Broadband ultrasound attenuation signals depend on trabecular orientation: An in vitro study

Quantitative ultrasound (QUS) techniques have recently been introduced as alternative methods free of ionizing radiation for non-invasive assessment of skeletal status in osteoporosis. We carried out an in vitro study on bone specimens to investigate whether broadband ultrasound attenuation (BUA) signals are associated with bone structure, specifically with the orientation of the trabeculae, and whether this association is independent of the association between orientation and bone mineral density (BMD) as measured by dual-energy X-ray absorptiometry (DXA). BUA and BMD of 10 cubical specimens of purely trabecular bovine bone were examined along the three principal axes. The relative orientation of the trabeculae with respect to the direction of the ultrasound beam was evaluated on high-resolution conventional radiographs employing a semiquantitative ALIGNMENT score ranging from –2 (for perpendicular) to +2 (parallel). BUA variability was 27.6 dB/MHz, reflecting both inter-specimen (18.2 dB/MHz) and intra-specimen (19.4 dB/MHz) variability at comparable levels and to a much lesser extent reproducibility errors (1 dB/MHz). BUA was 44%–54% larger along the axis of the compressive trabeculae as compared with the two perpendicular axes. BMD and ALIGNMENT showed independent significant associations with BUA. A change in ALIGNMENT from perpendicular to parallel corresponded to a difference in BUA of 36.1 dB/MHz. The substantial level of intra-specimen variability suggests that BUA reflects anisotropical characteristics of trabecular bone. The association of BUA and ALIGNMENT indicates that BUA signals depend on trabecular orientation. This association is independent of BMD, indicating that BUA has considerable potential for non-invasive assessment of bone structure and strength, free of ionizing radiation, and for complementing existing bone densitometry examinations.     

Relationship between bone quantitative ultrasound and mortality: a prospective study

Summary

In a cohort of 5,201 women [72.3?±?5.3 years] from 58 primary care centers in Spain, followed for three years, no relationship between heel QUS parameters and overall mortality was found. However, a significant relationship between a low speed of sound (SOS) and vascular mortality was observed.

Introduction

An inverse relationship between mortality and bone mineral density measured by dual-energy absorption densitometry or quantitative bone ultrasound (QUS) has been described. The aim of the present study was to test this relationship in the ECOSAP cohort, a 3-year prospective study designed to assess the ability of heel QUS and clinical risk factors to predict non-vertebral fracture risk in women over 64.

Methods

A cohort of 5,201 women [72.3?±?5.3 years] was studied. QUS was assessed with the Sahara® bone sonometer. Women attended follow-up visits every 6 months. Physicians recorded if the patient died and cause of death. Hazard rates (HR) of all-cause and vascular mortality per one standard deviation reduction in QUS parameters were determined.

Results

One hundred (1.9%) women died during a median of 36.1 months follow-up, for a total of 14,999 patient-years, 42 because of vascular events (both cardiovascular and cerebrovascular). After adjusting for age, none of the QUS variables showed statistically significant differences between the patients who died and the survivors. In the final multivariate model, adjusted for age, current thyroxine and hypoglycaemic drug use, chronic obstructive pulmonary disease and decreased visual acuity, SOS was marginally non-significant: (HR: 1.19; 0.97–1.45). However, each 1 SD reduction in SOS was associated with a 39% increase in vascular mortality (HR: 1.39; 1.15–1.66).

Conclusions

In our cohort, SOS was related with vascular mortality, but not overall mortality.     

Cortical ultrasound velocity as an indicator of bone status

Normative population data are reported here for velocity of ultrasound in tibial cortical bone in a population-based sample of both men and women (n=371). The cortical measurement is highly precise with reproducibility of the order of 0.5%. As with heel and patellar trabecular velocity, tibial cortical velocity declines with age from the fourth through the ninth decades. The rate is 1.7 m/s per year in men and 4.1 m/s per year in women. Tibial cortical velocity values correlate with patellar velocity and with forearm mineral, with correlation coefficients ranging from + 0.46 to +0.54 in women and +0.27 to +0.43 in men (P<0.002 for all). Tibial velocity averaged 77–104 m/s lower (2–3%: equal to about 1 SD of the young adult normal distribution) in individuals with a history of low-energy appendicular fractures (P<0.05), and the difference remained significant after adjusting for age. However, there were no perceptible differences in tibial velocity for those with and without vertebral fractures. Odds ratios derived from logistic regression showed an approximate twofold increase in likelihood of low-energy appendicular fracture for every standard deviation decrement in velocity. Comparison of tibial velocity with patellar velocity and forearm density in the same individuals revealed tibial velocity to be more strongly associated with appendicular fractures than patellar velocity for women and about the same for men, and less strongly associated than patellar velocity for vertebral fractures. We conclude that tibial cortical velocity provides useful information about bone status in populations at risk for osteoporosis, and seems particularly well suited for assessing appendicular fracture risk.     

The association of patellar ultrasound transmissions and forearm densitometry with vertebral fracture,number and severity: The saunders county bone quality study

Ultrasonic measures of bone have been available for clinical research purposes for nearly 10 years, yet there still seems to be a need to compare ultrasound with the accepted gold standard of densitometry. Recently there have been published reports showing that ultrasound measures are associated with both appendicular and hip fracture, in particular after adjustment for densitometry measures. We present here a comparison between speed of sound through the patella and forearm bone densitometry, using their association with prevalent vertebral fractures in a population-based study of women and men. The prospective phase of the Saunders Bone Quality Study includes 1401 women and men who had baseline spine radiographs, patellar ultrasound, and forearm densitometry measurements. Multivariate forward logistic regression was used to determine the age-adjusted odds of vertebral fracture, the number of fractures, and the severity of these fractures, when patellar ultrasound and each of four forearm densitometry measures were entered into the model. Age is the most important factor associated with vertebral fractures, their number, and severity for women, while age is not significantly related to vertebral fractures for men. Of the bone status measures, patellar ultrasound entered the logistic regression models more consistently than any other measure except ulnar bone mineral density for women. The ultrasound measure entered every model for men. We conclude that patellar ultrasound velocity is more consistently associated with the odds of vertebral fractures than radius bone mineral content.     

Preliminary evaluation of a new ultrasound bone densitometer

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

跟骨超声骨质测量与双能量X线吸收骨密度测量的比较

我们试图通过对跟骨超声骨质测量仪与双能量Ｘ线吸收骨密度测量仪的临床对比，来评价跟骨超声骨质测量仪的敏感性。本文对５６名健康女性同时接受了超声骨质测量仪和双能量Ｘ线吸收骨密度仪的检测。３７例（年龄２６～７６岁）进行了跟骨超声和腰椎骨密度测量，１９例（年龄２６～７０岁）进行了跟骨超声和股骨颈骨密度测量。结果用ＳＹＳＴＡＴ统计软件包进行处理。结果表明：随着年龄的增加，腰椎、股骨颈骨密度及跟骨强度（Ｓｔｉｆｆｎｅｓｓ）均显著下降（Ｐ＜０．０５），两种仪器的阳性检出率无明显差异（Ｐ＜０．０５）。但腰椎和股骨颈ＢＭＤ与跟骨强度（Ｓｔｉｆｆｎｅｓｓ）的相关性适中ｒ＝０．４６５～０．５１３左右。通过逐步多元回归分析显示超声强度（Ｓｔｉｆｆｎｅｓｓ）与ＢＭＤ无关。这表明超声波测量仪主要测量骨的结构变化，而骨密度测量仪则是测量骨量的变化。两种方法相辅相承，共同测量，将更好地预测骨质疏松性骨折的发生。同时超声波具有无放射线损害、价格低廉及良好的敏感性，将越来越受到临床重视。     

Broadband ultrasound attentuation compared with dual-energy X-ray absorptiometry in screening for postmenopausal low bone density

Broadband ultrasound attenuation (BUA) was investigated as an inexpensive, simple and radiation-free method of screening for low perimenopausal bone density. A total of 587 women (50–54 years), invited for screening had bone mineral density (BMD) measured at the femoral neck and the lumbar spine by dual-energy X-ray absorptiometry (DXA). At the same visit the BUA of the calcaneus was measured. The correlation between BUA and BMD was approximately 0.4 compared with 0.67 between femoral neck and spinal BMD. Receiver operating characteristic (ROC) curve analysis demonstrated BUA to have the same ability for discriminating between low BMD at either the femoral neck or lumbar spine. BUA with a cut-off for normality at the median (BUA=80) had a sensitivity of 68% and specificity of 67% for low bone density identified by a BMD less than the 25th centile at the femoral neck or lumbar spine. The correlation between BUA and BMD was insufficient to allow identification of the same groups as having low bone density.     

Prediction of absolute risk of non-spinal fractures using clinical risk factors and heel quantitative ultrasound

SUMMARY: The relationship between osteoporosis risk factors, bone quantitative ultrasound (QUS) and non-spinal fracture risk was estimated in a cohort of 5,201 postmenopausal women from Spain who were prospectively evaluated during three years. Several clinical risk factors and low heel QUS values were independently associated with non-spinal fracture risk. INTRODUCTION: Low-trauma, non-spinal fractures are a growing source of morbidity and mortality in the elderly. The aim of the present study was to examine the association of heel quantitative ultrasound (QUS) and a series of osteoporosis and fracture risk factors, with incident low energy non-spinal fractures in a population of elderly women, and to incorporate them into fracture prediction models. METHODS: 5,201 women aged 65 or older were enrolled in a three-year cohort study. Participants completed an osteoporosis and fracture risk factors questionnaire. QUS was measured at the heel with a gel-coupled device. Cox-proportional hazard analyses were performed to evaluate the association with the first incident low-trauma non-spinal fracture. RESULTS: Three hundred and eleven women (6.0%) sustained a total of 363 low-trauma fractures, including 133 forearm/wrist, 54 hip, 50 humerus, 37 leg and 17 pelvic fractures. For every standard deviation decrease in the quantitative ultrasound index, the adjusted hazard ratios (95% CI) for any non-vertebral, hip, forearm/wrist, and humerus fractures were 1.31 (1.15-1.49), 1.40 (1.01-1.95), 1.50 (1.19-1.89) and 1.35 (0.97-1.87), respectively. Similar results were observed with other QUS variables. The best predictive models indicated that age, a history of falls, a previous low-trauma fracture, a family history of fracture, a calcium intake from dairy products of less than 250 mg/day, and lower values of QUS parameters were independently associated with the risk of non-spinal fractures. CONCLUSIONS: Both clinical risk factors and QUS are independent predictors of risk of fragility non-spinal fractures. A prediction algorithm using these variables was developed to estimate the absolute risk of non-spinal fractures in elderly women in Spain.     

Skin thickness does not reflect bone mineral density in postmenopausal women

Skin and bone both contain primarily type I collagen in connective tissue matrices and are assumed to be related due to this common organic constituent. The purpose of this study was to investigate whether skin thickness measurements by ultrasound (US) could be used for screening for low bone mass. In 94 healthy, white, non-smoking women, 1–3 years postmenopause, the thickness of the skin of the left upper arm and forearm was measured by ultrasound (US). These measurements were compared with values of bone mineral density (BMD) as measured by quantitative computed tomography (QCT) of the lumbar spine and quantitative video micro-densitometry (QMD) of the hand. The correlation found between US skin thickness measurements and BMD results was of low magnitude and not significant. It is concluded that US measurements of skin thickness cannot be used to screen early postmenopausal women for low bone mass.     

Quality assurance for bone densitometry research studies: Concept and impact

A concept for quality assurance (QA) in bone densitometry has been developed for clinical multicenter studies. Major elements provided by a coordinating center comprise (1) consulting services and certification of participating centers in the start-up phase of the study, (2) review of scan data acquired on QA standards for cross-calibration and longitudinal assessment of scanner stability, (3) review of selected patient data as well as of problem cases during the study, and (4) comprehensive review and correction of patient results based on QA data after conclusion of the study. Limitations of phantom-based QA data should be acknowledged. Typical problems encountered during research studies and guidelines for solutions are presented. Successful implementation of QA measures may yield substantial enhancement of statistical power. Depending on the study design and the variability of response within patient groups, improvement in precision due to QA measures may reduce the smallest detectable difference between subject groups or, alternatively, sample size by a few to more than 50%, and thus may contribute to a substantial reduction in study cost. Formulae for calculation of the magnitude of these effects are presented. To maximize the net benefit, QA efforts have to be limited to levels that assure reliability of the data at acceptable QA cost. While QA programs at individual clinical sites or for local practitioners may not need to be as extensive as for multicenter clinical trials, awareness of the potential problems and implementation of basic QA measures will help in obtaining high-quality bone densitometry results.