Stephan Grampp

Correlation of Trabecular Bone Structure with Age, Bone Mineral Density, and Osteoporotic Status: In Vivo Studies in the Distal Radius Using High Resolution Magnetic Resonance Imaging

High resolution magnetic resonance (MR) images of the distal radius were obtained at 1.5 Tesla in premenopausal normal, postmenopausal normal, and postmenopausal osteoporotic women. The image resolution was 156 μm in plane and 700 μm in the slice direction; the total imaging time was ∼16 minutes. An intensity‐based thresholding technique was used to segment the images into trabecular bone and marrow, respectively. Extensions of standard stereological techniques were used to derive measures of trabecular bone structure from these segmented images. The parameters calculated included apparent measures of trabecular bone volume fraction, trabecular thickness, trabecular spacing, and trabecular number. Fractal‐based texture parameters, such as the box‐counting dimension, were also derived. Trabecular bone mineral density (BMD) and cortical bone mineral content (BMC) were measured in the distal radius using peripheral quantitative computed tomography (pQCT). In a subset of patients, spinal trabecular BMD was measured using quantitative computed tomography (QCT). Correlations between the indices of trabecular bone structure measured from these high‐resolution MR images, age, BMD, and osteoporotic fracture status were examined. Cortical BMC and trabecular BMD at the distal radius, spinal BMD, trabecular bone volume fraction, trabecular thickness, trabecular number, and fractal dimension all decreased with age. Trabecular spacing showed the greatest percentage change and increased with age. In addition, significant differences were evident in spinal BMD, radial trabecular BMD, trabecular bone volume fraction, trabecular spacing, and trabecular number between the postmenopausal nonfracture and the postmenopausal osteoporotic subjects. Trabecular spacing and trabecular number showed moderate correlation with radial trabecular BMD but correlated poorly with radial cortical BMC. High resolution MR imaging, a potentially useful tool for quantifying trabecular structure in vivo, may have applications for understanding and evaluating skeletal changes related to age and osteoporosis.

Comparisons of Noninvasive Bone Mineral Measurements in Assessing Age‐Related Loss, Fracture Discrimination, and Diagnostic Classification

The purpose of this study was to examine the commonly available methods of noninvasively assessing bone mineral status across three defined female populations to examine their interrelationships, compare their respective abilities to reflect age‐ and menopause‐related bone loss, discriminate osteoporotic fractures, and classify patients diagnostically. A total of 47 healthy premenopausal (age 33 ± 7 years), 41 healthy postmenopausal (age 64 ± 9 years), and 36 osteoporotic postmenopausal (age 70 ± 6 years) women were examined with the following techniques: (1) quantitative computed tomography of the L1–L4 lumbar spine for trabecular (QCT TRAB BMD) and integral (QCT INTG BMD) bone mineral density (BMD); (2) dual X‐ray absorptiometry of the L1–L4 posterior‐anterior (DXA PA BMD) and L2–L4 lateral (DXA LAT BMD) lumbar spine, of the femoral neck (DXA NECK BMD) and trochanter (DXA TROC BMD), and of the ultradistal radius (DXA UD BMD) for integral BMD; (3) peripheral QCT of the distal radius for trabecular BMD (pQCT TRAB BMD) and cortical bone mineral content (BMC) (pQCT CORT BMC); (4) two radiographic absorptiometric techniques of the metacarpal (RA METC BMD) and phalanges (RA PHAL BMD) for integral BMD; and (5) two quantitative ultrasound devices (QUS) of the calcaneus for speed of sound (SOS CALC) and broadband ultrasound attenuation (BUA CALC). In general, correlations ranged from (r = 0.10−0.93) among different sites and techniques. We found that pQCT TRAB BMD correlated poorly (r ≤ 0.46) with all other measurements except DXA UD BMD (r = 0.62, p ≤ 0.0001) and RA PHAL BMD (r = 0.52, p ≤ 0.0001). The strongest correlation across techniques was between QCT INT BMD and DXA LAT BMD (r = 0.87, p ≤ 0.0001), and the weakest correlation within a technique was between pQCT TRAB BMD and pQCT CORT BMC (r = 0.25, p ≤ 0.05). Techniques showing the highest correlations with age in the healthy groups also showed the greatest differences among groups. They also showed the best discrimination (as measured by the odds ratios) for the distinction between healthy postmenopausal and osteoporotic postmenopausal groups based on age‐adjusted logistic regression analysis. For each anatomic site, the techniques providing the best results were: (1) spine, QCT TRAB BMD (annual loss, −1.2% [healthy premenopausal and healthy postmenopausal]); Students t‐value [not the T score], 5.4 [healthy postmenopausal vs. osteoporotic postmenopausal]; odds ratio, 4.3 [age‐adjusted logistic regression for healthy postmenopausal vs. osteoporotic postmenopausal]); (2) hip, DXA TROC BMD (−0.46; 3.5; 2.2); (3) radius, DXA UD BMD (−0.44; 3.3; 1.9) and pQCT, CORT BMC (−0.72; 2.9; 1.7); (4) hand, RA PHAL (−0.51; 3.6; 2.0); and (5) calcaneus, SOS (−0.09; 3.4; 2.1) and BUA (−0.52; 2.6; 1.7). Despite these performance trends, the differences among sites and techniques were statistically insignificant (p > 0.05) using age‐adjusted receiver operating characteristic (ROC) curve analysis. Nevertheless, kappa score analysis (using −2.0 T score as the cut‐off value for osteopenia and −2.5 T score for osteoporosis) showed that in general the diagnostic agreement among these measurements in classifying women as osteopenic or osteoporotic was poor, with kappa scores averaging about 0.4 (exceptions were QCT TRAB/INTG BMD, DXA LAT BMD, and RA PHAL BMD, with kappa scores ranging from 0.63 to 0.89). Often different patients were estimated at risk by using different measurement sites or techniques.

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.

Bone mineral density and biochemical parameters of bone metabolism in female patients with systemic lupus erythematosus

OBJECTIVE To evaluate bone mineral density and biochemical parameters of bone metabolism in ambulatory premenopausal female patients with systemic lupus erythematosus (SLE). METHODS 30 women who fulfilled the ARA criteria for the classification of SLE were studied. Lumbar and femoral bone mineral density was determined by dual energyx ray absorptiometry. Various laboratory parameters including serum calcium, serum phosphorus, alkaline phosphatase, bone specific isoform of alkaline phophatase, propeptide of type 1 procollagen, deoxypyridinoline excretion, telopeptide of type 1 collagen, serum creatinine, osteocalcin, parathyroid hormone, 25-OH vitamin D, testosterone, progesterone, estradiol, follicle stimulating hormone and luteinotropic hormone were measured. RESULTS According to the WHO criteria 39% of all patients with SLE studied had normal bone mineral density, 46% had osteopenia and 15% had osteoporosis at the lumbar spine; at the femoral neck 38.5% had normal bone mineral density, 38.5% had osteopenia and 23% suffered from osteoporosis. Significantly lower osteocalcin levels were found in SLE patients. All other bone resorption and formation markers measured were not statistically different, but higher serum albumin corrected calcium and lower phosphorus values were found in the SLE group. Of all sex hormones tested lower testosterone and higher follicle stimulating hormone concentrations were seen in patients with SLE. CONCLUSION A high incidence was found of osteopenia and osteoporosis in premenopausal patients with SLE. Bone diminution in SLE seems to be attributable, at least in part, to decreased bone formation in SLE patients.

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.

Fractal Analysis of Proximal Femur Radiographs: Correlation with Biomechanical Properties and Bone Mineral Density

Abstract: Conventional radiography and fractal analysis were used to quantify trabecular texture patterns in human femur specimens and these measures were used in conjunction with bone mineral density (BMD) to predict bone strength. Radiographs were obtained from 51 human femur specimens (25 male, 26 female). The radiographs were analyzed using three different fractal geometry based techniques, namely semi-variance, surface area and Fourier analysis. Maximum compressive strength (MCS) and shear stress (MSS) were determined with a material testing machine; BMD was measured using quantitative computed tomography (QCT). MCS and MSS both correlated significantly with BMD (MCS: R= 0.49–0.54; MSS: R= 0.69–0.72). Fractal dimension also correlated significantly with both biomechanical properties (MCS: R= 0.49–0.56; MSS: R= 0.47–0.54). Using multivariate regression analysis, the fractal dimension in addition to BMD improved correlations versus biomechanical properties. Both BMD and fractal dimension showed statistically significant correlation with bone strength. The fractal dimension provided additional information beyond BMD in correlating with biomechanical properties.

Accuracy and precision study in vitro for peripheral quantitative computed tomography.

We evaluated the accuracy and precision of a peripheral quantitative computed tomography (pQCT) scanner, the Stratec XCT-960, using 12 human cadaveric forearms. The accuracy was determined by comparing the total bone mineral content (BMC) with the ash weight (AW). We scanned and ashed three consecutive slices (thickness 2.5 mm) at the standard position (s-position) and at 2.5 mm both proximal and distal to the s-position. The correlation coefficient between the AW and total BMC using slices at the s-position wasr=0.87 with an accuracy error (random component) of 15.5%. The correlation coefficient using all slices wasr=0.90 with an accuracy error of 14.3%. The correlation coefficient improved tor=0.95 with an accuracy error of 9.7% after averaging the results of all three slices for each forearm. The short-term precision error expressed as the coefficient of variation (CV) of bone mineral density (BMD) and BMC was determined by measuring the forearms five times either with repositioning or without repositioning. The CVs with repositioning were 2.77 and 1.15 for total BMD and BMC, 1.85 for trabecular BMD; without repositioning they were 0.29, 0.58 and 0.69 respectively. To further evaluate the influence of positioning, additional scans were performed at 1, 2 and 5 mm proximal, and 1 and 2 mm distal to the s-position. BMD and BMC were greatly influenced by the scan location; for example, the percentage differences in trabecular BMD 1 mm distal and proximal relative to the s-position were 2.5%±5.1% and 0.18%±6.3%, respectively. The Stratec XCT-960 appears to be a moderately accurate and highly precise scanner with potential usefulness for evaluating BMC and BMD of ultradistal radius.

Analysis of trabecular bone structure in the distal radius using high-resolution MRI

The objective of this study was to develop high-resolution in vivo Magnetic resonance techniques to resolve the structure of trabecular bone in conjunction with image processing techniques to quantify variations in trabecular bone structure. Such techniques could then potentially be applied to assess osteoporotic changes and predict the risk fractures. Axial and coronal volumetric MRI images of the distal radius were obtained using a modified gradient echo sequence on a MRI images, on a 1.5 T imager at a spatial resolution of 150 μm and a slice thickness of 0.7 mm. Image thresholding techniques were used to identify trabecular bone and bone marrow: thereafter the area occupied by trabecular bone, mean trabecular width and mean intercept length as a function of angle were computed. An automatic boundary tracking algorithm was used to identify the bone and marrow interface. Fractal analysis was used to quantify the convolutedness of the marrow-trabecular bone interface. It is well known that the trabecular bone density is the greater at distal sites of the radius and decreases proximally. These variations were reflected by the decreases in the trabecular width. fractional area and fractal dimension. Over a 28 mm range, starting at 7 mm proximal from the joint line and extending 35 mm proximal to the joint line, the mean trabecular width decreased from 444.6 μm to 341.0, μm the fractional area of trabecular bone decreased from 0.44 to 0.15. and the fractal dimension decreased from 1.67 to 1.10. The choice of the threshold affected the quantification of the mean trabecular width and fractional trabecular bone area measurements, but the fractal dimension was more robust. High-resolution MRI images combined with image analysis techniques can he used to quantify structural variations in trabecular bone in the distal radius.

Interobserver variation in the detection of osteopenia by radiography and comparison with dual X-ray absorptiometry of the lumbar spine

In 100 patients (20 male, 80 female) radiographs of the lumbar spine were obtained in both planes, anteroposterior and lateral. Nine readers independently and without specific criteria or training assessed the radiographs for presence of osteopenia in the form of a binary decision. A posteroanterior dual x-ray absorptiometry (PA DXA) measurement of the lumbar spine was performed in all patients using the Hologic QDR 1000 bone densitometer. A bone mineral density (BMD) of 0.83 g/ cm2 (T-score about 2 SD and 2.5 SD lower than BMD in normal young female and male subjects respectively) was used as a threshold for the diagnosis of osteopenia. Complete agreement amongst the 9 readers was achieved in 43 patients. In 26 more patients at least 8 readers agreed, κ-coefficients for interobserver variation ranged from 0.458 to 0.691 for reader pairs. For agreement between the observer ratings and the DXA results, κ-coefficients ranging between 0.347 and 0.555 were found. The vast majority of readers agreed in the diagnosis of osteopenia in cases where the BMD was less than 0.73 g/cm2. Where the BMD was between 0.73 and 1.03 g/cm2 a substantial disagreement was found between reader evaluation and DXA measurement, and also amongst the readers. We conclude from our results that osteopenia can reliably be detected from lumbar spine radiographs by all readers only after a substantial amount of BMD is lost. On the other hand, a diagnosis based solely on PA DXA measurement of the spine may also lack accuracy, due to a substantial influence of degenerative changes of the lumbar spine and aortic calcification. Therefore, spine radiographs remain an important cornerstone in the detection and differential diagnosis of osteopenia.

Quantification and clinical relevance of head motion during computed tomography.

Objective:To quantify the 3-dimensional translation and rotation components of head motion during computed tomography and to analyze the influence of such motion on perceptible artifacts and distortion of volume image data sets. Methods:Using high-precision optoelectronic motion-capture technology, changes in patient head position during axial CT scanning were registered in 20 cases and 2 phantoms with a spatial relative resolution better than 0.003 cm. Statistical analysis was performed on a base of 6-dimensional measurement-vectors, each with 3 translation and 3 rotation values. Because of the recording frequency of the tracking system, more than 80,000 values were included in a statistical analysis. Results:All 20 patients had head motion during the CT scanning, with only 4 of 20 patients showing perceptible motion artifacts. The frequency, the extent, and the direction of the movements did not correlate with either the observations made by the radiologic staff or with the patient’s subjective estimation of comfort. Translation movements of the head during CT accounted for a maximum of 0.5 cm and rotations of more than 2° without perceptible motion artifacts. The extent of positional changes of the head was found to correlate with the duration of scanning (Pearson’s correlation coefficient: 0.647 for translation shifts, 0.453 for rotation shifts). The mean direction of head motion could be characterized predominantly as a rotation around the longitudinal axis of the body (xy plane) at a significance level of 0.01. Conclusion:Computed tomography evaluations of the head performed without rigid fixation suffer a spatial distortion of the volume image data sets, caused by interimage motion. The absence of motion artifacts is not correlated with the absence of motion.