Osteoporosis: Prevrhal S

Engelke K, Adams JE, Armbrecht G, Augat P, Bogado CE, Bouxsein ML, Felsenberg D, Ito M, Prevrhal S, Hans DB, Lewiecki EM. · Institute of Medical Physics, University of Erlangen, Germany; Synarc, Hamburg, Germany. <> · J Clin Densitom. · Pubmed #18442757 No free full text.

Abstract: The International Society for Clinical Densitometry (ISCD) has developed Official Positions for the clinical use of dual-energy X-ray absorptiometry (DXA) and non-DXA technologies. While only DXA can be used for diagnostic classification according to criteria established by the World Health Organization, DXA and some other technologies may predict fracture risk and be used to monitor skeletal changes over time. ISCD task forces reviewed the evidence for clinical applications of non-DXA techniques and presented reports with recommendations at the 2007 ISCD Position Development Conference. Here we present the ISCD Official Positions for quantitative computed tomography (QCT) and peripheral QCT (pQCT), with supporting medical evidence, rationale, controversy, and suggestions for further study. QCT is available for bone mineral density measurements at the spine, hip, forearm, and tibia. The ISCD Official Positions presented here focus on QCT of the spine and pQCT of the forearm. Measurements at the hip may have clinical relevance, as this is an important fracture site; however, due to limited medical evidence, definitive advice on its use in clinical practice cannot be provided until more data emerge.

Firoozabadi R, Morshed S, Engelke K, Prevrhal S, Fierlinger A, Miclau T, Genant HK. · Department of Orthopaedic Surgery, University of California San Francisco, San Francisco, California 94143, USA. · J Orthop Trauma. · Pubmed #18753895 No free full text.

Abstract: Fractures of the distal radius are one of the most common injuries presented to orthopaedic surgeons. A variety of treatment options are available for the vast array of fracture patterns. Research that explores bone fragility and fracture healing has led to new treatment modalities. As new products and methods are derived to aid in fracture healing it is essential to develop noninvasive and/or nondestructive techniques to assess structural information about bone. Quantitative assessment of macro-structural characteristics such as geometry, and microstructural features such as relative trabecular volume, trabecular spacing, and connectivity may improve our ability to estimate bone strength. Methods for quantitatively assessing macrostructure include (besides conventional radiographs) dual x-ray absorptiometry (DXA) and computed tomography (CT), particularly volumetric quantitative computed tomography (vQCT). Methods for assessing microstructure of trabecular bone include high resolution computed tomography (hrCT), micro computed tomography (microCT), high resolution magnetic resonance (hrMR), and micro magnetic resonance microMR. Volumetric QCT, hrCT and hrMR are generally applicable in vivo; microCT and microMR are principally applicable in vitro. Clinically, the challenges for bone imaging include balancing the advantages of simple bone densitometry versus the more complex architectural features of bone, or the deeper research requirements versus the broader clinical needs.

Genant HK, Engelke K, Prevrhal S. · University of California, San Francisco, CA, USA. · Rheumatology (Oxford). · Pubmed #18556648 links to  free full text

Abstract: Non-invasive and/or non-destructive techniques can provide structural information about bone, beyond simple bone densitometry. While the latter provides important information about osteoporotic fracture risk, many studies indicate that BMD only partly explains bone strength. Quantitative assessment of macro- and microstructural features may improve our ability to estimate bone strength. Methods for quantitatively assessing macrostructure include (besides conventional radiographs) DXA and CT, particularly volumetric quantitative CT (vQCT). Methods for assessing microstructure of trabecular bone non-invasively and/or non-destructively include high-resolution CT (hrCT), microCT (microCT), high-resolution magnetic resonance (hrMR) and microMR (microMR). vQCT, hrCT and hrMR are generally applicable in vivo; microCT and microMR are principally applicable in vitro. Despite recent progress made with these advanced imaging techniques, certain issues remain. The important balances between spatial resolution and sampling size, or between signal-to-noise and radiation dose or acquisition time, need further consideration, as do the complexity and expense of the methods vs their availability and accessibility. Clinically, the challenges for bone imaging include balancing the advantages of simple bone densitometry vs the more complex architectural features of bone or the deeper research requirements vs the broader clinical needs. The biological differences between the peripheral appendicular skeleton and the central axial skeleton must be further addressed. Finally, the relative merits of these sophisticated imaging techniques must be weighed with respect to their applications as diagnostic procedures, requiring high accuracy or reliability, compared with their monitoring applications, requiring high precision or reproducibility.

Prevrhal S. · Department of Radiology, University of California, San Francisco 94107, USA. · Radiologe. · Pubmed #17021911 No free full text.

Abstract: This article is an introduction to dual X-ray absorptiometry (DXA), the most widely used method today for diagnosis of osteoporosis. DXA can be used to assess projective bone mineral density at the lumbar spine, the proximal hip, and the whole body as well as the skeletal periphery at the forearm, the hand, and the heel. The prominent area of application of DXA is the diagnosis and monitoring of osteoporosis and its treatment. Because of its high accuracy, precision, and ability to predict osteoporotic fracture as well as its relatively low cost, DXA has prevailed over alternative methods. This article discusses the underlying X-ray physics and technological aspects, acquisition protocols, quality characteristics, and sources of error and their relevance. It also describes the various skeletal regions accessible to measurement, details on precision, nominal results, usability to predict fracture risk, and results of influential clinical trials.

Prevrhal S, Genant HK. · Osteoporosis and Arthritis Research Group, University of California, San Francisco 94143-1349, USA. · Radiologe. · Pubmed #10218212 No free full text.

Abstract: Quantitative computed tomography (QCT) can determine the true volumetric bone density of trabecular and cortical bone separately and at any skeletal site. QCT, because of its sensitivity to changes in bone status, is widely accepted as the superior method for the axial skeleton because of the high responsiveness of spinal trabecular bone to osteoporotic changes. The precision and accuracy of QCT at this site are somewhat lower than the respective values of other densitometric techniques. Nevertheless, because QCT measures a higher rate of bone loss at early premenopausal age, it allows better estimation of risk of vertebral fracture and smaller time intervals between follow-up measurements. The clinical acceptance of QCT is constrained by limited access to CT scanners for bone densitometry, the higher degree of operator dependence and the inability of QCT to measure the femur. New developments currently in scientific trial show that using volumetric CT can increase precision of QCT at the spine and allow highly accurate, precise and meaningful measurements at the femur.

Prevrhal S, Krege JH, Chen P, Genant H, Black DM. · Department of Epidemiology and Biostatistics, University of California-San Francisco, 185 Berry St., San Francisco, CA 94107, USA. · Curr Med Res Opin. · Pubmed #19250060 No free full text.

Abstract: OBJECTIVE: Most registration studies for new osteoporosis drugs have used a combination of quantitative morphometry (QM) and visual semiquantitative reading (SQ) to define vertebral fractures. However, in the pivotal teriparatide Fracture Prevention Trial (ClinicalTrials.gov Identifier: NCT00670501), vertebral fractures were previously defined only by the SQ methodology. The objective of this study was to define the effect of teriparatide on the incidence of vertebral fractures defined by QM plus SQ assessment. RESEARCH DESIGN AND METHODS: Radiographs from the Fracture Prevention Trial placebo- and teriparatide 20 microg/day groups were re-assessed in blinded fashion, defining incident vertebral fractures for vertebrae meeting all of the following requirements: (a) 20% decrease in height by QM, (b) a corresponding 4 mm decrease in height (c) an increase of at least one grade by visual SQ assessment by a radiologist. RESULTS: By this methodology, vertebral fracture risk was reduced in the teriparatide versus placebo group by 84% (RR = 0.16, p < 0.001). The risk of two or more vertebral fractures was also significantly reduced by 94% (RR = 0.06, p < 0.001). The fractures in the teriparatide group were of lesser severity than the fractures in the placebo group. The absolute benefit of teriparatide was greatest in those patients with the highest number and severity of prevalent vertebral fractures. CONCLUSIONS: As assessed by QM plus SQ, teriparatide reduced the incidence of vertebral fractures.

Prevrhal S, Shepherd JA, Faulkner KG, Gaither KW, Black DM, Lang TF. · Department of Radiology, UCSF, San Francisco, CA 94107, USA. · J Clin Densitom. · Pubmed #18280192 No free full text.

Abstract: Hip structural analysis (HSA) estimates geometrical and mechanical properties from hip dual-energy X-ray absorptiometry (DXA) images and is widely used in osteoporosis trials. This study compares HSA to volumetric quantitative computed tomography (QCT) measurements in the same population. A total of 121 women (mean age 58 yr, mean body mass index 27 kg/m2) participated. Each woman received a volumetric QCT scan and DXA scan of the left hip. QCT scans were analyzed with in-house software that directly computed geometric and mechanical parameters at the neck and trochanteric regions. DXA HSA was performed with an implementation by GE/Lunar. Pair-wise linear regression of HSA variables was conducted by method to site matched QCT variables for bone density, cross-sectional area, and cross-sectional moment of inertia (CSMI) of the femur neck. HSA correlated well with QCT (r2=0.67 for neck bone mineral density [BMD] and 0.5 for CSMI) and standard DXA at the neck (r2=0.82 for BMD). HSA and volumetric QCT compared favorably, which supports the validity of a projective technique such as DXA to derive geometrical properties of the proximal hip.

Bauer JS, Link TM, Burghardt A, Henning TD, Mueller D, Majumdar S, Prevrhal S. · Musculoskeletal and Quantitative Imaging Research, Department of Radiology, University of California in San Francisco, San Francisco, CA, USA. · Calcif Tissue Int. · Pubmed #17520165 No free full text.

Abstract: We investigated the influence of soft tissue (ST) on image quality by high-resolution multidetector computed tomography (MDCT) scans and assessed the effect of surrounding ST on the quantification of trabecular bone structure. Eight bone cores obtained from human proximal femoral heads discarded during hip replacement surgery were scanned with micro-computed tomography (microCT) as well as with MDCT both without (w/o) and with (w) simulated surrounding ST, where a phantom imitated a human torso. Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were measured in all scans. Apparent trabecular bone structure parameters were calculated and compared to similar parameters obtained in coregistered sections of the microCT scans. Residual errors were calculated as root-mean-square (RMS) errors relative to the microCT measurements. Compared to microCT results, trabecular structure parameters were overestimated by MDCT both w and w/o ST. SNR and CNR were significantly higher in the scans w/o ST. Significant correlations between microCT and MDCT results were found for bone fraction (r = 0.90 w/o ST, r = 0.84 w ST), trabecular number, and separation. RMS ranged from 10% to 15% for MDCT w/o ST and from 10% to 17% for MDCT w ST. Only bone fraction showed significantly different RMS and correlations for scans w/o vs. w ST (P < 0.05). This study showed that MDCT is able to visualize trabecular bone structure in an in vivo-like setting at skeletal sites within the torso such as the proximal femur. Even though ST scatter compromises image quality substantially, the major characteristics of the trabecular network can still be appreciated and quantified.

Patel PV, Prevrhal S, Bauer JS, Phan C, Eckstein F, Lochmüller EM, Majumdar S, Link TM. · Chicago Medical School, North Chicago, IL, USA. · J Comput Assist Tomogr. · Pubmed #15772547 No free full text.

Abstract: PURPOSE: To compare multislice computed tomography (MSCT)-derived parameters of the trabecular bone structure of the calcaneus with bone mineral density (BMD) in their ability to differentiate between donors with and without osteoporotic fractures of the spine and to optimize CT scan protocols. METHODS: Forty-two postmortem calcanei (81.2 +/- 10 years) were imaged with a 16-detector row MSCT system using 4 different scan protocols varying spatial resolution (12-24 lp/cm) and radiation dose. Structural parameters of trabecular bone were derived from these images, and BMDs of the calcanei were determined using dual x-ray absorptiometry. Vertebral deformities of the spine were radiographically classified using the Spinal Fracture Index. Diagnostic performance in differentiation between donors with and without vertebral fractures was assessed using receiver operating characteristic (ROC) analysis. RESULTS: There were significant case-control differences for many of the structural parameters measured (P < 0.05). The highest ROC values were found for apparent trabecular thickness using the high-resolution and high-dose protocols. Statistically significant correlations were found between most structure parameters and BMD (up to r = 0.85, P < 0.01). CONCLUSION: Structural parameters of trabecular bone as obtained from high-resolution MSCT images of the calcaneus can be used to differentiate between donors with and without osteoporotic vertebral fractures, using a high-resolution and high-dose CT protocol.

Prevrhal S, Meta M, Genant HK. · Osteoporosis and Arthritis Research Group, Department of Radiology, University of California, San Francisco, California 94143-1250, USA. · Osteoporos Int. · Pubmed #14598025 No free full text.

Abstract: To differentiate changes in trabecular and cortical bone density at a skeletal site bearing body weight, the main goal of this retrospective study was to develop and characterize two new regions of interest (ROIs) for DXA at the hip, one mainly focusing on trabecular bone and another mainly focusing on cortical bone. Specific aims were to maximize the precision of the ROIs and to characterize their usefulness for monitoring age-related bone loss and discriminating controls from fracture cases in a cross-sectional study population and to compare them with earlier ROIs designed by our group. The study used populations from two different previous studies conducted in our laboratory, with one comprising cohorts of healthy premenopausal women, healthy postmenopausal women, and postmenopausal osteoporotic women with at least one spinal fracture (Spine Fx Study) and the other one comprising two cohorts of age-matched postmenopausal women, in whom cases had sustained a hip fracture (Hip Fx study). The new ROI for trabecular bone (CIRCROI) tries to improve on the earlier custom-designed Central ROI, which was also targeted at trabecular bone. CIRCROI consists of an approximate largest circle that can fit inside the femoral proximal metaphysis without touching the superior and inferior endocortical walls. The new ROI for cortical bone (CORTROI) at a site bearing body weight is defined as a horizontal rectangular box crossing the femoral shaft below the lesser trochanter. CORTROI BMD cohort means were significantly higher than all other ROIs, and CIRCROI BMD cohort means were lower than standard ROIs with the exception of Ward's ROI. CIRCROI BMD was highly correlated with total femur BMD ( r=0.94) and Central BMD ( r=0.93), whereas CORTROI BMD correlations were lower (highest with total femur BMD ( r=0.86)). Fracture discrimination odds ratios (ORs) of all ROIs were significant for the Hip Fx Study, with CIRCROI BMD having the highest, and CORTROI BMD the lowest, OR (4.83 and 2.49 per SD, respectively, compared with 3.69 for Ward's ROI as the highest OR of standard ROIs). For the Spine Fx Study, only spinal and trochanteric BMD had significant OR. The new trabecular ROI had good short-term precision, comparable to the standard ROIs at the hip, but improving on that of Ward's triangle, the only standard ROI only including the anterior and posterior cortical walls and therefore more predominantly consisting of trabecular bone than other standard ROIs. The precision of the new cortical ROI was lower than standard DXA ROIs, except for Ward's triangle, but provides unique information on purely cortical bone at a skeletal site bearing body weight.

Prevrhal S, Fox JC, Shepherd JA, Genant HK. · Osteoporosis and Arthritis Research Group, Department of Radiology, University of California-San Francisco, San Francisco, California 94117, USA. · Med Phys. · Pubmed #12557971 No free full text.

Abstract: Measurement of the width of thin structures such as the cortical shell of the vertebral body or femoral neck with computed tomography (CT) is limited by the spatial resolution of the CT system. Limited spatial resolution exists both within the CT image plane and perpendicular to it and can be described by the in-plane point spread function (PSF) and the across-plane slice sensitivity profile (SSP), respectively. The goal of this study was to confirm that errors of thickness measurement of thin structures critically depend on the spatial positioning of the object and the spatial resolution limitations of CT in all three dimensions, and to assess the size of the errors themselves. We compared computer models that incorporated both effects to experimentally assessed cortical thicknesses of the European Spine Phantom. Analysis included varying CT slice width, the orientation of measurement and angle beta of misalignment of longitudinal scanner and phantom axes. Agreement of models with measurements was good in all configurations with an overall error of 0.17 mm. This showed that PSF and SSP are adequate system characteristics to predict deviation of measured values from true widths. Errors between measurements and true cortical thickness values delta(true) averaged to 1.5 mm were strongly positively correlated with slice width d and beta. When the across-plane partial volume effect was eliminated, limited in-plane resolution still accounted for overestimation of delta(true) by 0.68 (137%), 0.27 (27%), and 0.06 mm (4%) for delta(true)=0.5, 1.0, and 1.5 mm, respectively. For delta(true) of 1.0 mm and above, it was shown that although the absolute cortical thickness values might not be accurately measurable, relative differences between two values are reflected in measurement. Implications for cortical thickness measurement are that the spinal cortical shell is too thin, whereas accurate assessment at locations of the femoral neck exhibiting a thicker cortical shell of both difference and absolute values should be possible with CT even for larger misalignment angles, especially when a smaller CT slice width is chosen.

Prevrhal S, Fuerst T, Fan B, Njeh C, Hans D, Uffmann M, Srivastav S, Genant HK. · Osteoporosis and Arthritis Research Group, Department of Radiology, University of California, San Francisco, 350 Parnassus Avenue, Suite 607, San Francisco, CA 94143-1349, USA. · Osteoporos Int. · Pubmed #11305080 No free full text.

Abstract: This study investigated whether tibial speed of sound (SOS; SoundScan 2000, Myriad Ultrasound Systems, Israel) reflects not only bone mineral density (BMD) but also tibial cortical thickness, as assessed by dual-energy X-ray absorptiometry (DXA) and Quantitative CT (QCT) at a site-matched location. The secondary focus of the study was how tibial SOS compares with BMD at the spine and the hip, the most widely used locations for densitometry. Twenty-two young normal (N) and 23 postmenopausal women with spinal fractures (Fx) (mean (SD) age 35 (8) and 70 (5) years) underwent quantitative ultrasound (QUS) SOS measurement at the left tibial midshaft. From site-matched QCT scans (three 3-mm slices spaced along the QUS measurement region), BMD and cortical thickness were computed (QCT-cBMD, QCT-cTh). The cortex in the CT images was then subdivided into three concentric and equally spaced bands, and QCT-cBMD was computed separately for each band. DXA was performed at the mid-tibia (TIB BMD), at the spine (SPINE BMD) and the hip (total hip, HIP BMD). Correlation coefficients between parameters were determined with least-square linear fits. Intergroup differences were assessed by analysis of covariance, whose r2 value reflects the percentage variation in the data explained by group assignment. SOS correlated significantly with site-matched parameters (QCT-cBMD, OCT-cTh and TIB BMD, all r = 0.6, p < 0.001), SPINE BMD and HIP BMD (both r = 0.5, p < 0.001). Multiple regression with both QCT-cBMD and QCT-cTh against SOS yielded r = 0.7 with both parameters contributing significantly. For the cortex band subdivision, SOS correlated better with QCT-cBMD in the outermost band of the cortex (r = 0.67) than with the more central bands (r = 0.59 and r = 0.53). Group assignment could best explain SPINE BMD (r2 = 0.62) and HIP BMD (r2 = 0.51). SOS was comparable to TIB BMD (r2 = 0.3 vs. r2 = 0.35).: Our findings suggest that the tibial SOS measurement depends on both the thickness and density of the tibia, but is more strongly influenced by the density of the cortex near the surface than by its interior parts. The power of tibial ultrasound to discriminate between normal and fracture patients was less than that of spinal and femoral DXA BMD and comparable to site-matched DXA BMD.

Prevrhal S, Engelke K, Kalender WA. · Institute of Medical Physics, University of Erlangen, Germany. · Phys Med Biol. · Pubmed #10211808 No free full text.

Abstract: In this study we analysed the accuracy of computed tomography (CT) measurements in assessing cortical bone. We determined the dependency of thickness and density measurements on the true width and density of the cortex and on the spatial resolution in the CT images using two optimized segmentation methods. As a secondary goal, we assessed the ability of CT to reflect small changes in cortical thickness. Two different bone-mimicking phantoms with varying cortical thickness were scanned with single-slice CT on a Somatom Plus 4 scanner. Images were reconstructed with both a standard and a high-resolution convolution kernel. Two special operator-independent segmentation methods were used to automatically detect the edges of the cortical shell. We measured cortical thickness and density and compared the phantom measurements with theoretical computations by simulating a cross-sectional shape of the cortical shell. Based on the simulations, we calculated CT's power to detect small changes in cortical thickness. Simulations and phantom measurements were in very good agreement. Cortical thickness could be measured with an error of less than 10% if the true thickness was larger than 0.9 (0.7) mm for the standard (high-resolution) kernel which is close to the full width at half maximum (FWHM) of the point spread functions for these kernels and our scanner. Density measurements yielded errors of less than 10% for true cortical thickness values above two to three times the FWHM corresponding to 2.5 (2) mm in our case. The simulations showed that a 10% change in cortical width would not be detected with satisfying probability in bones with a cortical shell thinner than 1.2 mm. An accurate determination of the cortical thickness is limited to bones with a thickness higher than the FWHM of the scanner's point spread function. Therefore, the use of a high-resolution reconstruction kernel is crucial. Cortical bone mineral density can only be measured accurately in bones two to three times thicker than this number. In thinner bones, the measured density becomes dependent on the thickness. Changes in cortical thickness can only be assessed if the change is rather large or if the measured bone has sufficient thickness. Therefore, assessing density or thickness of the vertebral shell by CT should be treated with caution.