Do Markers of Bone Resorption Add to Bone Mineral Density and Ultrasonographic Heel Measurement for the Prediction of Hip Fracture in Elderly Women? The EPIDOS Prospective Study

We have previously shown that hip bone mineral density (BMD), heel broadband ultrasound attenuation (BUA) and bone resorption markers are independent predictors of hip fracture in elderly women. We investigated whether a combination of these three parameters could improve the predictive value of a single test in a nested case–control analysis (75 hip fractures and 228 age-matched controls) of the EPIDOS prospective study comprising 7598 healthy women 75 years of age and older followed prospectively for a mean 22 months. At baseline, prior fracture, femoral neck BMD by dual-energy X-ray absorptiometry (DXA), heel BUA and urinary type I collagen C-telopeptide breakdown products (CTX) were assessed. The area under the receiver operating characteristic curve was significant for the three diagnostic tests, heel BUA being the best single predictor. The added value of urinary CTX to either BMD or BUA depends on the cutoff point chosen to define patients at risk and on the therapeutic strategy that is considered. Defining patients at risk as those with low BMD (or low BUA) or high CTX resulted in a significant increase in the sensitivity compared with BMD or BUA alone – a strategy that could be applied when a broad treatment is considered. However, this increased sensitivity was also obtained simply by increasing the BMD and BUA cutoffs, suggesting that a combination of CTX with BMD/BUA is not useful for that type of treatment strategy. Conversely, defining patients at risk as those with both low BMD and high CTX increases the specificity (88% vs 78%) with a similar number of hip fracture patients being identified (30% vs 32%) – a combination that could be useful when the strategy is to target treatment to a subset of high-risk patients. This strategy appears to be more cost-effective than bone mass measurement alone as indicated by the 37% fewer patients who need to be treated to avoid one fracture per year. If DXA or ultrasound is not available, the combination of a bone resorption marker with a history of any type of fracture after the age of 50 years gave a predictive value similar to that obtained with femoral neck BMD or heel BUA alone, for both types of treatment strategy. We conclude that the combination of urinary CTX with hip BMD could be useful for the identification of elderly women at high risk for hip fracture, resulting in higher specificity for a given sensitivity threshold than BMD measurement alone. If DXA is not available, the combination of history of fracture and urinary CTX performs as well as hip BMD to assess hip fracture risk in elderly women. Received: 24 November 1997 / Revised: 3 March 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     

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     

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     

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     

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     

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 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     

Evaluation of a Hip Fracture Risk Score for Assessing Elderly Women: The Melton Osteoporotic Fracture (MOF) Study

Risk assessment for osteoporotic fracture within a primary care context, in old age, has received little attention. We aimed to develop such a risk score and assess its feasibility and validity. This was a 100% population-based, prospective cohort study, with a minimum 51/2 year follow-up among women aged 70 years and over, set in a large single general practice in Melton Mowbray, Leicestershire, UK. The main outcome measures were hip fracture, death and migration. Baseline measures included calcaneal broadband ultrasound attenuation (BUA), reported falls, balance, previous fracture history, medical problems, visual acuity, foot problems, body size, lifestyle factors and cognitive impairment. Seventy percent of the sample (1289) participated, including those in residential accommodation. Independent predictors of hip fracture over 3 years were low weight, kyphosis, poor circulation in the foot, epilepsy, short-term use of steroids and poor trunk maneuver. Using the highest tertile, a risk score based on these variables identified 84% (95% CI: 70% to 98%) of the hip fractures with a specificity of 68% (95% CI: 65% to 71%). BUA did not independently predict hip fracture in women of this age group. This study shows that a combination of readily obtained risk factors can identify elderly women who will sustain a hip fracture in the next 3 years more accurately than bone measurements alone in younger women. It also suggests that a risk score approach to universal assessment in the elderly is a feasible proposition in the primary care setting. Received: 15 January 2001 / Accepted: 5 September 2001     

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     

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     

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

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

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 of Bone in Male Osteoporosis

Quantitative ultrasound (QUS) measurement, a different approach to bone fragility assessment, has already been attempted in women with osteoporosis but rarely in men. In order to test its value and ability to identify osteoporotic men, a case–control prospective study was conducted using the Lunar Achilles, a device that measures attenuation and velocity parameters. Broadband ultrasound attenuation (BUA), speed of sound (SOS) and stiffness index (SI), a composite parameter, were assessed through the heel of 66 osteoporotic patients, and compared with the results in 35 controls. Patients had sustained a low-trauma fracture and/or had a lumbar and/or femoral bone mineral density (BMD) more than 2.5 SD below the young male reference value. As expected, all QUS parameters were statistically lower in patients, as were the dual-energy X-ray absorptiometry (DXA) measurements at the hip and lumbar spine. The two methods were compared for their ability to predict the risk of osteoporotic fractures. The odds ratios (ORs), with their 95% confidence limits, for fractures per 1 SD decrease were significant, especially for SOS and SI (OR = 2.3 [1.4–3.6] and 2.1 [1.3-3.3] respectively) and to a lesser extent for BUA (1.6 [1.0–2.4]). Our study suggests that QUS is associated with a history of low-trauma fracture in men; sensitivity is, however, less than when results are compared with BMD measurements (OR = 2.8 [1.6–5.0] and 3.4 [1.6–7.0] for lumbar spine and hip, respectively). Prospective studies are required before QUS can be recommended for clinical use in male osteoporosis. Received: 11 June 2001 / Accepted: 16 November 2001     

Femoral Neck and Intertrochanteric Fractures Have Different Risk Factors: A Prospective Study

The aim of this study was to determine whether both types of hip fracture, femoral neck and intertrochanteric, have similar risk factors. A prospective cohort study was carried out on community-dwelling elderly women in four areas of the United States: Baltimore, MD; Pittsburgh, PA; Minneapolis, MN and Portland, OR. The participants were 9704 Caucasian women, 65 years and older, of whom 279 had fractured their femoral neck and 222 had fractured their trochanteric region of the proximal femur. The predictors used were the bone mass of the calcaneus and proximal femur, anthropometry, history of fracture (family and personal), medication use, functional status, physical activity and visual function. The main outcome measures were femoral neck and intertrochanteric fractures occurring during an average of 8 years of follow-up. In multivariate proportional hazards models, several risk factors increased the risk of both types of hip fracture; including femoral neck bone density and increased functional difficulty. In hazard regression models that directly compared risk factors for the two types of hip fracture, calcaneal bone mineral density (BMD) predicted femoral neck fractures more strongly than intertrochanteric fractures (OR = 1.16; 95% CI = 1.02–1.31). Steroid use and impaired functional status also predicted femoral neck fractures instead of intertrochanteric fractures. Poor health status (OR = 0.74; 95% CI = 0.55–1.00) predicted intertrochanteric fractures more strongly than femoral neck fractures. We conclude that femoral neck fractures are largely predicted by BMD and poor functional ability while aging and poor health status predispose to intertrochanteric fractures. Received: 8 February 2000 / Accepted: 10 June 2000     

In Elderly Women Weight is the Best Predictor of a Very Low Bone Mineral Density: Evidence from the EPIDOS Study

Currently, few elderly women have a measurement of bone mineral density (BMD). The aim of this study was to assess the potential value of a two-step screening process to identify the elderly women who are at greatest risk of fracture because of very low BMD: (1) use simple clinical criteria to select women who are highly likely to have a very low BMD and (2) measure the BMD of the women so selected. We used baseline data from 6958 women aged 75 years or older who were participants in the EPIDOS prospective study of risk factors for hip fracture. The outcome variable was very low BMD measured at the femoral neck by dual-energy X-ray absorptiometry and defined as a T-score ≤−3.5. The factors most predictive of very low BMD were low weight, history of fracture after the age of 50 years, slow gait, balance impairment, low grip strength, and dependence for instrumental activities of daily living. A score based on the risk function including these factors has a sensitivity of 80% at the median cut-off. Hence, by measuring the BMD of only half the population, 80% of the women with very low BMD can be identified. Weight is the strongest determinant of very low BMD and has approximately the same sensitivity as the complete score. In conclusion, a risk score for very low BMD based on simple criteria such as weight could be a useful clinical tool to select elderly women for bone densitometry. Received: 13 July 1999 / Accepted: 19 April 2000     

Use of Clinical Risk Factors in Elderly Women with Low Bone Mineral Density to Identify Women at Higher Risk of Hip Fracture: The EPIDOS Prospective Study

Elderly women with very low bone mineral density (BMD) (T-score ≤−3.5) have a risk of hip fracture more than two times higher than the average risk of women of the same age. Using data from the EPIDOS prospective study, we have shown that by measuring BMD on the 50% of women who have the lowest weight, it is possible to identify the majority of these women at higher risk. In the present analysis, we assessed whether the use of clinical risk factors, in the subset of women selected for osteodensitometry and with moderately low BMD (T-score between −3.5 and −2.5), allows the identification of another subgroup of women with a risk 2 times higher than average and, thereby, increases the efficiency of selective BMD screening. We then assessed the discriminant value for hip fracture of the overall screening strategy (i.e., use of weight to select women for osteodensitometry, then use of clinical risk factors to enhance the predictive value of BMD), and compared it with the value of BMD used as a population screening tool. In total, 6933 EPIDOS participants, aged 75 years or above, were included in this analysis. Using Cox regression models, we first determined which baseline factors were most predictive of hip fracture among the 1588 women with weight below median (selection criteria for osteodensitometry in the proposed strategy) and T-score between −3.5 and −2.5. Based on the relative risk (RR) estimates from the final risk function, we calculated an individual risk score for hip fracture. We assessed the incidence of hip fracture for each value of the score, and determined the cutoff to identify women with a risk about 2 times higher than the average risk in this elderly cohort. The overall screening strategy (i.e., selective BMD measurement based on weight, followed by clinical fracture risk assessment) identifies two subgroups of higher risk women: a group with very low BMD (T-score ≤–3.5), and another group with moderately low BMD (T-score between –3.5 and –2.5) but a high fracture risk score. We calculated the total number of women classified as being at high risk, and assessed the overall sensitivity and specificity of this strategy to identify elderly women who will suffer a hip fracture. Among women with weight below median and T-score between −3.5 and −2.5, the factors most predictive of the risk of hip fracture were age, history of fall, ability to do the tandem walk (test of dynamic balance), gait speed and visual acuity. A simple additive score based on these factors (except visual acuity) allows a high-risk group (risk about 2 times higher than average) to be clearly distinguished from a low-risk group (risk below average). Overall, the proposed strategy identifies approximately 15% of the women in the cohort as being at high risk, i.e., 543 women with T-score ≤−3.5 and 503 women with −3.5 <T-score ≤−2.5 and a high fracture risk score. The sensitivity for hip fracture is equal to 37% and the specificity to 85%, which is equivalent to the discriminant value of BMD as a population screening tool. In elderly women, the use of a simple clinical risk score, in women with previous BMD values, allows the number of high-risk women identified to be increased. Overall, the proposed screening strategy (use of weight to select women for osteodensitometry, and then use of clinical risk factors to enhance the predictive value of BMD) has the same discriminant value for hip fracture as BMD used as a population screening tool. Received: 20 November 2001 / Accepted: 11 February 2002     

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