Changes in QUS and BMD Measurements with Antiresorptive Therapy: A Two-Year Longitudinal Study

There is lack of consensus on whether quantitative ultrasound (QUS) measurements can be used to monitor response to therapy. The aim of this 2-year longitudinal study was to assess whether calcaneal QUS measurement variables respond to antiresorptive therapy and whether these measurements display adequate long-term precision to be useful for monitoring purposes. The study population consisted of 195 postmenopausal women divided into three groups: Group 1: 39 women treated with antiresorptive therapy who commenced treatment at baseline; Group 2: 25 women treated with antiresorptive therapy who had been on treatment for at least 2 years at baseline; Group 3: 131 women who did not taken estrogen, bisphosphonates, or calcium during the 2-year study period. Subjects had baseline and 12 and 24 months follow-up BMD measurements at the lumbar spine (LS), femoral neck (FN), and total hip (THIP) and calcaneal QUS measurements of broadband ultrasound attenuation (BUA) and speed of sound (SOS). BUA and SOS were combined to provide an estimate of heel BMD (Est heel BMD). For women in Group 1, all BMD and QUS measurement variables increased significantly from baseline after 2 years of treatment. For women in Group 2, only THIP BMD and BUA increased significantly after 2 years and the changes were less than those observed in Group 1 women. The overall treatment effect for each measurement variable, defined as the difference in the mean absolute changes between Groups I and 3 after 2 years, was 0.08, 0.03, and 0.04 g/cm2 for LS, FN, and THIP BMD, and for BUA, SOS, and Est heel BMD it was 5.8 dB/MHz, 13.1 m/sec, and 0.05 g/cm2, respectively. When the overall treatment effect was expressed in T-score units, the effect was greatest for LS BMD (0.65 T-score units) and lowest for FN BMD (0.31 T-score units). QUS measurement variables yielded intermediate values of 0.43- 0.52 T-score units. The average least significant change (LSC) was 0.38 T-score units for BMD measurements, whereas the LSC for QUS measurements was three times greater at approximately 1.20 T-score units. Ninety-four percent of the women in Group 1 showed changes in LS BMD that exceeded the LSC after two years, while the percentage was lower for the other measurement variables ranging from approximately 6% for FN BMD, SOS and Est heel BMD to 50% for THIP BMD. A lower percentage of women in Groups 2 and 3 displayed changes that exceeded the LSC for both BMD and QUS measurement variables. Changes in all QUS variables were significantly correlated with changes in LS BMD, with correlation coefficients ranging from 0.26 to 0.40. In conclusion, calcaneal QUS measurement variables were found to show a highly significant response to antiresorptive therapy. However, the precision of QUS measurements was not good enough to allow QUS to be used for monitoring response to treatment. Future improvements in the precision of calcaneal QUS measurements are required to increase the utility of QUS for monitoring purposes.     

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     

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     

Bone mineral density (BMD) assessment of central skeletal sites from peripheral BMD and ultrasonographic measurements: an improved solution employing age and weight in type 3 regression.

The objective of this study was to develop a method whereby bone mineral density measurements of the heel and finger, as well as ultrasonographic measurements of calcaneal sound transmission, could identify individuals with a diagnosis of osteoporosis or osteopenia by the World Health Organization criteria for these diagnoses in the central skeleton (i.e., the lumbar spine (LS) and hip [femoral neck] [FN]). Two hundred and forty-four women in a university hospital laboratory setting had dual-energy X-ray absorptiometry measurements of bone mineral density (BMD) in the calcaneus, finger, hip, and spine, and quantitative ultrasound of the calcaneus. Regression equations were developed to predict central bone mineral T-scores from T-scores of peripheral measurements, adjusted by age and weight. Equations were validated by predicting the cut point for osteopenia at the lumbar spine and hip (T-score=-1.0). Ninety-five percent confidence intervals of the mean predicted LS or FN T-score from each peripheral site included -1.0. We conclude that our derived regression equations (taking into account interaction of peripheral BMD with patient age and weight) are useful for predicting T-scores in the central skeleton. This approach reduces the potential for misdiagnosis, which can result if one uses unadjusted peripheral T-scores, which are only moderately correlated with the central measurements of BMD.     

Does Quantitative Ultrasound Imaging Enhance Precision and Discrimination?

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

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

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

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     

Age, gender, and fragility fractures are associated with differences in quantitative ultrasound independent of bone mineral density

Bone strength is determined by bone mineral density (BMD) and bone structure. Dual-energy X-ray absorptiometry (DXA) measures BMD. Whether quantitative ultrasound (qUS) measures a property of bone distinct from BMD is uncertain. To evaluate this, DXA and qUS were measured in 58 fracture patients and 428 controls. To study the independent effects of age and gender on qUS measurements and control for BMD by study design rather than statistical methods, subgroups from the normative database were created and intentionally matched by the same femoral neck (FN) BMD. Speed of sound (SOS; m/sec), broadband ultrasound attenuation (BUA; dB/MHz), and stiffness index (SI) were then compared in individuals matched by FN BMD but differing in age, gender, and presence or absence of fractures. The results are presented as percentage difference (mean +/- SD). Elderly women with the same FN BMD as young women had 1 +/- 2% lower SOS (p < 0.05), 8 +/- 15% lower SI (p < 0.05), and 4 +/- 9% lower BUA (p = 0.07). Elderly women with the same FN BMD as elderly men had 5 +/- 9% lower BUA (p < 0.05). Elderly men with the same FN BMD as young men had 1 +/- 2% lower SOS (p = 0.1), 5 +/- 14% lower SI (p = 0.2), and 1 +/- 9% lower BUA (n.s.). Young women with the same FN BMD as young men had 2 +/- 7% lower BUA (n.s.). Women with fragility fractures had 8 +/- 11% lower BUA (p < 0.001) and 13 +/- 22% lower SI (p < 0.01) than controls with no fractures matched by FN BMD, age, and gender. Men with fragility fractures had 13 +/- 12% lower BUA (p < 0.01) and 16 +/- 19% lower SI (p < 0.05) than controls with no fractures matched by FN BMD, age, and gender. Despite comparable femoral neck BMD, qUS measurements differed according to age, gender, and fracture status, suggesting that qUS may provide additional information independent of femoral neck BMD, such as differences in connectivity or other properties yet to be identified.     

Calcaneal ultrasound predicts early postmenopausal fractures as well as axial BMD. A prospective study of 422 women

Low calcaneal ultrasound measurement (quantitative ultrasound, QUS) has been shown to predict fractures in elderly women. However, only a few studies have examined its ability to predict perimenopausal and early postmenopausal fractures. We conducted a prospective population-based cohort study to assess the capability of QUS as compared to axial BMD measurement to predict early postmenopausal fractures at that age. Four hundred and twenty-two women (mean age 59.6, range 53.7–65.3) from the Kuopio Osteoporosis Risk Factor and Prevention Study (OSTPRE) were randomly chosen to undergo a calcaneal ultrasound measurement. In all, 9.4% of these women were premenopausal at the time of measurement. Thirty-two follow-up fractures were reported during the mean follow-up of 2.6 years (SD 0.7). These were validated with patient record perusal. Broadband ultrasound attenuation (BUA), speed of sound (SOS) and stiffness index (SI) were significantly lower among women with than without fracture (P-values 0.028, 0.001 and 0.001, respectively). Mean T-score adapted from SI was –1.5 (95% CI –1.7 to –1.2) for fracture group and –1.0 (95% CI –1.1 to –0.9) for the non-fracture group. All QUS measurements predicted fractures even after adjusting for age, weight, height, previous fracture history, femoral neck BMD and use of hormone replacement therapy according to Cox regression. The adjusted hazard ratios (HR, 95% confidence interval) of a follow-up fracture for a 1 SD decrease were 1.80 (1.27–2.56), 1.72 (1.21–2.45) and 1.43 (1.01–2.03) for SOS, SI and BUA, respectively. Similarly, the adjusted HR for a 1 SD decrease of spinal BMD was 1.27 (0.85–1.94) and for that of femoral neck BMD 1.14 (0.78–1.70). In receiver operator analyses, the area under the curve (AUC) was greatest for QUS measurements: SOS (AUC=0.68), stiffness (AUC=0.67), BUA (AUC=0.62) and least for lumbar BMD (AUC=0.56), while and femoral neck BMD (AUC=0.59). The difference between AUCs was statistically significant between SI and lumbar BMD (P=0.02, Duncans P=0.07). We conclude that low calcaneal QUS predicts early postmenopausal fractures as well as or even better than axial BMD.     

Quantitative ultrasound assessment of bone in patients with primary hyperparathyroidism

Quantitative ultrasound measurements were done in a group of 26 patients (4 males and 22 females, aged 55.4 ±14.2 years) with primary hyperparathyroidism, and the results were compared with bone mineral density (BMD) carried out at various skeletal sites. Speed of sound (SOS), broadband ultrasound attenuation (BUA), and stiffness were measured with the Achilles ultrasound bone densitometer (Lunar Corp., Madison, WI). Mean ± SD values of SOS, BUA and stiffness in patients with primary hyperparathyroidism were 1522±38 m/seconds, 111±16 dB/MHz, and 80.4±19.8%, respectively. There were significant differences of mean T-score BUA values (-0.63±1.11) compared with corresponding T-score BMD values found at ultradistal (-1.85±1.73, P<0.01), proximal radius (-2.40±2.13, P<0.001), and total femoral (-1.60±1.32, P<0.001) sites. Correlation coefficients between both SOS and BUA values with BMD measurements at specific skeletal sites varied, but stiffness correlated moderately (0.6–0.9) with BMD. Our data strongly indicate that in patients with primary hyperparathyroidism, bone structure of some skeletal sites, as evaluated by BUA measurement, is compromised to a lesser extent than BMD. In this respect it is interesting to note the lack of significant differences (in terms of mean T-score values) in the comparison of two sites of mostly trabecular composition, that is, the lumbar level (-1.17±1.54) and the femoral Ward's triangle (-0.99±1.25). Our results seem to lend further support to the hypothesis that in primary hyperparathyroidism cancellous bone architecture might be preferentially maintained. Quantitative ultrasound techniques appear to complement, and could possibly substitute for, existing bone densitometry examinations.Submitted in part at the IIIrd European Congress of Endocrinology, Amsterdam, The Netherlands, July 17–22, 1994 and at the 16th Annual Meeting of the American Society for Bone and Mineral Research, Kansas City, MO, USA, September 9–13, 1994.     

Quantitative ultrasound and fracture risk prediction in non-osteoporotic men and women as defined by WHO criteria

Summary

This study sought to determine the association between calcaneal quantitative ultrasound (QUS) and fracture risk in individuals without osteoporosis according to the World Health Organization criteria (i.e., BMD T-score?>??2.5). We found that calcaneal QUS is an independent predictor of fracture risk in women with non-osteoporotic bone mineral density (BMD).

Introduction

More than 50 % of women and 70 % of men who sustain a fragility fracture have BMD above the osteoporotic threshold (T-score?>??2.5). Calcaneal QUS is associated with fracture risk. This study aimed to test the hypothesis that low calcaneal QUS is associated with increased fracture risk in individuals with non-osteoporotic BMD.

Methods

We included 312 women and 390 men aged 62–90 years with BMD T-score?>??2.5 at femoral neck. QUS was measured in broadband ultrasound attenuation (BUA) at the calcaneus using a CUBA sonometer. BMD was measured at the femoral neck (FNBMD) by dual energy X-ray absorptiometry using GE Lunar DPX-L densitometer. The incidences of any fragility fracture were ascertained by X-ray reports during the follow-up period from 1994 to 2011.

Results

Of the 702 participants, 26 % of women (n?=?80/312) and 14 % of men (n?=?53/390) experienced at least one fragility fracture during the follow-up period. In women, after adjusting for covariates, increased risk of any fracture was significantly associated with decreased BUA (HR?=?1.50; 95 % CI, 1.13–1.99). Compared with that of FNBMD, the models with BUA, in women, had greater AUC (0.71, 0.85, 0.71 for any, hip and vertebral fracture, respectively), and yielded a net reclassification improvement of 16.4 % (P?=?0.009) when combined with FNBMD. In men, BUA was not significantly associated with fracture risk before and after adjustment.

Conclusion

These results suggest that calcaneal BUA is an independent predictor of fracture risk in women with non-osteoporotic BMD.     

Can the WHO definition of osteoporosis be applied to multi-site axial transmission quantitative ultrasound?

Osteoporosis is a highly prevalent but preventable disease and, as such, it is important that there are appropriate diagnostic criteria to identify those at risk of low trauma fracture. In 1994 the World Health Organization (WHO) introduced definitions of osteoporosis and osteopenia using T-scores, which identified 30% of all Caucasian post-menopausal women as having osteoporosis. However, the use of the WHO T-score thresholds of –2.5 for osteoporosis and –1.0 for osteopenia may be inappropriate at skeletal sites other than the spine, hip and forearm or when other modalities, such as quantitative ultrasound (QUS) are used. The aim of this study was to evaluate the age-dependence of T-scores for speed of sound (SOS) measurements at the radius, tibia, phalanx and metatarsal by use of the Sunlight Omnisense, to evaluate the prevalence of osteoporosis and osteopenia at these sites by use of the WHO criteria, and calculate appropriate equivalent T-score thresholds. The study population consisted of 278 healthy pre-menopausal women, 194 healthy post-menopausal women and 115 women with atraumatic vertebral fractures. All women had SOS measurements at the radius, tibia, phalanx and metatarsal and bone mineral density (BMD) measurements at the lumbar spine and hip. A group of healthy pre-menopausal women aged 20–40 years from the pre-menopausal group were used to estimate the population mean and SD for each of the SOS and BMD measurement sites. Healthy post-menopausal women were classified into normal, osteopenic or osteoporotic, based upon the standard WHO definition of osteoporosis and expressed as a percentage. We investigated the age-related decline in T-scores from 20–79 by stratifying the healthy subjects into 10-year age groups and calculating the mean T-score for each of these groups. Finally, we estimated appropriate T-score thresholds, using five different approaches. The prevalence of osteoporosis in the post-menopausal women aged 50 years and over ranged from 1.4 to 12.7% for SOS and 1.3 to 5.2% for BMD. The age-related decline in T-scores ranged from –0.92 to –1.80 for SOS measurements in the 60 to 69-year age group and –0.60 to –1.19 for BMD measurements in the same age group. The WHO definition was not suitable for use with SOS measurements, and revised T-score thresholds for the diagnosis of osteoporosis of –2.6, –3.0, –3.0 and –2.2 and for osteopenia of –1.4, –1.6, –2.3, and –1.4, for the radius, tibia, phalanx and metatarsal, respectively, were recommended.     

Correlation of ultrasound velocity in the tibial cortex,calcaneal ultrasonography,and bone mineral densitometry of the spine and femur

We compared the attributes of tibial cortex speed of sound (SOS) measurements with the SOS and broadband ultrasound attenuation (BUA) of the calcaneus, and bone mineral densities of the lumbar spine and femoral neck in a patient crossover study. The three instruments used in the crossover study were the LUNAR DPX and Achilles^TM, and a newly introduced device for measuring tibial cortical SOS, the SoundScan^TM 2000. Ultrasound precision determinations on the two instruments were performed with the same group of 10 volunteers, and the bone densitometry precision was derived from 22 patients who were assessed twice in a single visit, with repositioning between spine and hip scans. There were 220 female patients in the clinical study, 28 of whom had thoracic spine fractures, and all had measurements with the three instruments. Of the three instruments, the best precision, or lowest coefficient of variation and standardized coefficient of variation, was obtained with the SoundScan^TM 2000; 0.20% and 1.39%, respectively. The tibial SOS correlated more poorly with the lumbar spine and femoral neck bone mineral densities (BMDs) than the calcaneal parameters in 220 patients. Tibial SOS measurements could not distinguish the group with spinal fracture from an age-matched control group to aP<0.05 level, whereas the lumbar spine BMD and calcaneal BUA and stiffness showed a significant difference. We conclude that the SoundScan^TM 2000 system measures propagation of sound in the tibial cortex with great precision, but its role in clinical practice is moot. Yet to be established by a long-term prospective study is its efficacy in predicting fracture risk and how well it reflects bone change in response to treatment of osteoporosis.     

Separate and Combined Value of Bone Mass and Gait Speed Measurements in Screening for Hip Fracture Risk: Results from the EPIDOS Study

Based on data from the EPIDOS prospective study, we have shown that femoral bone mineral density (BMD), calcaneal ultrasound measurements and fall-related factors are significant predictors of the risk of hip fracture. The goal of the present investigation, in the same cohort of elderly women, was (1) to assess and compare the value of femoral BMD, calcaneal broadband ultrasound attenuation (BUA), gait speed and age for identifying elderly women at high risk of hip fracture and (2) to determine whether combining two or more of these measurements would improve predictive ability over single measures. A total of 5895 elderly women had baseline measurements of femoral neck BMD by dual-energy X-ray absorptiometry, calcaneal BUA and gait speed. During an average of 33 months of follow-up, 170 women suffered a hip fracture. We compared the sensitivity and specificity of single and combined measures for three specific cutoff levels to define high risk, i.e., the median, the top quartile and the top decile of risk. We found that femoral BMD, calcaneal BUA, gait speed and age have approximatively the same discriminant value to identify women at high risk of hip fracture even though certain measures and combinations of measures have a significantly higher sensitivity for certain cutoff levels. The sensitivity of the available screening tools is low, even when they are combined: to obtain a sensitivity of about 80%, approximately 50% of the population must be considered to be at high risk. Received: 13 April 1998 / Accepted: 23 May 1998     

Age-Specific Values and Cutoff Levels for the Diagnosis of Osteoporosis in Quantitative Ultrasound Measurements at the Calcaneus with SAHARA in Healthy Japanese Women: Japanese Population-Based Osteoporosis (JPOS) Study

To establish the reference values of the quantitative ultrasound (QUS) indices in healthy Japanese women and to propose a diagnostic criterion for osteoporosis by means of the QUS indices, 659 healthy women aged 20-79 years recruited from a larger cohort study (JPOS study), were examined for bone mass measurements by QUS at the calcaneus (SAHARA, Hologic Inc., USA) and by dual-energy X-ray absorptiometry at the spine, hip, and distal forearm. We presented 10-year age-specific mean values and T-scores of the QUS indices. The pattern of decrease in the T-score appeared to be linear in the QUS indices and total hip BMD but not in BMD at the spine. The T-score of the QUS of indices of the subjects in their 70s were significantly higher than that of BMD at the spine. The prevalence rates of osteoporosis in the subjects aged 50 and older diagnosed by QUS (8.7% for SOS, 10.7% for BUA) were similar to that diagnosed by total hip BMD (11.5%) and significantly lower than that by the spine BMD (36.1%) when the WHO criteria were applied. We performed receiver-operating characteristic analysis to set a cutoff level of the QUS indices for the diagnosis of osteoporosis to accurately identify the subjects diagnosed by either the spine or total hip BMD. The highest likelihood ratios for SOS and BUA were obtained at the cutoff levels of 1,517.7 m/sec (T-score: -1.58) with the sensitivity of 0.65 and the specificity of 0.65 and 59.5 dB/MHz (T-score: -1.52) with 0.66 and 0.69, respectively. The diagnostic accuracy of QUS indices for osteoporosis was not superior to that of age. However, the QUS indices showed a significant contribution to forming the diagnosis of osteoporosis independently of age and body size in multivariate diagnostic models developed by the logistic regression analysis. Therefore, the cutoff values presented in this study may be used as a tentative criterion until the cutoff levels for the QUS indices are set according to the fracture risk.     

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.     

Radial and Metacarpal Bone Mineral Density and Calcaneal Quantitative Ultrasound Bone Mass in Normal Japanese Women

The purpose of this study was to examine the effect of lifetime physical activity of farmers on skeletal status. Seventy-one healthy, postmenopausal women (mean age 52.3 ± 5.9 years, range 42–61 years) who worked professionally on farms were compared with 78 matched controls (mean age 51.8 ± 5.5 years, range 42–61 years). Broadband ultrasound attenuation (BUA) and speed of sound (SOS) at the os calcis were measured using an ultrasound transmission imaging system. Bone mineral density (BMD) of the lumbar spine and femoral neck were measured by dual-energy X-ray absorptiometry (DXA). Differences in BUA, SOS, and BMD between farmers and controls were expressed relative to standard deviation (SD) of the farmers. Farmers had significantly higher density values than controls (difference = 1.3 SD in the spine and 1.5 SD in the femoral neck, P < 0.0001 for both comparisons). Ultrasound values were significantly higher in the farmers compared with the controls in calcaneus (difference = 1.1 SD for BUA and 0.7 SD for SOS, P < 0.0001 for both comparisons). The difference of spine BMD, femoral neck BMD, BUA, and SOS between farmers and controls, as judged by comparison of the slopes of the regression lines, was unchanged with age and years since menopause. These results suggest that lifetime physical activity has a positive effect on bone status of postmenopausal farmers. Received: 19 March 1998 / Accepted: 7 August 1998     

Quantitative ultrasound parameters as well as bone mineral density are better predictors of trochanteric than cervical hip fractures in elderly women. Results from the EPIDOS study

RATIONALE: Hip fractures can be separated into cervical and trochanteric fractures. Trochanteric fractures have been associated with up to twice the short-term mortality of cervical fractures in the elderly. There is also evidence suggesting that the mechanisms are different. Evidence from the literature remains limited on the predictive power of bone mineral density (BMD) and quantitative ultrasounds (QUS) for both types of hip fractures. METHODS: 5703 elderly women aged 75 years or more, who were recruited from the voting lists in the EPIDOS study, and had baseline calcaneal ultrasounds (QUS) and DXA measurements at the hip and the whole body, were analyzed in this paper. Among those, 192 hip fractures occurred during an average follow-up of 4 years, 108 cervical and 84 trochanteric fractures. RESULTS: Femoral neck, trochanteric and whole body BMD were able to predict trochanteric hip fracture (RR's and 95% CI were, respectively, 3.2 (2.4-4.2); 4.8 (3.5-6.6); and 2.8 (2.2-3.6)) more accurately than cervical fractures (respectively, 2.1 (1.7-2.7); 2.3 (1.8-3.0); 1.2 (1.0-1.6)). All ultrasound parameters, SOS, BUA, and stiffness index (SI) were significant predictors of trochanteric (RR's respectively 3.0 (2.2-4.1), 2.5(2.0-3.1), and 3.5(2.6-4.7)) but not cervical fractures. After adjustment for femoral neck or trochanteric BMD ultrasound parameters were still significant predictors of trochanteric fracture, and stiffness tended to be a better predictor of trochanteric fractures than either BUA or SOS with a relative risk of 2.25 (1.6-3.1). CONCLUSIONS: A significant decrease of all bone measurements, BMD and QUS, was highly predictive of trochanteric fractures, whereas a decrease of femoral neck and trochanteric BMD were only associated with a slight increase in cervical fracture risk and a low total body BMD or QUS parameters were not significant predictors of cervical fractures. In women who sustained a hip fracture, the decrease of BMD and QUS values increases the risk of trochanteric fracture as compared to cervical fracture. Trochanteric fractures were mostly a consequence of a generalized low BMD and QUS, whereas other parameters might be involved in cervical fractures.     

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.     

Unique and common genetic effects between bone mineral density and calcaneal quantitative ultrasound measures: the Fels Longitudinal Study

Introduction Areal bone mineral density (BMD) and calcaneal quantitative ultrasound (QUS) measures are correlated, and both traits predict osteoporotic fracture risk independently. However, few studies have examined whether common genetic effects (i.e., pleiotropy) exist between these traits in extended families. In this study, we estimated the additive genetic correlation and random environmental correlation between BMD measured at various skeletal sites and calcaneal QUS measures. Methods Our sample included 537 adults (251 men and 286 women) from 110 families participating in the Fels Longitudinal Study. Total hip, femoral neck, lumbar spine, and total body BMD were measured using dual energy X-ray absorptiometry. Three measures of calcaneal structure – broadband ultrasound attenuation (BUA), speed of sound (SOS), and quantitative ultrasound index (QUI) – were collected from the non-dominant heel using the Sahara sonometer. Applying a variance components-based maximum likelihood method, we estimated the heritability of each trait and estimated the genetic and environmental correlations between the different BMD and QUS measures. Results Heritability estimates were significant for all measures of BMD and QUS ranging from 0.55 to 0.78. Significant non-zero genetic correlations were found between the different BMD and QUS measures. All genetic correlations were also significantly different from 1. Genetic correlations between total hip BMD and each of the QUS measures were 0.63 with BUA, 0.50 with SOS, and 0.56 with QUI. For femoral neck BMD, genetic correlations were similar to those between total hip BMD and QUS measures. Genetic correlations between BMD of the lumbar spine and QUS measures ranged from 0.34 to 0.38, and those between total body BMD and QUS measures, from 0.51 to 0.54. In contrast, all random environmental correlations were not significantly different from zero. Conclusion This study demonstrates that BMD and calcaneal QUS measures among healthy men and women are significantly heritable and are, in part, jointly influenced by a common set of underlying genes. Additionally, this study also provides evidence for a unique set of genes that independently influences each individual trait.