attenuation (BUA), and stiffness index (SI) of the os calcis were measured using the Achilles ultrasonometer (Lunar, Madison, WI). Osteoporosis risk factors were assessed by a detailed questionnaire. We examined 1314 normal women from age 48 to 79 yr, with a mean age 60 +/- 7.5 yr. In addition, we examined women of similar age, of whom 80 had suffered a hip fracture and 40 a spine fracture. The short-term precision in vivo expressed as the coefficient of variation was 1.2% for BUA, 0.2% for SOS, and 1.3% for SI. A total of 813 women were measured at both the right and left heel. There was high correlation between the two sides (r = 0.80-0.93) (p < 0.001), with no systematic offset. The ultrasound variables decreased significantly (p < 0.001) with age in healthy women; the annual decrease was -0.4% for BUA, -0.07% for SOS, and -0.7% for SI. BUA, SOS and SI discriminated (p < 0.001) between fracture and non-fracture subjects, but the fracture groups were 2 to 4 yr older. The T-score in the controls averaged -2.1 while that in the fracture patients averaged about -3.0. After control for age, years since menopause, and body size, BUA, SOS as well as the SI remained significantly lower (11 to 12% for SI) in women with fracture. The Z-score was -0.8 (p < 0.01) in spine fracture cases, and -0.9 (p < 0.001) in hip fracture patients. QUS provides a gradient of fracture risk comparable to X-ray densitometry of the axial skeleton, and gives comparable Z- and T-scores in younger postmenopausal women. It provides a precise, radiation-free, low-cost, and rapid method for fracture risk assessment in clinical practice.     

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     

Ultrasound velocity in the tibia in Japanese patients with hip fracture

 The speed of sound in the tibia (tibial SOS) was measured in elderly women to determine whether the tibial SOS declined with age, similarly to bone mineral density (BMD), as determined by dual-energy X-ray absorptiometry (DXA), and whether the tibial SOS in elderly hip fracture patients was lower than that in a control group. The subjects in this study included 38 female patients with hip fracture aged 65 years or more and 38 age-matched women living in a nursing home as the control group. There was a significant decline in the tibial SOS with age in women in the control group, but not in those with hip fracture. In all subjects aged under 80 years, the tibial SOS in women with hip fracture was significantly lower than that in women in the control group. In all subjects who were 80 years or older, the tibial SOS was not significantly different between women with hip fracture and the control group; thus, the tibial SOS in both groups was low, and they were considered to have progressive osteoporosis. The tibial ultrasound velocity can be expected to be useful as an indicator of the risk of limb fracture in the elderly. Received: February 25, 2002 / Accepted: June 4, 2002 Acknowledgments. We thank Omron Institute of Life Science Co., Ltd. for their support. Offprint requests to: S. Muraki     

Changes in bone mass and bone turnover following tibial shaft fracture

Introduction: Bone loss occurs in the regional bone following tibial shaft fracture. An earlier cross-sectional study showed that measurements made at the metaphyseal region of the tibia using peripheral quantitative computed tomography (pQCT) and the ultradistal region of the tibia using dual-energy X-ray absorptiometry (DXA) were the most responsive at monitoring this bone loss. Biochemical markers of bone turnover enable us to assess the activity of bone formation and resorption during fracture healing. The aim of this longitudinal study was to determine the pattern and distribution of bone loss and bone turnover following a tibial shaft fracture treated with either plaster cast or intramedullary nail. Methods: Eighteen subjects underwent bone mass measurements using DXA at the tibia and hip and quantitative ultrasound (QUS) at the tibia and calcaneus of both limbs at 2 weeks, 8 weeks, 12 weeks and 24 weeks following fracture, with hip and tibia DXA measurements also performed at 52 weeks. Nine of the patients treated with plaster cast had pQCT measurements at the tibia at 24 weeks. We measured three bone formation markers, bone alkaline phosphatase (bone ALP), osteocalcin (OC) and procollagen type 1 N-terminal peptide (PINP), a marker of bone resorption, serum C-telopeptides of type 1 collagen (β-CTX) and a marker of collagen III turnover, procollagen type III N-terminal peptide (PIIINP) at 1 day, 3 days and 7 days and at 2, 4, 8, 12, 16 and 24 weeks following fracture. The greatest bone losses were observed at the ultradistal region of the tibia using DXA (28%, p <0.001) and the metaphyseal region of the tibia using pQCT (26–31%, p <0.001) at 24 weeks. In the hip, the greatest loss was in the trochanter region at 24 weeks (10%, p <0.001). The greatest loss at the calcaneus measured using QUS was for broadband ultrasound attenuation (BUA) measured using CUBA Clinical at 24 weeks (13%, p =0.01). Results: At 1 year, there was a small recovery in bone loss (ultradistal tibia DXA, 20%, p <0.01; trochanter DXA 9%, p <0.001). Bone turnover increased following fracture (PINP +72±21%, p <0.0001, bone ALP +199±22%, p =0.004, β-CTX +105±23%, p <0.0001, all at 24 weeks). There was a smaller +33±10% increase in osteocalcin at 24 weeks. PIIINP concentration peaked at week 8 (+57±9%, p <0.0001). The bone resorption marker β-CTX showed an earlier rise (week 2, 139±33%) than the bone formation markers. Conclusions: We conclude that: (1) bone loss following tibial shaft fracture occurs both proximal and distal to the fracture; (2) the decreased BMD is largest for trabecular bone in the tibia with similar measurements using DXA and pQCT; (3) there is limited recovery of bone lost at the hip and tibia at 1 year; (4) tibial speed of sound (SOS) demonstrated a greater decrease than calcaneal SOS when comparing z -scores; (5) BUA is the QUS variable that shows the biggest decrease of bone mass at the calcaneus; (6) increase in bone turnover occurs following fracture with an earlier increase in bone resorption markers and a later rise in bone formation markers.     

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     

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     

Quantitative Ultrasound (QUS) of the Heel Predicts Wrist and Osteoporosis-Related Fractures in Women Age 45–75 Years

This study was designed to determine the ability of quantitative ultrasound (QUS) of the heel to predict fracture risk at different sites in postmenopausal women between the ages of 45 and 75 years. Heel QUS was measured at baseline using a Lunar Achilles scanner, and subsequent fractures were identified over 3 yr. The results were analyzed graphically after age adjustment and using Cox's proportional regression to estimate odds ratios for fracture risk; 3180 women were scanned (79% of sample). Sixty-three wrist, 12 hip, 4 vertebral, 7 proximal humerus, 3 pelvic, and 61 other fractures were identified over a mean followup of 31 mo. There was a fivefold difference in numbers of wrist and osteoporosis-related fractures (hip, vertebra, pelvis, and humerus combined) between the lowest and highest quartiles of QUS results adjusted for age. The odds ratios per 1 SD decline in QUS parameters adjusted for age were: wrist fractures BUA = 1.6, SOS = 1.5, stiffness = 1.8, osteoporosis-related fractures BUA = 1.9, speed of sound (SOS) = 1.6, stiffness = 2.2, and other fractures, BUA = 1.0, SOS = 1.1, stiffness = 1.1. When analyzed for each 10-yr age group, the odds ratios were generally higher in the 56-65 yr group than the other decades. In women between 45 and 75 yr, heel QUS can predict wrist and osteoporosis- related fractures at about the same level that dual-energy X-ray absorptiometry (DXA) of various sites can predict wrist fractures. This extends the current evidence that heel QUS can predict hip fracture risk in women over 75 yr to include other fracture sites in younger women. Heel QUS may be useful in the primary care assessment of osteoporotic fracture risk in women after the menopause.