The risk-stratified osteoporosis strategy evaluation study (ROSE): a randomized prospective population-based study. Design and baseline characteristics.

The risk-stratified osteoporosis strategy evaluation study (ROSE) is a randomized prospective population-based study investigating the effectiveness of a two-step screening program for osteoporosis in women. This paper reports the study design and baseline characteristics of the study population. 35,000 women aged 65-80 years were selected at random from the population in the Region of Southern Denmark and-before inclusion-randomized to either a screening group or a control group. As first step, a self-administered questionnaire regarding risk factors for osteoporosis based on FRAX(®) was issued to both groups. As second step, subjects in the screening group with a 10-year probability of major osteoporotic fractures ≥15% were offered a DXA scan. Patients diagnosed with osteoporosis from the DXA scan were advised to see their GP and discuss pharmaceutical treatment according to Danish National guidelines. The primary outcome is incident clinical fractures as evaluated through annual follow-up using the Danish National Patient Registry. The secondary outcomes are cost-effectiveness, participation rate, and patient preferences. 20,904 (60%) women participated and included in the baseline analyses (10,411 in screening and 10,949 in control group). The mean age was 71 years. As expected by randomization, the screening and control groups had similar baseline characteristics. Screening for osteoporosis is at present not evidence based according to the WHO screening criteria. The ROSE study is expected to provide knowledge of the effectiveness of a screening strategy that may be implemented in health care systems to prevent fractures.

Ultrasound to assess bone quality.

Bone quality is determined by a variety of compositional, micro- and ultrastructural properties of the mineralized tissue matrix. In contrast to X-ray-based methods, the interaction of acoustic waves with bone tissue carries information about elastic and structural properties of the tissue. Quantitative ultrasound (QUS) methods represent powerful alternatives to ionizing x-ray based assessment of fracture risk. New in vivo applicable methods permit measurements of fracture-relevant properties, [eg, cortical thickness and stiffness at fragile anatomic regions (eg, the distal radius and the proximal femur)]. Experimentally, resonance ultrasound spectroscopy and acoustic microscopy can be used to assess the mesoscale stiffness tensor and elastic maps of the tissue matrix at microscale resolution, respectively. QUS methods, thus, currently represent the most promising approach for noninvasive assessment of components of fragility beyond bone mass and bone microstructure providing prospects for improved assessment of fracture risk.

Dual-Layer Spectral-Computed Tomography Enhances the Separability of Calcium-Based Implant Material from Bone: An Ex Vivo Quantitative Imaging Study.

Local treatment of bone loss with an injection of a resorbable, calcium-based implant material to replace bone has a long history of clinical use. The in vivo discrimination of changes in bone versus implant is challenging with standard computed tomography (CT). However, spectral-CT techniques enable the separation between tissues of similar densities but different chemical compositions. Dual-layer spectral-CT imaging and postprocessing analysis methods were applied to investigate the separability of AGN1 (a triphasic calcium-based implant) and bone after AGN1 injection in n = 10 male cadaveric femurs ex vivo. Using the area under the curve (AUC) from receiver-operating characteristic (ROC) analyses, the separability of AGN1 from bone was assessed for AGN1 (postoperatively) versus compact and versus femoral neck cancellous bone (both preoperatively). CT techniques included conventional Hounsfield (HU) and density-equivalent units (BMD, mg hydroxyapatite [HA]/cm3 ) and spectral-CT measures of effective atomic number (Zeff) and electron density (ED). The samples had a wide range of femoral neck BMD (55.66 to 241.71 mg HA/cm3 ). At the injection site average BMD, HU, Zeff, and ED increased from 69.5 mg HA/cm3 , 109 HU, 104.38 EDW, and 8.30 Zeff in the preoperative to 1233 mg HA/cm3 , 1741 HU, 181.27 EDW, and 13.55 Zeff in the postoperative CT scan, respectively. For compact bone at the femoral shaft the preoperative values were 1124.15 mg HA/cm3 , 1648 HU, 177 EDW, and 13.06 Zeff and were maintained postoperatively. Zeff showed substantially sharper distributions and significantly greater separability compared to ED, BMD, and HU (all p < 0.002, for both regions) with average AUCs for BMD, HU, ED, and Zeff of 0.670, 0.640, 0.645, and 0.753 for AGN1 versus compact and 0.996, 0.995, 0.994, and 0.998 for AGN1 versus femoral neck cancellous sites, respectively. Spectral-CT permits better discrimination of calcium-based implants like AGN1 from bone ex vivo. Our results warrant application of spectral-CT in patients undergoing procedures with similar implants. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Lipid-Iron Nanoparticle with a Cell Stress Release Mechanism Combined with a Local Alternating Magnetic Field Enables Site-Activated Drug Release.

Most available cancer chemotherapies are based on systemically administered small organic molecules, and only a tiny fraction of the drug reaches the disease site. The approach causes significant side effects and limits the outcome of the therapy. Targeted drug delivery provides an alternative to improve the situation. However, due to the poor release characteristics of the delivery systems, limitations remain. This report presents a new approach to address the challenges using two fundamentally different mechanisms to trigger the release from the liposomal carrier. We use an endogenous disease marker, an enzyme, combined with an externally applied magnetic field, to open the delivery system at the correct time only in the disease site. This site-activated release system is a novel two-switch nanomachine that can be regulated by a cell stress-induced enzyme at the cellular level and be remotely controlled using an applied magnetic field. We tested the concept using sphingomyelin-containing liposomes encapsulated with indocyanine green, fluorescent marker, or the anticancer drug cisplatin. We engineered the liposomes by adding paramagnetic beads to act as a receiver of outside magnetic energy. The developed multifunctional liposomes were characterized in vitro in leakage studies and cell internalization studies. The release system was further studied in vivo in imaging and therapy trials using a squamous cell carcinoma tumor in the mouse as a disease model. In vitro studies showed an increased release of loaded material when stress-related enzyme and magnetic field was applied to the carrier liposomes. The theranostic liposomes were found in tumors, and the improved therapeutic effect was shown in the survival studies.

Improved accuracy in the assessment of vertebral cortical thickness by quantitative computed tomography using the Iterative Convolution OptimizatioN (ICON) method.

Vertebral whole bone strength is substantially affected by cortical bone properties. Disease and therapy may affect cancellous and cortical bone differently. Unlike Dual X-ray Absorptiometry (DXA), Quantitative Computed Tomography (QCT) permits selective assessment of cortical and cancellous bone, but image quality limits the accuracy. We present an image processing method specifically adopted to thin cortices that substantially improves accuracy. Ten human vertebrae embedded in epoxy resin were imaged using clinical QCT and High-Resolution QCT (HR-QCT) protocols, both acquired on a clinical whole body CT scanner, whereas high resolution peripheral QCT (HR-pQCT) was used as gold standard. Microstructural variables and BMD were calculated using in-house software StructuralInsight for QCT and HR-QCT and the manufacturer's µCT evaluation software for HR-pQCT. An adjusted measure, a deconvolved cortical thickness (dcCt.Th), corrected for partial volume effects, was derived applying the new Iterative Convolution OptimizatioN (ICON) method. Direct measurements of cortical thickness (Ct.Th) showed substantial overestimation with mean ±â€¯standard deviation of 1.8 ±â€¯0.5 mm for QCT and 1.5 ±â€¯0.3 mm for HR-QCT compared to 0.37 ±â€¯0.07 mm using HR-pQCT. Correlations of both QCT (r2 = 0.05, p > 0.5.) and HR-QCT (r2 = 0.38, p = 0.060) with the gold standard HR-pQCT were not significant. Also QCT-based BMD and BMC as well as HR-QCT-based BMD did not show a significant correlation with the gold standard approach. Only HR-QCT-based BMC showed a modest correlation (r2 = 0.59, p = 0.01) After applying ICON corrections, dcCt.Th resulted in 0.52 ±â€¯0.09 mm for QCT and 0.43 ±â€¯0.07 mm for HR-QCT, both significantly correlated to HR-pQCT (r2 = 0.75, p = 0.0012 and r2 = 0.93, p < 0.0001, respectively). The average overestimation bias of Ct.Th was reduced from (402 ±â€¯157)% to (45 ±â€¯17)% for QCT and from (330 ±â€¯69)% to (19 ±â€¯8)% for HR-QCT. Due to inaccurate segmentation uncorrected QCT-based Ct.Th measures as well as BMD and BMC showed no correlation to HR-pQCT and thus such bias cortical data can be misleading. The application of ICON reduced random overestimation bias to about 50 µm and 20 µm for QCT and HR-QCT, respectively, leading to a recovery of a significant correlation with the reference data of HR-pQCT. This reveals the potential for fairly accurate assessment of cortical thickness, allowing to better characterize cortical mechanical competence. These results warrant testing of the performance in vivo.

Correction: Large cortical bone pores in the tibia are associated with proximal femur strength.

[This corrects the article DOI: 10.1371/journal.pone.0215405.].

Ex vivo cortical porosity and thickness predictions at the tibia using full-spectrum ultrasonic guided-wave analysis.

The estimation of cortical thickness (Ct.Th) and porosity (Ct.Po) at the tibia using axial transmission ultrasound was successfully validated ex vivo against site-matched micro-computed tomography. The assessment of cortical parameters based on full-spectrum guided-wave analysis might improve the prediction of bone fractures in a cost-effective and radiation-free manner. PURPOSE: Cortical thickness (Ct.Th) and porosity (Ct.Po) are key parameters for the identification of patients with fragile bones. The main objective of this ex vivo study was to validate the measurement of Ct.Po and Ct.Th at the tibia using a non-ionizing, low-cost, and portable 500-kHz ultrasound axial transmission system. Additional ultrasonic velocities and site-matched reference parameters were included in the study to broaden the analysis. METHODS: Guided waves were successfully measured ex vivo in 17 human tibiae using a novel 500-kHz bi-directional axial transmission probe. Theoretical dispersion curves of a transverse isotropic free plate model with invariant matrix stiffness were fitted to the experimental dispersion curves in order to estimate Ct.Th and Ct.Po. In addition, the velocities of the first arriving signal (υFAS) and A0 mode (υA0) were measured. Reference Ct.Po, Ct.Th, and vBMD were obtained from site-matched micro-computed tomography. Scanning acoustic microscopy (SAM) provided the acoustic impedance of the axial cortical bone matrix. RESULTS: The best predictions of Ct.Po (R2 = 0.83, RMSE = 2.2%) and Ct.Th (R2 = 0.92, RMSE = 0.2 mm, one outlier excluded) were obtained from the plate model. The second best predictors of Ct.Po and Ct.Th were vBMD (R2 = 0.77, RMSE = 2.6%) and υA0 (R2 = 0.28, RMSE = 0.67 mm), respectively. CONCLUSIONS: Ct.Th and Ct.Po were accurately predicted at the human tibia ex vivo using a transverse isotropic free plate model with invariant matrix stiffness. The model-based predictions were not further enhanced when we accounted for variations in axial tissue stiffness as reflected by the acoustic impedance from SAM.

Large cortical bone pores in the tibia are associated with proximal femur strength.

Alterations of structure and density of cortical bone are associated with fragility fractures and can be assessed in vivo in humans at the tibia. Bone remodeling deficits in aging women have been recently linked to an increase in size of cortical pores. In this ex vivo study, we characterized the cortical microarchitecture of 19 tibiae from human donors (aged 69 to 94 years) to address, whether this can reflect impairments of the mechanical competence of the proximal femur, i.e., a major fracture site in osteoporosis. Scanning acoustic microscopy (12 µm pixel size) provided reference microstructural measurements at the left tibia, while the bone vBMD at this site was obtained using microcomputed tomography (microCT). The areal bone mineral density of both left and right femoral necks (aBMDneck) was measured by dual-energy X-ray absorptiometry (DXA), while homogenized nonlinear finite element models based on high-resolution peripheral quantitative computed tomography provided hip stiffness and strength for one-legged standing and sideways falling loads. Hip strength was associated with aBMDneck (r = 0.74 to 0.78), with tibial cortical thickness (r = 0.81) and with measurements of the tibial cross-sectional geometry (r = 0.48 to 0.73) of the same leg. Tibial vBMD was associated with hip strength only for standing loads (r = 0.59 to 0.65). Cortical porosity (Ct.Po) of the tibia was not associated with any of the femoral parameters. However, the proportion of Ct.Po attributable to large pores (diameter > 100 µm) was associated with hip strength in both standing (r = -0.61) and falling (r = 0.48) conditions. When added to aBMDneck, the prevalence of large pores could explain up to 17% of the femur ultimate force. In conclusion, microstructural characteristics of the tibia reflect hip strength as well as femoral DXA, but it remains to be tested whether such properties can be measured in vivo.

In vivo measurements of ultrasound transmission through the human proximal femur.

Quantitative ultrasound (QUS) measurements can be used to estimate osteoporotic fracture risk. The commonly used variables are the speed of sound (SOS) and the frequency dependent sound attenuation (broadband ultrasound attenuation, [BUA]) of a wave propagating through the bone, preferably the calcaneus. The technology, so far, is less suitable for direct measurement in vivo at the spine or the femur for prediction of bone mineral density (BMD) or fracture risk at the main osteoporotic fracture sites. To improve the clinical performance of QUS, we built a device for direct QUS measurements at the human femur in vivo. In vivo images of ultrasound transmission at one of the main fracture sites, the proximal femur, could be acquired. The estimated precision of SOS measurements of 0.5% achieved at the femur is comparable with the precision of peripheral QUS devices.

BMD-based assessment of local porosity in human femoral cortical bone.

Cortical pores are determinants of the elastic properties and of the ultimate strength of bone tissue. An increase of the overall cortical porosity (Ct.Po) as well as the local coalescence of large pores cause an impairment of the mechanical competence of bone. Therefore, Ct.Po represents a relevant target for identifying patients with high fracture risk. However, given their small size, the in vivo imaging of cortical pores remains challenging. The advent of modern high-resolution peripheral quantitative computed tomography (HR-pQCT) triggered new methods for the clinical assessment of Ct.Po at the peripheral skeleton, either by pore segmentation or by exploiting local bone mineral density (BMD). In this work, we compared BMD-based Ct.Po estimates with high-resolution reference values measured by scanning acoustic microscopy. A calibration rule to estimate local Ct.Po from BMD as assessed by HR-pQCT was derived experimentally. Within areas of interest smaller than 0.5 mm2, our model was able to estimate the local Ct.Po with an error of 3.4%. The incorporation of the BMD inhomogeneity and of one parameter from the BMD distribution of the entire scan volume led to a relative reduction of the estimate error of 30%, if compared to an estimate based on the average BMD. When applied to the assessment of Ct.Po within entire cortical bone cross-sections, the proposed BMD-based method had better accuracy than measurements performed with a conventional threshold-based approach.

Wavelet-based signal processing of in vitro ultrasonic measurements at the proximal femur.

To estimate osteoporotic fracture risk, several techniques for quantitative ultrasound (QUS) measurements at peripheral sites have been developed. As these techniques are limited in the prediction of fracture risk of the central skeleton, such as the hip, we are developing a QUS device for direct measurements at the femur. In doing so, we noticed the necessity to improve the conventional signal processing because it failed in a considerable number of measurements due to multipath transmission. Two sets of excised human femurs (n = 6 + 34) were scanned in transmission mode. Instead of using the conventional methods, the radio-frequency signals were processed with the continuous wavelet transform to detect their time-of-flights for the calculation of speed-of-sound (SOS) in bone. The SOS-values were averaged over a region similar to the total hip region of dual X-ray absorptiometry (DXA) measurements and compared with bone mineral density (BMD) measured with DXA. Testing six standard wavelets, this algorithm failed for only 0% to 6% of scan in test set 1 compared with 29% when using conventional algorithms. For test set 2, it failed for 2% to 12% compared with approximately 40%. SOS and BMD correlated significantly in both test sets (test set 1: r2 = 0.87 to 0.92, p < 0.007; test set 2: r2 = 0.68 to 0.79, p < 0.0001). The correlations are comparable with correlations recently reported. However, the number of evaluable signals could be substantially increased, which improves the perspectives of the in vivo measurements.

Bone-marrow densitometry: Assessment of marrow space of human vertebrae by single energy high resolution-quantitative computed tomography.

PURPOSE: Accurate noninvasive assessment of vertebral bone marrow fat fraction is important for diagnostic assessment of a variety of disorders and therapies known to affect marrow composition. Moreover, it provides a means to correct fat-induced bias of single energy quantitative computed tomography (QCT) based bone mineral density (BMD) measurements. The authors developed new segmentation and calibration methods to obtain quantitative surrogate measures of marrow-fat density in the axial skeleton. METHODS: The authors developed and tested two high resolution-QCT (HR-QCT) based methods which permit segmentation of bone voids in between trabeculae hypothesizing that they are representative of bone marrow space. The methods permit calculation of marrow content in units of mineral equivalent marrow density (MeMD). The first method is based on global thresholding and peeling (GTP) to define a volume of interest away from the transition between trabecular bone and marrow. The second method, morphological filtering (MF), uses spherical elements of different radii (0.1-1.2 mm) and automatically places them in between trabeculae to identify regions with large trabecular interspace, the bone-void space. To determine their performance, data were compared ex vivo to high-resolution peripheral CT (HR-pQCT) images as the gold-standard. The performance of the methods was tested on a set of excised human vertebrae with intact bone marrow tissue representative of an elderly population with low BMD. RESULTS: 86% (GTP) and 87% (MF) of the voxels identified as true marrow space on HR-pQCT images were correctly identified on HR-QCT images and thus these volumes of interest can be considered to be representative of true marrow space. Within this volume, MeMD was estimated with residual errors of 4.8 mg/cm(3) corresponding to accuracy errors in fat fraction on the order of 5% both for GTP and MF methods. CONCLUSIONS: The GTP and MF methods on HR-QCT images permit noninvasive localization and densitometric assessment of marrow fat with residual accuracy errors sufficient to study disorders and therapies known to affect bone marrow composition. Additionally, the methods can be used to correct BMD for fat induced bias. Application and testing in vivo and in longitudinal studies are warranted to determine the clinical performance and value of these methods.

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. © 2015 American Society for Bone and Mineral Research.

Effect of temperature on the longitudinal variability of quantitative ultrasound variables.

It is unclear whether longitudinal change in phantom measurements bears any relation to the long-term in vivo instrument performance of quantitative ultrasound devices. Longitudinal quantitative ultrasound phantom data were obtained by measuring the manufacturer-provided phantom at ambient temperature and two different sets of Leeds phantoms at either ambient temperature or following a phantom temperature-control protocol. Measurements were performed using the Achilles Plus bone densitometer. Changes in longitudinal phantom data were compared to in vivo quantitative ultrasound data obtained from seven healthy, young volunteers. A cosinor model with linear trend and Hotelling's T2-test were used to quantify seasonal rhythms and long-term drift in quantitative ultrasound variables. Temperature effects and marked seasonal rhythms on quantitative ultrasound phantom measurements were evident but were far less apparent in vivo. Longitudinal precision of quantitative ultrasound variables was poorer for the manufacturer-provided phantom than for phantoms that were subjected to a temperature-control protocol or for healthy volunteers. This study has shown that longitudinal precision and longitudinal change differs between in vivo and phantom data. Longitudinal quantitative ultrasound measurements for monitoring change in skeletal status cannot, as yet, be properly controlled.

Quantitative ultrasound measurements at the heel: improvement of short- and mid-term speed of sound precision.

Calcaneal quantitative ultrasound can be used to predict osteoporotic fracture risk, but its ability to monitor therapy is unclear possibly because of its limited precision. We developed a quantitative ultrasound device (foot ultrasound scanner) that measures the speed of sound at the heel with the aim of minimizing common error sources like the position and penetration angle of the ultrasound beam, as well as the soft tissue temperature. To achieve these objectives, we used a receiver array, mechanics to adjust the beam direction and a foot temperature sensor. In a group of 60 volunteers, short-term precision was evaluated for the foot ultrasound scanner and a commercial device (Achilles Insight, GE Medical, Fairfield, CT, USA ). In a subgroup of 20 subjects, mid-term precision (1-mo follow-up) was obtained. Compared with measurement of the speed of sound with the Achilles Insight, measurement with the foot ultrasound scanner reduced precision errors by half (p < 0.05). The study indicates that improvement of the precision of calcaneal quantitative ultrasound measurements is feasible.

Assessing bone status beyond BMD: evaluation of bone geometry and porosity by quantitative ultrasound of human finger phalanges.

UNLABELLED: 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. INTRODUCTION: Transverse transmission quantitative ultrasound (QUS) measurements at the finger phalanges are known to be correlated with BMD and to predict osteoporotic fractures. To determine which other skeletal properties are affected by ultrasound, we investigated the impact of density, geometry, and porosity on QUS variables in vitro. MATERIALS AND METHODS: Ultrasound variables were correlated with density, porosity, and geometrical characteristics of cortical bone. Additionally, we tested which combinations of geometry and bone properties best predicted the ultrasound results observed. Forty-four proximal phalanges from the middle finger were investigated at their distal metaphysis, similar to the typical clinical measurement procedure. Donor age ranged from 52 to 98 years (15 males and 29 females; mean age, 80.9 +/- 9.4 years). QUS variables were measured on the metaphysis of the phalanges using the DBMSonic 1200. Quantitative CT was used for the measurement of BMD, and high-resolution MRI was used for the measurement of porosity and geometrical variables. RESULTS: Speed of sound (SOS) and the clinically used variable AD-SOS correlated significantly with area, relative area, density, and porosity of the compact bone (R2 = 0.28-0.58, p < 0.0001). Signal amplitude correlated significantly only with relative area of the compact bone and area of the medullary canal (R2 = 0.18-0.20, p < 0.01). The combination of cortical area, density, and porosity improved the determination of SOS to R2 = 0.70, with a residual unexplained variability of 54 m/s (3.2%). CONCLUSIONS: These results clarify the impact of skeletal properties on QUS variables. SOS is affected by cortical area, cortical bone density, and cortical porosity, whereas attenuation only depends on geometry of the medulla. AD-SOS, the variable routinely measured in clinical practice, is primarily affected by cortical area. QUS of the finger phalanges is not only related to BMD but also to other skeletal properties.

Association of five quantitative ultrasound devices and bone densitometry with osteoporotic vertebral fractures in a population-based sample: the OPUS Study.

UNLABELLED: 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. INTRODUCTION: Quantitative ultrasound (QUS) methods have found widespread use for the assessment of bone status in osteoporosis, but their optimal use remains to be established. To determine QUS performance for current devices in direct comparison with central DXA, we initiated a large population-based investigation, the Osteoporosis and Ultrasound Study (OPUS). MATERIALS AND METHODS: A total of 463 women 20-39 years of age and 2374 women 55-79 years of age were measured on five different QUS devices along with DXA of the spine and the proximal femur. Their vertebral fracture status was evaluated radiographically. The association of QUS and DXA with vertebral fracture status was evaluated using logistic regression. RESULTS: All QUS approaches tested discriminated women with and without osteoporotic vertebral fractures (20% height reduction), with age-adjusted standardized odds ratios ranging 1.2-1.3 for amplitude-dependent speed of sound (AD-SOS) at the finger phalanges, 1.2-1.4 for broadband ultrasound attenuation (BUA) at the calcaneus, and 1.4-1.5 for speed of sound (SOS) at the calcaneus, 1.4-1.6 for DXA of the total femur, and 1.5-1.6 for DXA at the spine. For more severe fractures (40% height reduction), age-adjusted standardized odds ratios increased to up to 1.9 for DXA of the spine and 2.3 for SOS of the calcaneus. CONCLUSIONS: In conclusion, all five QUS devices tested showed significant age-adjusted differences between subjects with and without vertebral fracture. When selecting the strongest variable, QUS of the calcaneus worked as well as central DXA for identification of women at high risk for prevalent osteoporotic vertebral fractures. QUS-based case-finding strategies would allow halving the number of radiographs in high-risk populations, and this strategy works increasingly well for women with more severe vertebral fractures. It is likely that the good performance of QUS was in part achieved by rigorous quality assurance measures that should also be used in clinical practice.

Women's perspectives and experiences on screening for osteoporosis (Risk-stratified Osteoporosis Strategy Evaluation, ROSE).

UNLABELLED: This study aimed to investigate women's perspectives and experiences with screening for osteoporosis. Focus groups and individual interviews were conducted. Three main themes emerged: knowledge about osteoporosis, psychological aspects of screening, and moral duty. Generally, screening was accepted due to life experiences, self-perceived risk, and the preventive nature of screening. PURPOSE: The risk-stratified osteoporosis strategy evaluation (ROSE) study is a randomized prospective population-based trial investigating the efficacy of a screening program to prevent fractures in women aged 65-80 years. It is recommended by the World Health Organization that a set of criteria are met before a screening program is implemented. This sub-study aims to investigate women's perspectives and experiences with the ROSE screening program in relation to the patient-related criteria recommended by the World Health Organization. METHODS: A qualitative study was carried out involving 31 women by way of 8 focus group interviews and 11 individual interviews. Principles from critical psychology guided the analysis. RESULTS: Women's perspectives and experiences with the screening program were described by three main themes: knowledge about osteoporosis, psychological aspects of screening, and moral duty. The women viewed the program in the context of their everyday life and life trajectories. Age, lifestyle, and knowledge about osteoporosis were important to how women ascribed meaning to the program, how they viewed the possibilities and limitations, and how they rationalized their actions and choices. The women displayed limited knowledge about osteoporosis and its risk factors. However, acceptance was based on prior experience, perceived risk, and evaluation of preventive measures. To be reassured or concerned by screening was described as important issues, as well as the responsibility for health-seeking behaviour. CONCLUSION: In general, the women accepted the screening program. No major ethical reservations or adverse psychological consequences were detected. Only a minority of women declined screening participation due to a low perceived risk of osteoporosis.

Influence of porosity, pore size, and cortical thickness on the propagation of ultrasonic waves guided through the femoral neck cortex: a simulation study.

The femoral neck is a common fracture site in elderly people. The cortical shell is thought to be the major contributor to the mechanical competence of the femoral neck, but its microstructural parameters are not sufficiently accessible under in vivo conditions with current X-ray-based methods. To systematically investigate the influences of pore size, porosity, and thickness of the femoral neck cortex on the propagation of ultrasound, we developed 96 different bone models (combining 6 different pore sizes with 4 different porosities and 4 different thicknesses) and simulated the ultrasound propagation using a finite-difference time-domain algorithm. The simulated single-element emitter and receiver array consisting of 16 elements (8 inferior and 8 superior) were placed at anterior and posterior sides of the bone, respectively (transverse transmission). From each simulation, we analyzed the waveform collected by each of the inferior receiver elements for the one with the shortest time of flight. The first arriving signal of this waveform, which is associated with the wave traveling through the cortical shell, was then evaluated for its three different waveform characteristics (TOF: time point of the first point of inflection of the received signal, Δt: difference between the time point at which the signal first crosses the zero baseline and TOF, and A: amplitude of the first extreme of the first arriving signal). From the analyses of these waveform characteristics, we were able to develop multivariate models to predict pore size, porosity, and cortical thickness, corresponding to the 96 different bone models, with remaining errors in the range of 50 µm for pore size, 1.5% for porosity, and 0.17 mm for cortical thickness.

Modeling of femoral neck cortical bone for the numerical simulation of ultrasound propagation.

Quantitative ultrasound assessment of the cortical compartment of the femur neck (FN) is investigated with the goal of achieving enhanced fracture risk prediction. Measurements at the FN are influenced by bone size, shape and material properties. The work described here was aimed at determining which FN material properties have a significant impact on ultrasound propagation around 0.5 MHz and assessing the relevancy of different models. A methodology for the modeling of ultrasound propagation in the FN, with a focus on the modeling of bone elastic properties based on scanning acoustic microscopy data, is introduced. It is found that the first-arriving ultrasound signal measured in through-transmission at the FN is not influenced by trabecular bone properties or by the heterogeneities of the cortical bone mineralized matrix. In contrast, the signal is sensitive to variations in cortical porosity, which can, to a certain extent, be accounted for by effective properties calculated with the Mori-Tanaka method.