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Genant, H. K.

Publications and source records attributed to Genant, H. K..

At least 19 records

Advanced imaging of the macrostructure and microstructure of bone

Noninvasive and/or nondestructive techniques are capable of providing more macro- or microstructural information about bone than standard bone densitometry. Although the latter provides important information about osteoporotic fracture risk, numerous studies indicate that bone strength is only partially explained by bone mineral density. Quantitative assessment of macro- and microstructural features may improve our ability to estimate bone strength. The methods available for quantitatively assessing macrostructure include (besides conventional radiographs) quantitative computed tomography (QCT) and volumetric quantitative computed tomography (vQCT). Methods for assessing microstructure of trabecular bone noninvasively and/or nondestructively include high-resolution computed tomography (hrCT), micro-computed tomography (muCT), high-resolution magnetic resonance (hrMR), and micromagnetic resonance (muMR). vQCT, hrCT and hrMR are generally applicable in vivo; muCT and muMR are principally applicable in vitro. Although considerable progress has been made in the noninvasive and/or nondestructive imaging of the macro- and microstructure of bone, considerable challenges and dilemmas remain. From a technical perspective, the balance between spatial resolution versus sampling size, or between signal-to-noise versus radiation dose or acquisition time, needs further consideration, as do the trade-offs between the complexity and expense of equipment and the availability and accessibility of the methods. The relative merits of in vitro imaging and its ultrahigh resolution but invasiveness versus those of in vivo imaging and its modest resolution but noninvasiveness also deserve careful attention. From a clinical perspective, the challenges for bone imaging include balancing the relative advantages of simple bone densitometry against the more complex architectural features of bone or, similarly, the deeper research requirements against the broader clinical needs. The considerable potential biological differences between the peripheral appendicular skeleton and the central axial skeleton have to be addressed further. Finally, the relative merits of these sophisticated imaging techniques have to be weighed with respect to their applications as diagnostic procedures requiring high accuracy or reliability on one hand and their monitoring applications requiring high precision or reproducibility on the other. Copyright 2000 S. Karger AG, Basel.

NASA Discipline Musculoskeletal

High resolution magnetic resonance imaging of the calcaneus: age-related changes in trabecular structure and comparison with dual X-ray absorptiometry measurements

A high-resolution magnetic resonance imaging (MRI) protocol, together with specialized image processing techniques, was applied to the quantitative measurement of age-related changes in calcaneal trabecular structure. The reproducibility of the technique was assessed and the annual rates of change for several trabecular structure parameters were measured. The MR-derived trabecular parameters were compared with calcaneal bone mineral density (BMD), measured by dual X-ray absorptiometry (DXA) in the same subjects. Sagittal MR images were acquired at 1.5 T in 23 healthy women (mean age: 49.3 +/- 16.6 [SD]), using a three-dimensional gradient echo sequence. Image analysis procedures included internal gray-scale calibration, bone and marrow segmentation, and run-length methods. Three trabecular structure parameters, apparent bone volume (ABV/TV), intercept thickness (I.Th), and intercept separation (I.Sp) were calculated from the MR images. The short- and long-term precision errors (mean %CV) of these measured parameters were in the ranges 1-2% and 3-6%, respectively. Linear regression of the trabecular structure parameters vs. age showed significant correlation: ABV/TV (r2 = 33.7%, P < 0.0037), I.Th (r2 = 26.6%, P < 0.0118), I.Sp (r2 = 28.9%, P < 0.0081). These trends with age were also expressed as annual rates of change: ABV/TV (-0.52%/year), I.Th (-0.33%/year), and I.Sp (0.59%/year). Linear regression analysis also showed significant correlation between the MR-derived trabecular structure parameters and calcaneal BMD values. Although a larger group of subjects is needed to better define the age-related changes in trabecular structure parameters and their relation to BMD, these preliminary results demonstrate that high-resolution MRI may potentially be useful for the quantitative assessment of trabecular structure.

NASA Discipline Number 26-10

Magnetic resonance imaging of the calcaneus: preliminary assessment of trabecular bone-dependent regional variations in marrow relaxation time compared with dual X-ray absorptiometry

RATIONALE AND OBJECTIVES: Marrow transverse relaxation time (T2*) in magnetic resonance (MR) imaging may be related to the density and structure of the surrounding trabecular network. We investigated regional variations of T2* in the human calcaneus and compared the findings with bone mineral density (BMD), as measured by dual X-ray absorpiometry (DXA). Short- and long-term precisions were evaluated first to determine whether MR imaging would be useful for the clinical assessment of disease status and progression in osteoporosis. METHODS: Gradient-recalled echo MR images of the calcaneus were acquired at 1.5 T from six volunteers. Measurements of T2* were compared with BMD and (for one volunteer) conventional radiography. RESULTS: T2* values showed significant regional variation; they typically were shortest in the superior region of the calcaneus. There was a linear correlation between MR and DXA measurements (r = .66 for 1/T2* versus BMD). Differences in T2* attributable to variations in analysis region-of-interest placement were not significant for five of the six volunteers. Sagittal MR images had short- and long-term precision errors of 4.2% and 3.3%, respectively. For DXA, the precision was 1.3% (coefficient of variation). CONCLUSION: MR imaging may be useful for trabecular bone assessment in the calcaneus. However, given the large regional variations in bone density and structure, the choice of an ROI is likely to play a major role in the accuracy, precision, and overall clinical efficacy of T2* measurements.

Non-NASA Center

Estimates of volumetric bone density from projectional measurements improve the discriminatory capability of dual X-ray absorptiometry

To determine whether estimates of volumetric bone density from projectional scans of the lumbar spine have weaker associations with height and weight and stronger associations with prevalent vertebral fractures than standard projectional bone mineral density (BMD) and bone mineral content (BMC), we obtained posteroanterior (PA) dual X-ray absorptiometry (DXA), lateral supine DXA (Hologic QDR 2000), and quantitative computed tomography (QCT, GE 9800 scanner) in 260 postmenopausal women enrolled in two trials of treatment for osteoporosis. In 223 women, all vertebral levels, i.e., L2-L4 in the DXA scan and L1-L3 in the QCT scan, could be evaluated. Fifty-five women were diagnosed as having at least one mild fracture (age 67.9 +/- 6.5 years) and 168 women did not have any fractures (age 62.3 +/- 6.9 years). We derived three estimates of "volumetric bone density" from PA DXA (BMAD, BMAD*, and BMD*) and three from paired PA and lateral DXA (WA BMD, WA BMDHol, and eVBMD). While PA BMC and PA BMD were significantly correlated with height (r = 0.49 and r = 0.28) or weight (r = 0.38 and r = 0.37), QCT and the volumetric bone density estimates from paired PA and lateral scans were not (r = -0.083 to r = 0.050). BMAD, BMAD*, and BMD* correlated with weight but not height. The associations with vertebral fracture were stronger for QCT (odds ratio [QR] = 3.17; 95% confidence interval [CI] = 1.90-5.27), eVBMD (OR = 2.87; CI 1.80-4.57), WA BMDHol (OR = 2.86; CI 1.80-4.55) and WA-BMD (OR = 2.77; CI 1.75-4.39) than for BMAD*/BMD* (OR = 2.03; CI 1.32-3.12), BMAD (OR = 1.68; CI 1.14-2.48), lateral BMD (OR = 1.88; CI 1.28-2.77), standard PA BMD (OR = 1.47; CI 1.02-2.13) or PA BMC (OR = 1.22; CI 0.86-1.74). The areas under the receiver operating characteristic (ROC) curves for QCT and all estimates of volumetric BMD were significantly higher compared with standard PA BMD and PA BMC. We conclude that, like QCT, estimates of volumetric bone density from paired PA and lateral scans are unaffected by height and weight and are more strongly associated with vertebral fracture than standard PA BMD or BMC, or estimates of volumetric density that are solely based on PA DXA scans.

Non-NASA Center

A two-year program of aerobics and weight training enhances bone mineral density of young women

Previous research suggests that physical activity may have a beneficial effect on bone mineral density (BMD) in women. This relationship was explored in a 2-year, randomized, intervention trial investigating the efficacy of exercise and calcium supplementation on increasing peak bone mass in young women. One hundred and twenty-seven subjects (ages of 20-35 years) were randomly assigned either to an exercise program that contained both aerobics and weight training components or to a stretching program. Calcium supplementation (up to 1500 mg/day including dietary intake) or placebo was given in a double-blinded design to all subjects. Spinal trabecular BMD was determined using quantitative computed tomography (QCT). Spinal integral, femoral neck, and trochanteric BMD were measured by dual X-ray absorptiometry (DXA) and calcaneal BMD by single photon absorptiometry (SPA). Fitness variables included maximal aerobic capacity (VO2max), and isokinetic muscle performance of the trunk and thigh. Measurements were made at baseline, 1 year, and 2 years. Sixty-three subjects (32 exercise, 31 stretching) completed the study, and all the measured bone parameters indicated a positive influence of the exercise intervention. There were significant positive differences in BMD between the exercise and stretching groups for spinal trabecular (2.5%), femoral neck (2.4%), femoral trochanteric (2.3%), and calcaneal (6.4%) measurements. The exercise group demonstrated a significant gain in BMD for spinal integral (1.3 +/- 2.8%, p < 0.02), femoral trochanteric (2.6 +/- 6.1%, p < 0.05), and calcaneal (5.6 +/- 5.1, p < 0.01) measurements. In contrast to exercise, the calcium intervention had no positive effect on any of the bone parameters. In regard to fitness parameters, the exercise group completed the study with significant gains in VO2max and isokinetic (peak torque) values for the knee flexion and extension and trunk extension. This study indicates that over a 2-year period, a combined regimen of aerobics and weight training has beneficial effects on BMD and fitness parameters in young women. However, the addition of daily calcium supplementation does not add significant benefit to the intervention.

Randomized Controlled Trial

Current methods and advances in bone densitometry

Bone mass is the primary, although not the only, determinant of fracture. Over the past few years a number of noninvasive techniques have been developed to more sensitively quantitate bone mass. These include single and dual photon absorptiometry (SPA and DPA), single and dual X-ray absorptiometry (SXA and DXA) and quantitative computed tomography (QCT). While differing in anatomic sites measured and in their estimates of precision, accuracy, and fracture discrimination, all of these methods provide clinically useful measurements of skeletal status. It is the intent of this review to discuss the pros and cons of these techniques and to present the new applications of ultrasound (US) and magnetic resonance (MRI) in the detection and management of osteoporosis.

Review, Academic

MRI of bone marrow in the distal radius: in vivo precision of effective transverse relaxation times

The effective transverse relaxation time T2* is influenced by the presence of trabecular bone, and can potentially provide a measure of bone density as well as bone structure. We determined the in vivo precision of T2* in repeated bone marrow measurements. The T2* measurements of the bone marrow of the distal radius were performed twice within 2 weeks in six healthy young volunteers using a modified water-presaturated 3D Gradient-Recalled Acquisition at Steady State (GRASS) sequence with TE 7, 10, 12, 20, and 30; TR 67; flip angle (FA) 90 degrees. An axial volume covering a length of 5.6 cm in the distal radius was measured. Regions of interest (ROIs) were determined manually and consisted of the entire trabecular bone cross-section extending proximally from the radial subchondral endplate. Reproducibility of T2* and area measurements was expressed as the absolute precision error (standard deviation [SD] in ms or mm2) or as the relative precision error (SD/mean x 100, or coefficient of variation [CV] in %) between the two-point measurements. Short-term precision of T2* and area measurements varied depending on section thickness and location of the ROI in the distal radius. Absolute precision errors for T2* times were between 1.3 and 2.9 ms (relative precision errors 3.8-9.5 %) and for area measurements between 20 and 55 mm2 (relative precision errors 5.1-16.4%). This MR technique for quantitative assessment of trabecular bone density showed reasonable reproducibility in vivo and is a promising future tool for the assessment of osteoporosis.

NASA Discipline Musculoskeletal

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 x UCSF] - 7.32).(ABSTRACT TRUNCATED AT 250 WORDS).

NASA Program Space Physiology and Countermeasures

Axial and appendicular bone density predict fractures in older women

To determine whether measurement of hip and spine bone mass by dual-energy x-ray absorptiometry (DEXA) predicts fractures in women and to compare the predictive value of DEXA with that of single-photon absorptiometry (SPA) of appendicular sites, we prospectively studied 8134 nonblack women age 65 years and older who had both DEXA and SPA measurements of bone mass. A total of 208 nonspine fractures, including 37 wrist fractures, occurred during the follow-up period, which averaged 0.7 years. The risk of fracture was inversely related to bone density at all measurement sites. After adjusting for age, the relative risks per decrease of 1 standard deviation in bone density for the occurrence of any fracture was 1.40 for measurement at the proximal femur (95% confidence interval 1.20-1.63) and 1.35 (1.15-1.58) for measurement at the spine. Results were similar for all regions of the proximal femur as well as SPA measurements at the calcaneus, distal radius, and proximal radius. None of these measurements was a significantly better predictor of fractures than the others. Furthermore, measurement of the distal radius was not a better predictor of wrist fracture (relative risk 1.64: 95% CI 1.13-2.37) than other sites, such as the lumbar spine (RR 1.56; CI 1.07-2.26), the femoral neck (RR 1.65; CI 1.12-2.41), or the calcaneus (RR 1.83; CI 1.26-2.64). We conclude that the inverse relationship between bone mass and risk of fracture in older women is similar for absorptiometric measurements made at the hip, spine, and appendicular sites.

Multicenter Study

Age-related decrements in bone mineral density in women over 65

Age-related changes in bone density contribute to the risk of fractures. To describe the relationship between age and bone mass in elderly women, we studied a large cohort of women over age 65 years who were recruited from population-based lists in four cities in the United States. Bone density in g/cm2 was measured by single-photon absorptiometry (SPA) and dual x-ray absorptiometry (DXA) at the distal and proximal radius, the calcaneus, the lumbar spine, and the proximal femur. Centralized data collection was used to control data quality and consistency. We found a strong inverse relationship between bone density and age for most sites. Decrements in bone density between women aged 65-69 years and women 85 years and older exceeded 16% in all regions except the spine, where the difference between the two age groups was 6%. Ward's triangle and the calcaneus exhibited the largest decrements, with 26 and 21%, respectively. The estimates of annual changes in bone mineral density by linear regression at sites other than the spine ranged from -0.82% at the femoral neck and trochanter to -1.30% at Ward's triangle. Correlations between the different regions ranged from r = 0.51 between the proximal radius and Ward's triangle to r = 0.66 between the distal radius and calcaneus. We conclude that the inverse relationship between age and bone mass measured by absorptiometry techniques in white women continues into the ninth decade of life. The relationship is strongest for bone density of Ward's triangle and the calcaneus and weakest for the spine.

NASA Discipline Musculoskeletal

Contribution of vertebral deformities to chronic back pain and disability. The Study of Osteoporotic Fractures Research Group

Among 2992 white women aged 65-70 years recruited from population-based listings, we measured radiographic vertebral dimensions of T5-L4 and calculated ratios of heights: anterior/posterior, mid/posterior, and posterior/posterior of either adjacent vertebra. The degree of deformity for each vertebra was analyzed in terms of the number of standard deviations (SD) that ratio differed from the mean ratio calculated for the same vertebral level in this population. We correlated the severity of each woman's worst vertebral deformity with back pain, back disability in six activities of daily living, and height loss since age 25. Only 39.4% of the cohort had no vertebral deformity; 10.2% had a deformity greater than or equal to 4 SD. Vertebral deformities less than 4 SD below the mean were not associated with increased back pain, disability, or loss of height. In contrast, women whose deformity was greater than or equal to 4 SD had a 1.9 (95% CI, 1.5-2.4) times higher risk of moderate to severe back pain and a 2.6 (95% CI, 1.7-3.9) times higher risk of disability involving the back; they were also 2.5 (95% CI, 2.0-3.2) times more likely to have lost greater than or equal to 4 cm in height. All three types of vertebral deformity (wedge, end plate, and crush) were equally associated with these outcomes. Multiple deformities less than 4 SD did not increase the likelihood of these three outcomes, but multiple deformities greater than or equal to 4 SD tended to be associated with increased back pain, disability, and height loss. This large cross-sectional study suggests that vertebral deformities cause substantial pain, disability, or loss of height only if vertebral height ratios fall 4 SD below the normal mean. Much back pain could not be attributed to vertebral deformities, suggesting other causes.

Non-NASA Center

Low-dosage micronized 17 beta-estradiol prevents bone loss in postmenopausal women

With the use of a double-blind, randomized, dose-ranging design, we tested during an 18-month period the degree of protection against postmenopausal bone loss afforded by micronized 17 beta-estradiol in dosages of 0.5, 1.0, and 2.0 mg. All subjects received supplementation to ensure a minimum of 1500 mg calcium daily. Fifty-one subjects completed at least 1 year of follow-up bone density measurements by quantitative computed tomography and by single- and dual-photon absorptiometry. In the placebo group spinal trabecular bone density decreased 4.9% annually (p less than 0.001), whereas in those taking micronized 17 beta-estradiol bone density tended to increase (annual increases of 0.3% in the 0.5 mg micronized 17 beta-estradiol group, 1.8% in the 1.0 mg micronized 17 beta-estradiol group, and 2.5% in the 2.0 mg micronized 17 beta-estradiol group). After completing the double-blind phase, 41 subjects completed an additional 18 months of follow-up while taking 1.0 mg micronized 17 beta-estradiol. During this time one third of the subjects were randomly assigned to discontinue calcium supplements. Among those who previously received placebo, trabecular bone density increased 4.3% annually, whereas among those who had used micronized 17 beta-estradiol, trabecular bone density response was inversely related to the dosage previously used. Additionally and independently, the level of calcium intake showed a statistically significant correlation with the change in spinal trabecular bone density (r = 0.37, p = 0.02). We conclude that micronized 17 beta-estradiol has a continuous skeletal dose-response effect in the range of 0.5 to 2.0 mg and that calcium intake positively modifies the skeletal response to 1.0 mg micronized 17 beta-estradiol.

Randomized Controlled Trial

Imaging of the hip joint. Computed tomography versus magnetic resonance imaging

The authors reviewed the applications and limitations of computed tomography (CT) and magnetic resonance (MR) imaging in the assessment of the most common hip disorders. Magnetic resonance imaging is the most sensitive technique in detecting osteonecrosis of the femoral head. Magnetic resonance reflects the histologic changes associated with osteonecrosis very well, which may ultimately help to improve staging. Computed tomography can more accurately identify subchondral fractures than MR imaging and thus remains important for staging. In congenital dysplasia of the hip, the position of the nonossified femoral head in children less than six months of age can only be inferred by indirect signs on CT. Magnetic resonance imaging demonstrates the cartilaginous femoral head directly without ionizing radiation. Computed tomography remains the imaging modality of choice for evaluating fractures of the hip joint. In some patients, MR imaging demonstrates the fracture even when it is not apparent on radiography. In neoplasm, CT provides better assessment of calcification, ossification, and periosteal reaction than MR imaging. Magnetic resonance imaging, however, represents the most accurate imaging modality for evaluating intramedullary and soft-tissue extent of the tumor and identifying involvement of neurovascular bundles. Magnetic resonance imaging can also be used to monitor response to chemotherapy. In osteoarthrosis and rheumatoid arthritis of the hip, both CT and MR provide more detailed assessment of the severity of disease than conventional radiography because of their tomographic nature. Magnetic resonance imaging is unique in evaluating cartilage degeneration and loss, and in demonstrating soft-tissue alterations such as inflammatory synovial proliferation.

Review

The effects of bone on proton NMR relaxation times of surrounding liquids

Preliminary attempts by our group at UCSF to assess fat content of vertebral marrow in the lumbar spine using relaxation time information demonstrated that the presence of trabecular bone affects relaxation times. The objective of this work was a thorough study of the effects of bone on NMR relaxation characteristics of surrounding liquids. Trabecular bone from autopsy specimens was ground up and sifted into a series of powders with graded densities ranging from 0.3 gm/cc to 0.8 gm/cc. Each powder was placed first in n-saline and then in cottonseed oil. With spectroscopy, spin-lattice relaxation times (T1) and effective spin-spin relaxation times (T2*) were measured for each liquid in each bone powder. As bone density and surface to volume ratio increased, T1 decreased faster for saline than for oil. T2* decreased significantly for both water and oil as the surface to volume ratio increased. It was concluded that effects of water on T1 could be explained by a surface interaction at the bone/liquid interface, which restricted rotational and translational motion of nearby molecules. The T1s of oil were not affected since oil molecules are nonpolar, do not participate in significant intermolecular hydrogen bonding, and therefore would not be expected to interact strongly with the bone surface. Effects on T2* could be explained by local magnetic field inhomogeneities created by discontinuous magnetic susceptibility near the bone surface. These preliminary results suggest that water in contact with trabecular bone in vivo will exhibit shortened relaxation times.

NASA Discipline Musculoskeletal

Quantitative computed tomography for spinal mineral assessment: current status

Quantitative CT (QCT) is an established method for the noninvasive assessment of bone mineral content in the vertebral spongiosum and other anatomic locations. The potential strengths of QCT relative to dual photon absorptiometry (DPA) are its capability for precise three-dimensional anatomic localization providing a direct density measurement and its capability for spatial separation of highly responsive cancellous bone from less responsive cortical bone. The extraction of this quantitative information from the CT image, however, requires sophisticated calibration and positioning techniques and careful technical monitoring.

Lumbar Vertebrae/radiography

Assessment of metabolic bone diseases by quantitative computed tomography

Advances in the radiologic sciences have permitted the development of numerous noninvasive techniques for measuring the mineral content of bone, with varying degrees of precision, accuracy, and sensitivity. The techniques of standard radiography, radiogrammetry, photodensitometry, Compton scattering, neutron activation analysis, single and dual photon absorptiometry, and quantitative computed tomography (QCT) are described and reviewed in depth. Results from previous cross-sectional and longitudinal QCT investigations are given. They then describe a current investigation in which they studied 269 subjects, including 173 normal women, 34 patients with hyperparathyroidism, 24 patients with steroid-induced osteoporosis, and 38 men with idiopathic osteoporosis. Spinal quantitative computed tomography, radiogrammetry, and single photon absorptiometry were performed, and a spinal fracture index was calculated on all patients. The authors found a disproportionate loss of spinal trabecular mineral compared to appendicular mineral in the men with idiopathic osteoporosis and the patients with steroid-induced osteoporosis. They observed roughly equivalent mineral loss in both the appendicular and axial regions in the hyperparathyroid patients. The appendicular cortical measurements correlated moderately well with each other but less well with spinal trabecular QCT. The spinal fracture index correlated well with QCT and less well with the appendicular measurements. Knowledge of appendicular cortical mineral status is important in its own right but is not a valid predictor of axial trabecular mineral status, which may be disproportionately decreased in certain diseases. Quantitative CT provides a reliable means of assessing the latter region of the skeleton, correlates well with the spinal fracture index (a semiquantitative measurement of end-organ failure), and offers the clinician a sensitive means of following the effects of therapy.

Minerals/analysis