C. C. Glüer

Accurate assessment of precision errors: how to measure the reproducibility of bone densitometry techniques.

Assessment of precision errors in bone mineral densitometry is important for characterization of a techniques ability to detect logitudinal skeletal changes. Short-term and long-term precision errors should be calculated as root-mean-square (RMS) averages of standard deviations of repeated measurements (SD) and standard errors of the estimate of changes in bone density with time (SEE), respectively. Inadequate adjustment for degrees of freedom and use of arithmetic means instead of RMS averages may cause underestimation of true imprecision by up to 41% and 25% (for duplicate measurements), respectively. Calculation of confidence intervals of precision errors based on the number of repeated measurements and the number of subjects assessed serves to characterize limitations of precision error assessments. Provided that precision error are comparable across subjects, examinations with a total of 27 degrees of freedom result in an upper 90% confidence limit of +30% of the mean precision error, a level considered sufficient for characterizing technique imprecision. We recommend three (or four) repeated measurements per individual in a subject group of at least 14 individuals to characterize short-term (or long-term) precision of a technique.

Three Quantitative Ultrasound Parameters Reflect Bone Structure

We investigated whether quantitative ultrasound (QUS) parameters are associated with bone structure. In an in vitro study on 20 cubes of trabecular bone, we measured broadband ultrasound attenuation (BUA) and two newly defined parameters—ultrasound velocity through bone (UVB) and ultrasound attenuation in bone (UAB). Bone mineral density (BMD) was measured by dual X-ray absorptiometry (DXA) and bone structure was assessed by microcomputed tomography (μCT) with approximately 80 μm spatial resolution. We found all three QUS parameters to be significantly associated with bone structure independently of BMD. UVB was largely influenced by trabecular separation, UAB by connectivity, and BUA by a combination of both. For a one standard deviation (SD) increase in UVB, a decrease in trabecular separation of 1.2 SD was required compared with a 1.4 SD increase in BMD for the same effect. A 1.0 SD increase in UAB required a reduction in connectivity of 1.4 SD. Multivariate models of QUS versus BMD combined with bone structure parameters showed squared correlation coefficients of r2=0.70–0.85 for UVB, r2=0.27–0.56 for UAB, and r2=0.30–0.68 for BUA compared with r2=0.18–0.58 for UVB, r2<0.26 for UAB and r2<0.13 for BUA for models including BMD alone. QUS thus reflects bone structure, and a combined analysis of QUS and BMD will allow for a more comprehensive assessment of skeletal status than either method alone.

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.

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.

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, R2u2009=u20090.45 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.

Influence of degenerative joint disease on spinal bone mineral measurements in postmenopausal women.

We assessed the impact of various forms of spinal degenerative joint disease (DJD) on bone mineral density (BMD) measured by quantitative computed tomography (QCT) and dual X-ray absorptiometry (DXA) in a group of postmenopausal women. Lateral (T4-L4) and AP (L1-L4) spinal radiographs were reviewed for fracture and DJD in 209 women (mean age 62.6±6.7). The severity of DJD findings was graded as 0,1, or 2 on the lumbar films, except for vertebral osteophytes which were graded from 0 to 3. Vertebral fractures were defined semiquantitatively as approximately 20% reduction in anterior, middle, or posterior vertebral height. BMD was measured in all subjects by QCT and DXA, including posteroanterior DXA (PA-DXA), lateral DXA (L-DXA) and midlateral DXA (mL-DXA). When BMD was measured by QCT and mL-DXA in the 168 women without fractures, no significant differences were found between women with and those without DJD. However, BMD by PA-DXA was significantly higher in women with DJD changes, particularly when osteophytes were present at the vertebral bodies or facet joints. BMD by L-DXA was less affecied by DJD. For this measurement a significant increase in BMD was only noted in subjects with vertebral osteophytes. Multivariate analysis of variance (MANOVA) showed that BMD by QCT and mL-DXA was not affected by DJD. In contrast, for all women, BMD by PA-and L-DXA was affected more by DJD than by fracture status. Chi-square testing demonstrated no significant relationships between vertebral fractures and any of the DJD changes. We conclude that QCT and mL-DXA are superior to PA-DXA and L-DXA in detecting bone loss in patients with DJD. Thus, for these patients, BMD assessment by QCT or mL-DXA may be advisable.

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.

Cross-calibration of liquid and solid QCT calibration standards: corrections to the UCSF normative data

Quantitative computed tomography (QCT) has been shown to be a precise and sensitive method for evaluating spinal bone mineral density (BMD) and skeletal response to aging and therapy. Precise and accurate determination of BMD using QCT requires a calibration standard to compensate for and reduce the effects of beam-hardening artifacts and scanner drift. The first standards were based on dipotassium hydrogen phosphate (K2HPO4) solutions. Recently, several manufacturers have developed stable solid calibration standards based on calcium hydroxyapatite (CHA) in water-equivalent plastic. Due to differences in attenuating properties of the liquid and solid standards, the calibrated BMD values obtained with each system do not agree. In order to compare and interpret the results obtained on both systems, cross-calibration measurements were performed in phantoms and patients using the University of California San Francisco (UCSF) liquid standard and the Image Analysis (IA) solid standard on the UCSF GE 9800 CT scanner. From the phantom measurements, a highly linear relationship was found between the liquid- and solid-calibrated BMD values. No influence on the cross-calibration due to simulated variations in body size or vertebral fat content was seen, though a significant difference in the cross-calibration was observed between scans acquired at 80 and 140 kVp. From the patient measurements, a linear relationship between the liquid (UCSF) and solid (IA) calibrated values was derived for GE 9800 CT scanners at 80 kVp (IA=[1.15×UCSF]-7.32). The UCSF normative database for women and men obtained with the liquid standard was corrected for use with the solid standard. Proper procedures for cross-calibrating QCT measurements and the appropriate uses of normative data are discussed.

Quality and performance measures in bone densitometry: part 1: errors and diagnosis.

IntroductionBone densitometry is one of the main pillars in the assessment of osteoporosis. The most important modalities are dual x-ray absorptiometry (DXA), quantitative computed tomography (QCT), and quantitative ultrasound (QUS).Materials and methods For each modality a variety of technical solutions and numerous commercial devices are available and widely used for patient measurements. While the field of bone densitometry may be considered mature, new modalities and devices are being introduced. Consequently, there is a constant need to assess and compare the quality of bone densitometry approaches and devices in a rigorous way.ResultsThe International Commission on Radiation Units has commissioned a report on bone densitometry to address some of these issues, in particular to provide clear definitions of quantities and units used and to describe parameters and methods that can be used to compare and standardize densitometric equipment and measurements. One of the core chapters of the report summarizes quality and performance measures in bone densitometry. It is divided into four sections: physical performance measures, diagnosis, fracture risk, and monitoring. Here we publish part 1 of this chapter containing the first two sections: physical performance measures and issues in diagnosing osteoporosis.ConclusionFollowing the international standard (ISO 5725-1), trueness, bias, repeatability, and reproducibility are defined along with terms common to osteoporosis research, such as accuracy and precision. Building on the conceptual definition of osteoporosis, diagnostic criteria are defined and discussed including criteria for reference data. Based on this, clinical performance measures commonly used for the diagnosis of osteoporosis are reviewed and discussed.

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.