Reinhard Barkmann

Association of Five Quantitative Ultrasound Devices and Bone Densitometry With Osteoporotic Vertebral Fractures in a Population-Based Sample: The OPUS Study

We compared the performance of five QUS devices with DXA in a population‐based sample of 2837 women. All QUS approaches discriminated women with and without osteoporotic vertebral fractures. QUS of the calcaneus performed as well as central DXA.

A New Method for Quantitative Ultrasound Measurements at Multiple Skeletal Sites: First Results of Precision and Fracture Discrimination

We investigated a new multisite quantitative ultrasound device that measures the acoustic velocity in axial transmission mode along the cortex. Using a prototype of the Omnisense (Sunlight Ultrasound Technologies, Rehovot, Israel), we tested the performance of this instrument at four sites of the skeleton: radius, ulna, metacarpal, and phalanx. Intraobserver (interobserver) precision errors ranged from 0.2% to 0.3% (0.3% to 0.7%) for triplicate measurements with repositioning. Fracture discrimination was tested by comparing a group of 34 women who had previously suffered a fracture of the hip, spine, ankle, or forearm to a group of 28 healthy women who had not suffered a fracture. Age-adjusted standardized odds ratios ranged from 1.6 to 4.5. Except for the ulna the sites showed a significant fracture discrimination (p < 0.01). The areas under the receiver operating curves (ROC) curves were from 0.88 to 0.89 for radius, metacarpal, and phalanx. A combination of the results from the three sites showed a significant increase of the ROC area to 0.95 (p < 0. 05). Our results show promising performance of this new device. The ability to measure a large variety of sites and the potential to combine these measurements are promising with regard to optimizing fracture risk assessment.

Does combining the results from multiple bone sites measured by a new quantitative ultrasound device improve discrimination of hip fracture

There is a growing interest in the use of quantitative ultrasound (QUS) measurements as an alternative to current radiation‐based bone densitometry techniques for the noninvasive assessment of fracture risk. While most of the commercialized ultrasound devices measure only single predefined peripheral skeletal sites, the Omnisense prototype (Sunlight Ltd., Israel) can be used on multiple bones, including the spinous processes. In this study, we examined the ability of speed of sound measured at the calcaneus, distal third and ultradistal radius, proximal third phalanx, metacarpal, capitate, patella, and the posterior process of the thoracic spine to differentiate subjects with hip fractures from normal controls. Seventy‐nine postmenopausal Caucasian Israeli women who had sustained an atraumatic fracture of the proximal femur within the last 6 months were recruited from the local population (mean age 80 ± 8.9 years). As controls, 295 postmenopausal Caucasian Israeli women without osteoporotic fractures were also included (mean age 70 ± 8.7 years). Discrimination of hip fractures with QUS at all ultrasound sites was highly statistically significant (p < 0.01) (odds ratios [ORs] = 1.4–3.0; area under the ROC curve [AUC] 77–92%), except for the hand metacarpal. Distal radius and calcaneus measurements (ORs = 2.4 and 3.0) were the best discriminators of hip fracture patients from controls. Using a forward selective linear regression model, the discriminator values of combined assessment at two sites were investigated. There was moderate improvement in diagnostic value, but the best combination was the calcaneus with the distal radius, which improved the AUC by 3% and raised both the sensitivity and specificity to 94%. These data demonstrate the encouraging potential of improving discrimination of hip fracture by using multiple‐site ultrasonic measurements.

A Meta‐Analysis of Trabecular Bone Score in Fracture Risk Prediction and Its Relationship to FRAX

Trabecular bone score (TBS) is a gray‐level textural index of bone microarchitecture derived from lumbar spine dual‐energy X‐ray absorptiometry (DXA) images. TBS is a bone mineral density (BMD)‐independent predictor of fracture risk. The objective of this meta‐analysis was to determine whether TBS predicted fracture risk independently of FRAX probability and to examine their combined performance by adjusting the FRAX probability for TBS. We utilized individual‐level data from 17,809 men and women in 14 prospective population‐based cohorts. Baseline evaluation included TBS and the FRAX risk variables, and outcomes during follow‐up (mean 6.7 years) comprised major osteoporotic fractures. The association between TBS, FRAX probabilities, and the risk of fracture was examined using an extension of the Poisson regression model in each cohort and for each sex and expressed as the gradient of risk (GR; hazard ratio per 1 SD change in risk variable in direction of increased risk). FRAX probabilities were adjusted for TBS using an adjustment factor derived from an independent cohort (the Manitoba Bone Density Cohort). Overall, the GR of TBS for major osteoporotic fracture was 1.44 (95% confidence interval [CI] 1.35–1.53) when adjusted for age and time since baseline and was similar in men and women (p > 0.10). When additionally adjusted for FRAX 10‐year probability of major osteoporotic fracture, TBS remained a significant, independent predictor for fracture (GR = 1.32, 95% CI 1.24–1.41). The adjustment of FRAX probability for TBS resulted in a small increase in the GR (1.76, 95% CI 1.65–1.87 versus 1.70, 95% CI 1.60–1.81). A smaller change in GR for hip fracture was observed (FRAX hip fracture probability GR 2.25 vs. 2.22). TBS is a significant predictor of fracture risk independently of FRAX. The findings support the use of TBS as a potential adjustment for FRAX probability, though the impact of the adjustment remains to be determined in the context of clinical assessment guidelines.

Assessment of the Geometry of Human Finger Phalanges Using Quantitative Ultrasound In Vivo

Abstract: Quantitative Ultrasound (QUS) methods have been shown to be useful in the assessment of bone status. Nevertheless, ultrasound transmission depends on a variety of skeletal parameters, and a detailed understanding of ultrasound propagation through bone is important for the accurate interpretation of QUS results. In this study we wanted to elucidate the pathways of an ultrasound wave through finger phalanges and determine correlations between geometric and QUS parameters. Phalanges of a subject group were measured using QUS and magnetic resonance imaging (MRI). MRI was used for the derivation of the geometric parameters. Similar assessments were performed on cylindrical tubes and with a simulation program. New parameters related to speed of sound (SOS) and amplitude of the wave (A2P) were calculated. Strong correlations between QUS parameters and morphologic cross-sectional areas were observed in vivo and in phantoms. Similar correlations could be found in the calculations using the simulation software. Cross-sectional cortical area, medullary canal area and relative cortical area could be calculated from the QUS parameters (subjects: R2= 0.71 for cortical area, R2 = 0.45 for medullary canal area and R2= 0.61 for relative cortical area; phantoms: R2= 0.98 for cortical area, R2= 0.78 for medullary canal area and R2= 0.77 for relative cortical area). In vivo, phantom and simulation results consistently showed that SOS was correlated with cortical area but not with medullary canal area while the opposite was found for A2P. Pathways of the ultrasound wave through solid cortical bone and the medullary canal could be identified and the propagation of the wave could be depicted. These results help to interpret QUS findings and provide information that may be helpful in improving the performance of QUS.

German Pediatric Reference Data for Quantitative Transverse Transmission Ultrasound of Finger Phalanges

Abstract: Quantitative ultrasound (QUS) of the finger phalanges is a useful tool in the assessment of disease- or age-related deterioration of bone. For studying the impact of juvenile diseases or growth disorders affecting the skeleton, a reference database for QUS parameters is needed. The aim of this study was to establish a calibrated reference database of parameters of transverse ultrasound transmission through juvenile finger phalanges. A total of 1328 children (650 females, 678 males; ages 3–17 years) were measured in Heidelberg and Kiel in order to establish a German reference database. Highly significant gender-specific correlations (p<0.0001) were found between the QUS parameters amplitude-dependent speed of sound (AD-SoS) and bone transmission time (BTT) versus age, body height and body mass index (BMI). For AD-SoS the correlation coefficients were R2= 0.64 against age in males and R2= 0.73 in females, R2= 0.60 against body height in males and R2= 0.68 in females, and R2= 0.19 against BMI in males and R2= 0.23 in females. For BTT the correlation coefficients were R2= 0.74 against age in males and R2= 0.79 in females, R2= 0.75 against body height in males and R2= 0.77 in females, and R2= 0.32 against BMI in males and R2= 0.35 in females. Age and height were the strongest determinants of QUS results. Gender-specific differences were observed in AD-SoS (significant for ages 11–14 years and for 150–170 cm body height) and in BTT (significant for ages 7 and 11–17 years and for 160–170 cm body height). Tables of QUS parameters versus age and height can serve as a basis for the evaluation of the impact of skeletal diseases or growth disorders on phalangeal QUS. Depending on the type of disease or growth disorder, measurement results can be compared with age- or height- specific reference data. In this way a simple and radiation-free assessment of juvenile skeletal disorders using quantitative ultrasound might be possible in the future.

Assessing Bone Status Beyond BMD: Evaluation of Bone Geometry and Porosity by Quantitative Ultrasound of Human Finger Phalanges

In an in vitro study, we found significant associations between QUS variables and properties and geometrical parameters of the compact bone of human finger phalanges. QUS variables were not only related to BMD but also to other skeletal properties, which explained 70% of the variability of speed of sound.

Comparison of different screening tools (FRAX®, OST, ORAI, OSIRIS, SCORE and age alone) to identify women with increased risk of fracture. A population-based prospective study

PURPOSE To compare the power of FRAX® without bone mineral density (BMD) and simpler screening tools (OST, ORAI, OSIRIS, SCORE and age alone) in predicting fractures. METHODS This study was a prospective, population-based study performed in Denmark comprising 3614 women aged 40-90 years, who returned a questionnaire concerning items on risk factors for osteoporosis. Fracture risk was calculated using the different screening tools (FRAX®, OST, ORAI, OSIRIS and SCORE) for each woman. The women were followed using the Danish National Register registering new major osteoporotic fractures during 3 years, counting only the first fracture per person. Area under the receiver operating characteristic curve (ROC) and statistics and Harrells index were calculated. Agreement between the tools was calculated by kappa statistics. RESULTS A total of 4% of the women experienced a new major osteoporotic fracture during the follow-up period. There were no differences in the area under the curve (AUC) values between FRAX® and the simpler tools; AUC values between 0.703 and 0.722 (p = 0.86). Also, Harrells C values were very similar between the tools. Agreement between the tools was modest. CONCLUSION During 3 years follow-up FRAX® did not perform better in the fracture risk prediction compared with simpler tools such as OST, ORAI, OSIRIS, SCORE or age alone in a screening scenario where BMD was not measured. These findings suggest that simpler models based on fewer risk factors, which would be easier to use in clinical practice by the GP or the patient herself, could just as well as FRAX® be used to identify women with increased risk of fracture. SUMMARY Comparison of FRAX® and simpler screening tools (OST, ORAI, OSIRIS, SCORE) in predicting fractures indicate that FRAX® did not perform better in fracture risk prediction compared with the simpler tools or even age alone in a screening scenario without bone mineral density assessment.

Femur ultrasound (FemUS)—first clinical results on hip fracture discrimination and estimation of femoral BMD

SummaryA quantitative ultrasound (QUS) device for measurements at the proximal femur was developed and tested in vivo (Femur Ultrasound Scanner, FemUS). Hip fracture discrimination was as good as for DXA, and a high correlation with hip BMD was achieved. Our results show promise for enhanced QUS-based assessment of osteoporosis.IntroductionDual X-ray absorptiometry (DXA) at the femur is the best predictor of hip fractures, better than DXA measurements at other sites. Calcaneal quantitative ultrasound (QUS) can be used to estimate the general osteoporotic fracture risk, but no femoral QUS measurement has been introduced yet. We developed a QUS scanner for measurements at the femur (Femur Ultrasound Scanner, FemUS) and tested its in vivo performance.MethodsUsing the FemUS device, we obtained femoral QUS and DXA on 32 women with recent hip fractures and 30 controls. Fracture discrimination and the correlation with femur bone mineral density (BMD) were assessed.ResultsHip fracture discrimination using the FemUS device was at least as good as with hip DXA and calcaneal QUS. Significant correlations with total hip bone mineral density were found with a correlation coefficient R2 up to 0.72 and a residual error of about one half of a T-score in BMD.ConclusionsQUS measurements at the proximal femur are feasible and show a good performance for hip fracture discrimination. Given the promising results, this laboratory prototype should be reengineered to a clinical applicable instrument. Our results show promise for further enhancement of QUS-based assessment of osteoporosis.

A device for in vivo measurements of quantitative ultrasound variables at the human proximal femur

Quantitative ultrasound (QUS) at the calcaneus has similar power as a bone mineral density (BMD)- measurement using DXA for the prediction of osteoporotic fracture risk. Ultrasound equipment is less expensive than DXA and free of ionizing radiation. As a mechanical wave, QUS has the potential of measuring different bone properties than dual X-ray absorptiometry (DXA,) which depends on X-ray attenuation and might be developed into a tool of comprehensive assessment of bone strength. However, site- specific DXA at the proximal femur shows best performance in the prediction of hip fractures. To combine the potential of QUS with measurements directly at the femur, we developed a device for in vivo QUS measurements at this site. Methods comprise ultrasound transmission through the bone, reflection from the bone surface, and backscat- ter from the inner trabecular structure. The complete area of the proximal femur can be scanned except at the femoral head, which interferes with the ilium. To avoid edge artifacts, a subregion of the proximal femur in the trochanteric region was selected as measurement region. First, in vivo measurements demonstrate a good signal to noise ratio and proper depiction of the proximal femur on an attenuation image. Our results demonstrate the feasibility of in vivo measurements. Further improvements can be expected by refinement of the scanning technique and data evaluation method to enhance the potential of the new method for the estimation of bone strength.