Effectiveness of a two-step population-based osteoporosis screening program using FRAX: the randomized Risk-stratified Osteoporosis Strategy Evaluation (ROSE) study.

The Risk-stratified Osteoporosis Strategy Evaluation (ROSE) study investigated the effectiveness of a two-step screening program for osteoporosis in women. We found no overall reduction in fractures from systematic screening compared to the current case-finding strategy. The group of moderate- to high-risk women, who accepted the invitation to DXA, seemed to benefit from the program. INTRODUCTION: The purpose of the ROSE study was to investigate the effectiveness of a two-step population-based osteoporosis screening program using the Fracture Risk Assessment Tool (FRAX) derived from a self-administered questionnaire to select women for DXA scan. After the scanning, standard osteoporosis management according to Danish national guidelines was followed. METHODS: Participants were randomized to either screening or control group, and randomization was stratified according to age and area of residence. Inclusion took place from February 2010 to November 2011. Participants received a self-administered questionnaire, and women in the screening group with a FRAX score ≥ 15% (major osteoporotic fractures) were invited to a DXA scan. Primary outcome was incident clinical fractures. Intention-to-treat analysis and two per-protocol analyses were performed. RESULTS: A total of 3416 fractures were observed during a median follow-up of 5 years. No significant differences were found in the intention-to-treat analyses with 34,229 women included aged 65-80 years. The per-protocol analyses showed a risk reduction in the group that underwent DXA scanning compared to women in the control group with a FRAX ≥ 15%, in regard to major osteoporotic fractures, hip fractures, and all fractures. The risk reduction was most pronounced for hip fractures (adjusted SHR 0.741, p = 0.007). CONCLUSIONS: Compared to an office-based case-finding strategy, the two-step systematic screening strategy had no overall effect on fracture incidence. The two-step strategy seemed, however, to be beneficial in the group of women who were identified by FRAX as moderate- or high-risk patients and complied with DXA.

Non-participation in systematic screening for osteoporosis-the ROSE trial.

Population-based screening for osteoporosis is still controversial and has not been implemented. Non-participation in systematic screening was evaluated in 34,229 women age 65-81 years. Although participation rate was high, non-participation was associated with comorbidity, aging other risk factors for fractures, and markers of low social status, e.g., low income, pension, and living alone. A range of strategies is needed to increase participation, including development of targeted information and further research to better understand the barriers and enablers in screening for osteoporosis. INTRODUCTION: Participation is crucial to the success of a screening program. The objective of this study was to analyze non-participation in Risk-stratified Osteoporosis Strategy Evaluation, a two-step population-based screening program for osteoporosis. METHODS: Thirty-four thousand two hundred twenty-nine women aged 65 to 81 years were randomly selected from the background population and randomized to either a screening group (intervention) or a control group. All women received a self-administered questionnaire designed to allow calculation of future risk of fracture based on FRAX. In the intervention group, women with an estimated high risk of future fracture were invited to DXA scanning. Information on individual socioeconomic status and comorbidity was obtained from national registers. RESULTS: A completed questionnaire was returned by 20,905 (61%) women. Non-completion was associated with older age, living alone, lower education, lower income, and higher comorbidity. In the intervention group, ticking "not interested in DXA" in the questionnaire was associated with older age, living alone, and low self-perceived fracture risk. Women with previous fracture or history of parental hip fracture were more likely to accept screening by DXA. Dropping out when offered DXA, was associated with older age, current smoking, higher alcohol consumption, and physical impairment. CONCLUSIONS: Barriers to population-based screening for osteoporosis appear to be both psychosocial and physical in nature. Women who decline are older, have lower self-perceived fracture risk, and more often live alone compared to women who accept the program. Dropping out after primary acceptance is associated not only with aging and physical impairment but also with current smoking and alcohol consumption. Measures to increase program participation could include targeted information and reducing physical barriers for attending screening procedures.

Characterization of a new ultrasound device designed for measuring cortical porosity at the human tibia: A phantom study.

Quantitative ultrasound (QUS) measurements of trabecular bone are a useful tool for the assessment of osteoporotic fracture risk. However, cortical bone properties (e.g. porosity) have an impact on bone strength as well and thus current research is focused on QUS assessment of cortical bone properties. Simulation studies of ultrasound propagation through cortical bone indicate that anisotropy, calculated from the ratio of the velocities in axial and tangential directions, is correlated with porosity. However, this relationship is affected by error sources, specifically bone surface curvature and variability of probe positioning. With the aim of in vivo estimation of cortical porosity a new ultrasound device was developed, which sequentially measures velocities in 3 different directions (axial=0° and ±37.5°) using the axial transmission method. Measurements on planar porosity phantoms (0-25%) were performed to confirm the results of the afore mentioned simulation studies. Additionally, measurements on cylindrical phantoms without pores (min. radius=34mm for strongest curvature) were performed to estimate the influence of surface curvature on velocity measurements (the tibia bone surface is fairly flat but may show surface curvature in some patients). The velocities in the axial and ±37.5° directions were used to calculate an anisotropy index. The velocities measured on the porosity phantoms showed a decrease by -6.3±0.2m/s and -10.1±0.2m/s per percent increase in porosity in axial and ±37.5° directions, respectively. Surface curvature had an effect on the velocities measured in ±37.5° directions which could be minimized by a correction algorithm resulting in an error of 5m/s. The anisotropy index could be used to estimate porosity with an accuracy error of 1.5%. These results indicate that an estimation of porosity using velocity measurements in different directions might be feasible, even in bones with curved surface. These results obtained on phantom material indicate that the approach tested may be suited for porosity measurements on human tibia bone.

Effects of parathyroid hormone on cortical porosity, non-enzymatic glycation and bone tissue mechanics in rats with type 2 diabetes mellitus.

Type 2 diabetes mellitus increases skeletal fragility; however, the contributing mechanisms and the efficacy of bone-forming agents are unclear. We studied diabetes and parathyroid hormone (PTH) treatment effects on cortical porosity (Ct.Po), non-enzymatic glycation (NEG) and bone mechanics in Zucker diabetic fatty (ZDF) rats. Eleven-week old ZDF diabetic (DB) and non-diabetic (ND) rats were given 75µg/kg PTH (1-84) or vehicle 5days per week over 12weeks. The right femora and L4 vertebrae were excised, micro-CT scanned, and tested in 3-point bending and uniaxial compression, respectively. NEG of the samples was determined using fluorescence. Diabetes increased Ct.Po (vertebra (vert): +40.6%, femur (fem): +15.5% vs. ND group, p<0.05) but had no effect on NEG. PTH therapy reduced vertebral NEG in the ND animals only (-73% vs untreated group, p<0.05), and increased femoral NEG in the DB vs. ND groups (+63%, p<0.05). PTH therapy had no effect on Ct.Po. Diabetes negatively affected bone tissue mechanics where reductions in vertebral maximum strain (-22%) and toughness (-42%) were observed in the DB vs. ND group (p<0.05). PTH improved maximum strain in the vertebra of the ND animals (+21%, p<0.05) but did not have an effect in the DB group. PTH increased femoral maximum strain (+21%) and toughness (+28%) in ND and decreased femoral maximum stress (-13%) and toughness (-27%) in the DB animals (treated vs. untreated, p<0.05). Ct.Po correlated negatively with maximum stress (fem: R=-0.35, p<0.05, vert: R=-0.57, p<0.01), maximum strain (fem: R=-0.35, p<0.05, vert: R=-0.43, p<0.05) and toughness (fem: R=-0.34, p<0.05, vert: R=-0.55, p<0.01), and NEG correlated negatively with toughness at the femur (R=-0.34, p<0.05) and maximum strain at the vertebra (R=-0.49, p<0.05). Diabetes increased cortical porosity and reduced bone mechanics, which were not improved with PTH treatment. PTH therapy alone may worsen diabetic bone mechanics through formation of new bone with high AGEs cross-linking. Optimal treatment regimens must address both improvements of bone mass and glycemic control in order to successfully reduce diabetic bone fragility. This article is part of a Special Issue entitled "Bone and diabetes".

Self-perceived facture risk: factors underlying women's perception of risk for osteoporotic fractures: the Risk-Stratified Osteoporosis Strategy Evaluation study (ROSE).

SUMMARY: This Danish cross-sectional study (n=20,905) showed that women aged 65-81 years generally underestimated fracture risk compared to absolute risk estimated by the FRAX® algorithm. Significant association was found between risk factors (e.g., previous fracture, parental hip fracture, and self-rated heath) and self-perceived fracture risk. Although women recognized the importance of some fracture risk factors, a number of significant risk factors appeared to be less well known. INTRODUCTION: The aim of this study is to investigate women's self-perceived fracture risk and potential factors associated with this and to compare self-perceived risk with absolute fracture risk estimated by FRAX® in women aged 65-80 years. METHODS: Data from 20,905 questionnaires from the ROSE study were analyzed. The questionnaire included 25 items on osteoporosis, risk factors for fractures, and self-perceived risk of fractures and enabled calculation of absolute fracture risk by FRAX®. Data were analyzed using bivariate tests and regression models. RESULTS: Women generally underestimated their fracture risk compared to absolute risk estimated by FRAX®. Women with risk factors for facture estimated their fracture risk significantly higher than their peers. No correlation between self-perceived risk and absolute risk was found. The ordered logistic regression model showed a significant association between high self-perceived fracture risk and previous fragility fracture, parental hip fracture, falls, self-rated heath, conditions related to secondary osteoporosis, and inability to do housework. CONCLUSIONS: These women aged 65-81 years underestimated their risk of fracture. However, they did seem to have an understanding of the importance of some risk factors such as previous fractures, parental hip fracture and falls. Risk communication is a key element in fracture prevention and should have greater focus on less well-known risk factors. Furthermore, it is important to acknowledge that risk perception is not based solely on potential risk factors but is also affected by experiences from everyday life to personal history.

The preliminary evaluation of a 1 MHz ultrasound probe for measuring the elastic anisotropy of human cortical bone.

Our objective is to evaluate an ultrasound probe for measurements of velocity and anisotropy in human cortical bone (tibia). The anisotropy of cortical bone is a known and mechanically relevant property in the context of osteoporotic fracture risk. Current in vivo quantitative ultrasound devices measuring the velocity of ultrasound in long bones can only be applied in the axial direction. For anisotropy measurements a second direction for velocity measurements preferably perpendicular to the axial direction is necessary. We developed a new ultrasound probe which permits axial transmission measurements with a simultaneous second perpendicular direction (tangential). Anisotropy measurements were performed on isotropic and anisotropic phantoms and two excised human female tibiae (age 63 and 82). Anisotropy ratios (AI; ratio of squared ultrasound velocities in the two directions) were for the isotropic phantom 1.06 ± 0.01 and for the anisotropic phantom 1.14 ± 0.03 (mean ± standard deviation). AI was 1.83 ± 0.29 in the tibia from the older donor and 1.37 ± 0.18 in the tibia from the younger donor. The AIs were in the expected range and differed significantly (p<0.05, t-test) between the tibiae. Measured sound velocities were reproducible (mean standard deviation of short time precision of both channels for phantom measurements 31 m/s) and in agreement with reported velocities of the phantom material. Our results document the feasibility of anisotropy measurements at long bones using a single probe. Further improvements in the design of the probe and tests in vivo are warranted. If this approach can be evaluated in vivo an additional tool for assessing the bone status is available for clinical use.

A European multicenter comparison of quantitative ultrasound measurement variables: the OPUS study.

UNLABELLED: Quantitative ultrasound (QUS) measurement variables vary between European countries in a different way to hip bone mineral density. Standardization of data can be achieved through statistical approaches to reduce any between-center differences in QUS measurement variables. However, further validation of this method is required before it can be widely applied. INTRODUCTION: European between-center differences in hip bone mineral density (BMD) have been shown to exist; however, little is known about the geographical heterogeneity of QUS measurement variables. We aimed to examine the differences in QUS variables between three different European countries. METHODS: Five calcaneal and phalangeal QUS devices in Sheffield, Aberdeen (UK), Kiel and Berlin (Germany), and three devices in Paris (France) were used to measure QUS variables in younger (n = 463, 20-39 years old) and older (n = 2,399, 55-79 years old) women participating in the European multicenter Osteoporosis and Ultrasound (OPUS) study. Broadband ultrasound attenuation, speed of sound, stiffness index, amplitude-dependent speed of sound, bone transmission time, and ultrasonic bone profiler index data were collected. Between-center differences were examined using ANOVA followed by post hoc Fisher's least significant difference tests, and ANCOVA with linear contrasts. p < 0.05 indicated statistical significance. RESULTS: Between-center differences in nonstandardized QUS measurement variables existed for younger (p = 0.0023 to p < 0.0001) and older women (p < 0.001). Anthropometric characteristics exerted a significant influence on nonstandardized data (p = 0.045 to p < 0.001). However, following statistical standardization, based on height and weight or based on measurements made in young people, geographical heterogeneity in QUS measurement variables was no longer apparent. CONCLUSIONS: QUS measurement variables vary between European countries in a different way to those for hip BMD. Standardization of data can be achieved through statistical approaches to reduce any between-center differences in QUS measurement variables. However, further validation of this method is required before it can be widely applied.

International variation in proximal femur bone mineral density.

UNLABELLED: We observed higher proximal femur bone mineral density (BMD) in European women compared to average values derived from US Caucasian women in the National Health and Nutrition Examination Survey (NHANES) study. Across European centres, Parisian women had lower proximal femur BMD compared to women from Kiel or Sheffield. INTRODUCTION: Proximal femur BMD of US adults (NHANES III) may not accurately reflect that of European women. We examined the heterogeneity of BMD across European and US Caucasian women and across different European populations. METHODS: Proximal femur BMD was measured in women ages 20-39 years (n=258) and 55-79 years (n=1,426) from three European centres. Cross-calibrated BMD for total hip, femoral neck, trochanter and intertrochanter were examined. International variation in BMD was assessed by comparing means and SDs in the European data with those from the US NHANES III study. European populations were stratified into 5-year age bands to establish individual centre reference intervals. Between-centre differences were assessed using ANOVA and post hoc Fisher's least significant difference tests. RESULTS: European women had higher BMD than US women: The differences were 7.1% to 14.2% (p<0.001) and 0% to 3.9% (p<0.05) in the older and younger women, respectively. Standard deviations for BMD at the different sites were comparable to those for US women. Among older, but not younger European women, proximal femur BMD was significantly lower in French women (Paris) than in women from Germany (Kiel) or the UK (Sheffield) (difference=5.0% to 9.6%, p<0.05). CONCLUSIONS: International variation in hip BMD does exist, with international and between-centre differences being less evident at the femoral neck.

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

SUMMARY: A 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. INTRODUCTION: Dual 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. METHODS: Using 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. RESULTS: Hip 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 R (2) up to 0.72 and a residual error of about one half of a T-score in BMD. CONCLUSIONS: QUS 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.

Influence of density, elasticity, and structure on ultrasound transmission through trabecular bone cylinders.

The aim of this in vitro study is to evaluate the potentiality of quantitative ultrasound (QUS) to separate information on density, elasticity, and structure on specimens of trabecular bone. Fifteen cylinders of spongy bone extracted from equine vertebrae were progressively demineralized and subjected to QUS, micro computed tomography (muCT), Dual energy X-ray absorptiometry (DXA) at various mineralization levels. Eventually all cylinders underwent a compression test to calculate the Young's modulus. Correlation analysis shows that speed of sound (SOS) is strictly associated to bone mineral density (BMD), Young's modulus, and all muCT parameters except for degree of anisotropy (DA). Fast wave amplitude (FWA) is directly correlated with bone surface and total volume ratio (BS/TV) and trabecular separation (Tb Sp), and inversely correlated with trabecular number (Tb N). Because muCT parameters were strictly correlated to BMD and Young's modulus data, partial correlation analysis was performed between SOS, FWA, and structural and elastic data in order to eliminate the effect of density. SOS was significantly correlated to bone volume and total volume ratio (BV/TV), BS/TV, and Young's modulus, and FWA was significantly correlated to Tb Sp only. These results show that SOS is strongly influenced by volumetric mineral bone density and elastic modulus of the specimen, and FWA is mainly affected by trabecular separation independently on density. Therefore, SOS and FWA are able to provide different and complementary information, at least on trabecular bone samples.

Glucocorticosteroid-induced osteoporosis in adult primiparous Göttingen miniature pigs: effects on bone mineral and mineral metabolism.

Information on the pathophysiology of glucocorticoid-induced osteoporosis (GIO) is limited, since its clinical picture often reflects a combined effect of glucocorticoids (GC) and the treated systemic disease (i.e., inflammation and immobility). In 50 healthy adult (30-mo-old) primiparous Göttingen minipigs, we studied the short-term (8 mo, n = 30) and long-term (15 mo, n = 10) effect of GC on bone and mineral metabolism longitudinally and cross-sectionally compared with a control group (n = 10). All animals on GC treatment received prednisolone orally at a dose of 1.0 mg x kg body wt(-1) x day(-1) for 8 wk and thereafter at 0.5 mg/kg body wt(-1) x day(-1). In the short term, GC reduced bone mineral density (BMD) at the lumbar spine by -47.5 +/- 5.1 mg/cm(3) from baseline (P < 0.001), which was greater (P < 0.05) than the loss [not significant (NS)] in the control group of -11.8 +/- 12.6 mg/cm(3). Calcium absorption decreased from baseline by -2,488 +/- 688 mg/7 days (P < 0.001) compared with -1,380 +/- 1,297 mg/7 days (NS) in the control group. Plasma bone alkaline phosphatase (BAP) decreased from baseline by -17.8 +/- 2.2 U/l (P < 0.000), which was significantly different (P < 0.05) from the value of the control group of -1.43 +/- 4.8 U/l. In the long term, the loss of BMD became more pronounced and bone mineral content (BMC), trabecular thickness, mechanical stability, calcium absorption, 25-hydroxyvitamin D(3), 1,25-dihydroxyvitamin D(3), and parathyroid hormone tended to be lower compared with the control group. There was a negative association between the cumulative dose of GC and BMD, which was associated with impaired osteoblastogenesis. In conclusion, the main outcomes after GC treatment are comparable to symptoms of GC-induced osteoporosis in human subjects. Thus the adult Göttingen miniature pig appears to be a valuable animal model for GC-induced osteoporosis.

Ibandronate treatment reverses glucocorticoid-induced loss of bone mineral density and strength in minipigs.

The Göttingen minipig is one of the few large animal models that show glucocorticoid (GC)-induced bone loss. We investigated whether GC-induced loss of bone mineral density (BMD) and bone strength in minipigs can be recovered by treatment with the bisphosphonate ibandronate (IBN). 40 primiparous sows were allocated to 4 groups when they were 30 months old: GC treatment for 8 months (GC8), for 15 months (GC15), GC treatment for 15 months plus IBN treatment for months 8-15 (GC&IBN), and a control group without GC treatment. Prednisolone was given at a daily oral dose of 1 mg/kg body weight for 8 weeks and thereafter 0.5 mg/kg body weight. IBN was administered intramuscularly and intermittently with an integral dose of 2.0 mg/kg body weight. BMD of the lumbar spine (L1-3) was assessed in vivo by Quantitative Computed Tomography (QCT) at months 0, 8, and 15. Blood and urine samples were obtained every 2-3 months. After sacrificing the animals lumbar vertebrae L4 were tested mechanically (Young's modulus and ultimate stress). Histomorphometry was performed on L2 and mineral content determined in ashed specimens of T12 and L4. In the GC&IBN group, the GC associated losses in BMD of -10.5%+/-1.9% (mean+/-standard error of the mean, p<0.001) during the first 8 months were more than recovered during the following 7 months of IBN treatment (+14.8%+/-1.2%, p<0.0001). This increase was significantly larger (p<0.0001) than the insignificant +2.1%+/-1.2% change in group GC15. At month 15, the difference between groups GC&IBN and GC15 was 22% (p<0.01) for BMD, 48% (p<0.05) for Young's modulus, and 31% (p<0.14) for ultimate stress; bone-specific alkaline phosphatase showed trends to lower values (p<0.2) while deoxypyridinoline was comparable. This minipig study demonstrates that GC-induced impairment of bone strength can be effectively and consistently treated by IBN. GC&IBN associated alterations in BMD and bone turnover markers can be monitored in vivo using QCT of the spine and by biochemical analyses, reflecting the changes in bone strength.

A method for the estimation of femoral bone mineral density from variables of ultrasound transmission through the human femur.

Quantitative ultrasound (QUS) measurements at peripheral sites can be used to estimate osteoporotic fracture risk. However, measurements at these sites are less suitable to predict bone mineral density (BMD) or fracture risk at the central skeleton. We investigated whether direct QUS measurements at the femur would allow to estimate dual X-ray absorptiometry (DXA) BMD of the total proximal femur with errors comparable to established DXA accuracy errors. Two independent sets of femora were measured in Kiel (6 f, 4 m, age: 55-90) and Paris (19 f, 20 m age: 45-95) using different benchtop systems in the two laboratories. The femora were scanned in transverse transmission mode using focused US transducers of 500 kHz center frequency. The QUS values were averaged over a region similar to the total hip region of dual X-ray absorptiometry (DXA) measurements. BMD was measured using DXA. SOS and BMD correlated significantly (p<0.0001) in both data sets (R2=0.81-0.93). Correlations between BUA and BMD were also significant at p<0.001, but correlation coefficients were lower (R2=0.61-0.75). Residual errors for the estimation of BMD were 8%-10% for SOS as predictor, and 14%-16% for BUA as predictor. The residual error of 8 to 10% for the estimation of BMD from SOS is comparable to variabilities among different DXA femur subregions and accuracy errors of femoral DXA measurements caused by the impact of soft tissue. It is substantially smaller than the errors of 13% for the estimation of total femur BMD from spine BMD, 14% for the estimation of total femur BMD from calcaneus SOS or 16% for the estimation of ash weight from DXA. The results of the study show that SOS is able to predict total BMD with adequate accuracy. If femoral BMD could be obtained in vivo with comparable accuracy, femoral QUS would be suited for the assessment of bone status at one of the main osteoporotic fracture sites.

[Parametric biomedical imaging--what defines the quality of quantitative radiological approaches?]. / Parametrische biomedizinische Bildgebung--was macht die Qualität quantitativer radiologischer Verfahren aus?

Quantitative parametric imaging approaches provide new perspectives for radiological imaging. These include quantitative 2D, 3D, and 4D visualization options along with the parametric depiction of biological tissue properties and tissue function. This allows the interpretation of radiological data from a biochemical, biomechanical, or physiological perspective. Quantification permits the detection of small changes that are not yet visually apparent, thus allowing application in early disease diagnosis and monitoring therapy with enhanced sensitivity. This review outlines the potential of quantitative parametric imaging methods and demonstrates this on the basis of a few exemplary applications. One field of particular interest, the use of these methods for investigational new drug application studies, is presented. Assessment criteria for judging the quality of quantitative imaging approaches are discussed in the context of the potential and the limitations of these methods. While quantitative parametric imaging methods do not replace but rather supplement established visual interpretation methods in radiology, they do open up new perspectives for diagnosis and prognosis and in particular for monitoring disease progression and therapy.

[Quantitative ultrasound]. / Quantitativer Ultraschall.

Methods of quantitative ultrasound (QUS) can be used to obtain knowledge about bone fragility. Comprehensive study results exist showing the power of QUS for the estimation of osteoporotic fracture risk. Nevertheless, the variety of technologies, devices, and variables as well as different degrees of validation of the single devices have to be taken into account. Using methods to simulate ultrasound propagation, the complex interaction between ultrasound and bone could be understood and the propagation could be visualized. Preceding widespread clinical use, it has to be clarified if patients with low QUS values will profit from therapy, as it has been shown for DXA. Moreover, the introduction of quality assurance measures is essential. The user should know the limitations of the methods and be able to interpret the results correctly. Applied in an adequate manner QUS methods could then, due to lower costs and absence of ionizing radiation, become important players in osteoporosis management.

Numerical simulation of the dependence of quantitative ultrasonic parameters on trabecular bone microarchitecture and elastic constants.

Finite-difference numerical simulation of ultrasound propagation in complex media such as cancellous bone represents a fertile alternative to analytical approaches because it can manage the complex 3D bone structure by coupling the numerical computation with 3D numerical models of bone microarchitecture obtained from high-resolution imaging modalities. The objective of this work was to assess in silico the sensitivity of ultrasound parameters to controlled changes of microarchitecture and variation of elastic constants. The simulation software uses a finite-difference approach based on the Virieux numerical scheme. An incident plane wave was propagated through a volume of bone of approximately 5 x 5 x 8 mm(3). The volumes were reconstructed from high-resolution micro-computed tomography data. An iterative numerical scenario of "virtual osteoporosis" was implemented using a dedicated image processing algorithm in order to modify the initial 3D microstructures. Numerical computations of wave propagation were performed at each step of the process. The sensitivity to bone material properties was also tested by changing the elastic constants of bone tissue. Our results suggest that ultrasonic variables (slope of the frequency-dependent attenuation coefficient and speed of sound) are mostly influenced by bone volume fraction. However, material properties and structure also appear to play a role. The impact of modifications of the stiffness coefficients remained lower than the variability caused by structural variations. This study emphasizes the potential of numerical computations tools coupled to realistic 3D structures to elucidate the physical mechanisms of interaction between ultrasound and bone structure and to assess the sensitivity of ultrasound variables to different bone properties.

Optimal prediction of bone mineral density with ultrasonic measurements in excised human femur.

Bone mineral density (BMD) measured with dual energy X-ray absorptiometry (DXA) techniques is the current gold standard for osteoporotic fracture risk prediction. Quantitative ultrasound (QUS) techniques in transmission measurements are, however, increasingly recognized as an alternative approach. It is feasible to select different QUS methods, one type being optimized to assess microarchitectural properties of bone structure and another to assess BMD. Broadband ultrasonic attenuation (BUA) and ultrasonic velocity (UV) measured on the proximal human femur have been shown to be both significantly correlated with BMD. However, a great diversity of algorithms has been reported to measure the time-of-flight used to derive UV values. The purpose of this study was to determine which procedure results in the optimal BMD prediction at the proximal femur from ultrasound measurements. Thirty-eight excised human femurs were measured in transmission with a pair of focused 0.5-MHz central frequency transducers. Two-dimensional scans were performed and radiofrequency (RF) signals were recorded digitally at each scan position. BUA was estimated and eight different signal processing techniques were performed to estimate UV. For each signal-processing technique UV was compared to BMD. We show that the best prediction of BMD was obtained with signal-processing techniques taking into account only the first part of the transmitted signal (r2BMD-SOS = 0.86). Moreover, we show that a linear multiple regression using both BUA and speed of sound (SOS) and applied to site-matched regions of interest improved the accuracy of BMD predictions (r2BMD-SOS/BUA = 0.95). Our results demonstrate that selecting specific signal-processing methods for QUS variables allows optimal assessment of BMD. Correlation is sufficiently high that this specific QUS method can be considered as a good surrogate of BMD.

In vitro speed of sound measurement at intact human femur specimens.

Quantitative ultrasound has been recognized as a useful tool for fracture risk prediction. Current measurement techniques are limited to peripheral skeletal sites. Our objective was to demonstrate the in vitro feasibility of ultrasonic velocity measurements on human proximal femur and to investigate the relationship between velocity and bone mineral density (BMD). Sound velocity images were computed from 2-D scans performed on 38 excised human femurs in transmission at 0.5 MHz. Different regions-of-interest were investigated. Dual x-ray absorptiometry scans have been achieved for BMD measurements in site-matched regions. Our study demonstrates the feasibility of ultrasonic velocity measurements at the hip with reasonable precision (coefficient of variation of 0.3%). The best prediction of BMD was reached in the intertrochanter region (r(2) = 0.91, p < 10(-4)), with a residual error of 0.06 g/cm(2) (10%). Because BMD measured at the femur is the best predictor of hip fracture risk, the highly significant correlation and small residual error found in this study suggest that speed of sound measurement at the femur might be a good candidate for hip fracture risk prediction.

[Quantitative ultrasound for the diagnosis of osteoporosis]. / Quantitativer Ultraschall zur Osteoporosediagnostik.

Quantitative ultrasound (QUS) methods are promising tools for the assessment of the bone status in osteoporosis. The techniques are based on changes in speed and amplitude of a broadband ultrasound signal propagating through the bone. However, ultrasound propagation through the anisotropic bone is complex and cannot be described in a simple way. The devices are easy to use, inexpensive, portable, do not use ionizing radiation, and therefore have advantages compared to conventional densitometry. This review discusses the technical basics, current research, clinical applications, points of weakness, and future prospects of QUS. For better understanding ultrasound propagation through bone is visualized with a simulation software.

German pediatric reference data for quantitative transverse transmission ultrasound of finger phalanges.

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.