Integral Bone Mineral Density Research Articles

Changing structure of the femoral neck across the adult female lifespan

The anatomic distribution of cortical and cancellous bone in the femoral neck may be critical in determining resistance to fracture. We investigated the effects of aging on femoral neck bone in women. In this cross-sectional study, we used clinical multidetector computed tomography (MDCT) of the hips to investigate aging effects in 100 female volunteers aged 20 to 90 years. We developed a clinically efficient protocol to measure cortical thickness (C.Th) and cortical, trabecular, and integral bone mineral density (CtBMD, TrBMD, and iBMD in mg/cm(3)) in anatomic quadrants of the femoral neck. We used a nested ANOVA to evaluate their associations with height, weight, location in the femoral neck, and age of the subject. Age was the principal determinant of both cortical thickness and BMD. Age had significantly different effects within the anatomic quadrants; compared with young women, elderly subjects had relative preservation of the inferoanterior (IA) quadrant but strikingly reduced C.Th and BMD superiorly. A model including height, weight, and region of interest (and their interactions) explained 83% of the measurement variance (p < .0001). There were marked C.Th and BMD differences between age 25 and age 85 in the already thin superior quadrants. At 25 years the predicted C.Th of the superoposterior quadrant was 1.63 mm, whereas at 85 years it was 0.33 mm [-1.33 mm, 95% confidence interval (CI) of difference over 60 years -1.69 to -0.95]. By contrast, at 25 years mean C.Th of the IA quadrant was 3.9 mm, whereas at 85 years it was 3.3 mm (-0.6 mm, 95% CI -0.83 to -0.10). CtBMD of the IA region was equivalent at 25 and 85 years. In conclusion, elderly women had relative preservation of IA femoral neck bone over seven decades compared with young women but markedly lower C.Th and BMD in the other three quadrants. The IA quadrant transmits mechanical load from walking. Mechanical theory and laboratory tests on cadaveric femurs suggest that localized bone loss may increase the risk of fracture in elderly fallers. It remains to be determined whether this MDCT technique can provide better prediction of hip fracture than conventional clinical dual X-ray absorptiometry (DXA).

Quantitative Computed Tomography Reveals the Effects of Race and Sex on Bone Size and Trabecular and Cortical Bone Density

To examine the effects of race and sex on bone density and geometry at specific sites within the proximal femur and lumbar spine, we used quantitative computed tomography to image 30 Caucasian American (CA) men, 25 African American (AA) men, 30 CA women, and 17 AA women aged 35–45 yr. Volumetric integral bone mineral density (BMD), trabecular BMD (tBMD), and cross sectional area were measured in the femoral neck, trochanter, total femur, and L1/L2 vertebrae. Volumetric cortical BMD (cBMD) was also measured in the femur regions of interest. Differences were ascertained using a multivariate regression model. Overall, AA subjects had denser bones than CA subjects, but there were no racial differences in bone size. Men had larger femoral necks but not larger vertebrae than women. The AA men had higher tBMD and cBMD in the femur than CA men, whereas AA women had higher femoral tBMD but not higher femoral cBMD than CA women. These data support the idea that higher hip fracture rates in women compared with men are associated with smaller bone size. Lower fracture rates in AA elderly compared with CA elderly are consistent with higher peak bone density, particularly in the trabecular compartment, and potentially lower rates of age-related bone loss rather than larger bone size.

Quantitative Computed Tomography-Based Predictions of Vertebral Strength in Anterior Bending

This study examined the ability of QCT-based structural assessment techniques to predict vertebral strength in anterior bending. The purpose of this study was to compare the abilities of QCT-based bone mineral density (BMD), mechanics of solids models (MOS), e.g., bending rigidity, and finite element analyses (FE) to predict the strength of isolated vertebral bodies under anterior bending boundary conditions. Although the relative performance of QCT-based structural measures is well established for uniform compression, the ability of these techniques to predict vertebral strength under nonuniform loading conditions has not yet been established. Thirty human thoracic vertebrae from 30 donors (T9-T10, 20 female, 10 male; 87 +/- 5 years of age) were QCT scanned and destructively tested in anterior bending using an industrial robot arm. The QCT scans were processed to generate specimen-specific FE models as well as trabecular bone mineral density (tBMD), integral bone mineral density (iBMD), and MOS measures, such as axial and bending rigidities. Vertebral strength in anterior bending was poorly to moderately predicted by QCT-based BMD and MOS measures (R2 = 0.14-0.22). QCT-based FE models were better strength predictors (R2 = 0.34-0.40); however, their predictive performance was not statistically different from MOS bending rigidity (P > 0.05). Our results suggest that the poor clinical performance of noninvasive structural measures may be due to their inability to predict vertebral strength under bending loads. While their performance was not statistically better than MOS bending rigidities, QCT-based FE models were moderate predictors of both compressive and bending loads at failure, suggesting that this technique has the potential for strength prediction under nonuniform loads. The current FE modeling strategy is insufficient, however, and significant modifications must be made to better mimic whole bone elastic and inelastic material behavior.

Comparison of quantitative computed tomography-based measures in predicting vertebral compressive strength

Patient-specific measures derived from quantitative computed tomography (QCT) scans are currently being developed as a clinical tool for vertebral strength prediction. QCT-based measurement techniques vary greatly in structural complexity and generally fall into one of three categories: (1) bone mineral density (BMD), (2) “mechanics of solids” (MOS) models, such as minimum axial rigidity (the product of axial stiffness and vertebral height), or (3) three-dimensional finite element (FE) models. There is no clear consensus as to the relative performance of these measures due to differences in experimental protocols, sample sizes and demographics, and outcome metrics. The goal of this study was to directly compare the performance of QCT-based assessment techniques of varying degrees of structural sophistication in predicting experimental vertebral compressive strength. Eighty-one human thoracic vertebrae (T6–T10) from 44 donors cadavers ( F = 32, M = 12; 85 ± 8 years old, max = 97 years old, min = 54 years old) were QCT scanned and destructively tested in uniaxial compression. The QCT scans were processed to generate FE models and various BMD and MOS measures, including trabecular bone mineral density (tBMD), integral bone mineral density (iBMD), and axial rigidity. Bone mineral density was weakly to moderately predictive of compressive strength ( R 2 = 0.16 and 0.62 for tBMD and iBMD, respectively). In vitro vertebral strength was strongly correlated with both axial rigidity ( R 2 = 0.81) and FE strength measurements ( R 2 = 0.80), and the predictive capabilities of these two metrics were statistically equivalent ( p > 0.05 for differences between FE and axial rigidity). The results of this study indicate that non-invasive predictive measures of vertebral strength should include some level of structural sophistication, specifically, gross geometric and material property distribution information. For uniaxial compression of isolated vertebrae, which is the current biomechanical testing paradigm for new non-invasive strength assessment techniques, QCT-based FE and axial rigidity measures are equivalent predictors of experimental strength. However, before abandoning the FE method in favor of more simplistic techniques, future work should investigate the performance of the FE method versus MOS measures for more physiologically representative loading conditions, e.g., anterior bending or in situ loading with intervertebral discs intact.

Regional trabecular morphology assessed by micro-CT is correlated with failure of aged thoracic vertebrae under a posteroanterior load and may determine the site of fracture

Introduction Spinal mobilization is commonly used in the treatment of patients with back pain, including individuals with osteoporosis. Previous data indicated that traditional predictors of skeletal failure–lateral or anteroposterior bone mineral density (BMD) by dual energy X-ray absorptiometry (DXA) or geometry of the spinous process or vertebral body–do not predict failure load during posteroanterior spinal mobilization. Morphological differences and inhomogeneities in BMD may have important effects on vertebral strength but integral BMD values by DXA cannot reflect these potentially important differences. We investigated the determinants of spinal fracture using μCT. Materials and methods We measured failure load and failure site in 11 T5–8 cadaveric specimens (mean age 78 years) when a posteroanterior load was applied at the spinous process of T6 using a servohydraulic material testing machine. Radiography and CT scan were used to verify failure site. We observed no damage to the adjacent T7 vertebrae following the T6 posteroanterior failure test. The T7 vertebrae were sectioned to produce regional samples of the spinous process, the lamina and a vertebral body core. Each sample was scanned with μCT to measure bone microarchitectural parameters. We segmented and analysed four trabecular regions (spinous process base and middle, central lamina and central vertebral body). We used one-way repeated measures ANOVA to compare regions and computed Pearson correlations to assess the relation between PA failure load of T6 and the morphological parameters of T7. Results The BV/TV at the base or middle of the T7 spinous process (fracture sites), Tb.N and Tb.Th at the base were significantly correlated with posteroanterior failure load of T6 (BV/TV base: r = 0.74, p = 0.01; BV/TV middle: r = 0.73, p = 0.01; Tb.N base: r = 0.64, p = 0.03; Tb.Th base: r = 0.65, p = 0.03). The Tb.Th of the lamina was significantly greater than Tb.Th of the spinous process base ( p = 0.002). Conclusions Whereas previous data indicated that BMD by DXA was not a good predictor of posteroanterior failure load, regional BV/TV of the spinous process base and middle regions, the sites of fracture, are correlated with posteroanterior failure load. Trabecular thickness differed significantly between the base of the spinous process and the lamina, and may have influenced the site of fracture.

Influence of anthropometric parameters and bone size on bone mineral density using volumetric quantitative computed tomography and dual X-ray absorptiometry at the hip

To evaluate the influence of anthropometric parameters (age, height, and weight) and bone size on bone mineral density (BMD) using volumetric quantitative computed tomography (QCT) and dual X-ray absorptiometry (DXA) in a group of elderly women. BMD values were obtained with DXA and QCT at the spine and hip in a cohort of 84 elderly women (mean age 73 +/- 6 years). QCT measures included trabecular, integral, and cortical BMD assessed at the hip and spine as well as cross-sectional areas of the mid-vertebrae and proximal femora. Spinal integral and femoral neck BMD measures were well matched to the regions of bone quantified on anteroposterior (AP) spine DXA and the femoral neck region of hip DXA. When QCT parameters were linearly regressed against body height and weight, only the relationships with weight were found to be statistically significant. Except for cortical BMD at the femoral neck, all BMD and geometric parameters measured from both DXA and QCT showed statistically significant associations with body weight (r2 = 0.4, 0.0001 < P < 0.02). The strongest associations with weight were found for DXA Neck (DXA_NECK) and DXA lumbar spine (DXA_LSP) (r2 = 0.4, P < 0.0001). The relationship of DXA BMD is stronger than QCT BMD with body weight and it encompasses the response of both bone size and density to increasing body mass.

Effect of spinal degenerative changes on volumetric bone mineral density of the central skeleton as measured by quantitative computed tomography

To evaluate the impact of degenerative changes due to osteoarthritis (OA) at the spine on volumetric bone mineral density (BMD) as measured by volumetric quantitative computed tomography (vQCT). Eighty-four elderly women (mean age 73 +/- 6 years), comprising 33 with vertebral fractures assessed by radiographs and 51 without vertebral fractures, were studied. Trabecular, cortical, and integral BMD were examined at the spine and hip using a helical CT scanner and were compared to dual X-ray absorptiometry (DXA) measurements at the same sites. OA changes visible on the radiographs were categorized into two grades according to severity. Differences in BMD measures obtained in the two groups of patients defined by OA grade using the described radiologic methods were compared using analysis of variance. Standardized difference (effect sizes) was also compared between radiologic methods. Spinal trabecular BMD did not differ significantly between OA grade 0 and OA grade 1. Spinal cortical and integral BMD measures showed statistically significant differences, as did the lumbar spine DXA BMD measurement (13%, P = 0.02). The QCT measurements at the hip were also higher in OA 1 subjects. Femoral trabecular BMD was 13-15% higher in OA grade 1 subjects than in OA grade 0 subjects. The cortical BMD measures in the CT_TOT_FEM and CT_TROCH ROI's were also higher in the OA 1 subjects. The integral QCT BMD measures in the hip showed difference between grades OA 1 and 0. The DXA measurements in the neck and trochanter ROI's showed smaller differences (9 and 11%, respectively). There were no statistically significant differences in bone size. There is no evidence supporting that trabecular BMD measurements by QCT are influenced by OA. Instead, degenerative changes have an effect on both cortical and integral QCT, and on DXA at the lumbar spine and the hip. For subjects with established OA, assessment of BMD by volumetric QCT may be suggested.

Lack of Efficacy of Low-Intensity Pulsed Ultrasound on Prevention of Postmenopausal Bone Loss Evaluated at the Distal Radius in Older Chinese Women

A within-subject, randomized, and prospective intervention trial was done to evaluate the potential effect of low-intensity pulsed ultrasound on prevention of postmenopausal bone loss. Twenty healthy postmenopausal women between the ages of 51-81 years met the inclusion criteria. The treatment hand was randomly selected, and the contralateral site served as a control. Integral and trabecular bone mineral density were measured using highly precise multilayer peripheral quantitative computed tomography at the bilateral distal radius at baseline, 3 months after daily low-intensity pulsed ultrasound treatment, and 3 months after discontinuing treatment. Results showed that the rate of bone change (trabecular bone mineral density and integral bone mineral density) did not significantly differ between the site treated with low-intensity pulsed ultrasound and the contralateral control at either followup. Also, during the followup, bone mineral density did not change significantly in the contralateral control site. This was the first prospective and randomized study to show that low-intensity pulsed ultrasound at the current regime did not have significant effects on intact bone for prevention of postmenopausal bone loss in the distal radii of older Chinese women.

Correlations of calcaneal QUS with pQCT measurements at distal tibia and non-weight-bearing distal radius.

Quantitative ultrasound (QUS) is used for prediction for risks of osteoporotic fractures at various skeletal sites, irrespective of weight-bearing or non-weight-bearing skeletons. In the current study, we investigated the correlation between calcaneal QUS measurements (BUA, VOS, and Soundness) and volumetric trabecular, cortical, and its integral bone mineral density (tBMD, cBMD, and iBMD) using peripheral quantitative computed tomography (pQCT) of the weight-bearing distal tibia and non-weight-bearing distal radius in 198 healthy Chinese women between 40 and 62 years of age. Results showed that BUA, VOS, and Soundness measured by calcaneal QUS were significantly correlated with tBMD, cBMD, and iBMD of both distal tibia and distal radius (r = 0.210-0.447; all P < 0.01). The correlation coefficients of all the individual parameters between calcaneus and distal tibia were correspondingly higher (r = 0.214-0.447; all P < 0.01) than that of distal radius (r = 0.210-0.368; all P < 0.01). QUS Soundness showed the highest correlation (r = 0.447; P < 0.01) with tBMD of distal tibia when comparing with all other parameters between these two measurement devices. Stronger "within-device" correlations (r = 0.640-0.764; all P < 0.01) were found in pQCT measurements between distal tibia and radius. In addition, the largest and significant age-related decline was found in tBMD of the distal radius measured by pQCT and Soundness of the QUS measurement in the postmenopausal group. In conclusion, heel QUS measurement demonstrated slightly better correlation with trabecular bone of the weight-bearing skeleton than that of the non-weight-bearing skeleton measured by pQCT.

Trabecular and integral bone density in adults with sickle cell disease.

Sickle cell disease (SCD) is a hereditary disorder of hemoglobin synthesis that can affect the skeletal system owing to accelerated hematopoiesis and/or bone infarction. Additionally, several studies have suggested that a low bone mass is associated with SCD, partly because of adverse effects on growth and development. The few previous studies of bone mineral density (BMD) in these patients have utilized dual-photon or dual-energy x-ray absorptiometric (DXA) techniques, which may have limited value in this population because it cannot correct for differences in bone size. We undertook a study of BMD in the forearm of patients with sickle cell disease using peripheral quantitative computed tomography (QCT), which provides a measure of volumetric bone density for the trabecular bone component as well as cortical and trabecular bone together. We studied 32 African-American SCD patients with no known history of bone infarction in the wrist, and compared them with data from healthy African-American volunteers. We found a 13% lower integral (cortical and trabecular) BMD in the SCD patients (p=0.001), but no difference in trabecular BMD (p=0.40 for males, 0.32 for females). We hypothesize that the maintenance of trabecular BMD in the wrist may be related to the persistence of metabolically active red marrow in this region in adults with SCD.

Baseline BMD and bone loss at distal radius measured by peripheral quantitative computed tomography in peri- and postmenopausal Hong Kong Chinese women.

The current study was designed to investigate the rate of bone loss in distal radius and its association with baseline volumetric bone mineral density (BMD) and years since menopause (YSM) in peri- and postmenopausal women using precise and multislice peripheral quantitative computed tomography (pQCT; Densiscan 2000). Two hundred and five healthy Hong Kong Chinese perimenopausal ( n = 26) and postmenopausal ( n = 179) women within 10 years of the onset of menopause were recruited. Anthropometric parameters and menstrual status were also measured. The linear regression model derived from the baseline volumetric BMD revealed a significant and slightly better correlation with YSM than age, with a YSM-related annual decline of 2.56%, 1.82% and 0.65% in trabecular BMD (tBMD), integral BMD (iBMD) and cortical BMD (cBMD), respectively. Follow-up measurements after a time interval of 12 months showed that the rate of bone loss was higher than the annual decline in BMD calculated from the baseline BMD, with decreases of 2.89%, 2.16% 0.91% in tBMD, iBMD and cBMD, respectively. Baseline BMD was associated with age or YSM ( r ranges from -0.283 to -0.502; p<0.001 in all cases), but no relationship was found between annual rate of bone loss and age or YSM. The rate of bone loss did not correlate with baseline volumetric BMD values or YSM after dividing the subjects into fast bone losers (with annual tBMD loss > or =3%), normal bone losers (with annual tBMD loss > or = 1% but <3%) or slow bone losers (with annual tBMD loss <1%). The rate of bone loss was greater in both trabecular and cortical bone of postmenopausal women within the first 3 menopausal years but was only significant in the iBMD as compared with perimenopausal and postmenopausal women over 7 years after onset of menopause. The percentage distribution of slow and fast bone losers was not found to be associated with YSM. As a total of only 4 fracture cases were documented, the study could not provide conclusive information on whether perimenopausal and early postmenopausal baseline volumetric BMD or rate of bone loss determines the development of osteoporosis or fracture occurrence.

Measurement of bone mineral density at the spine and proximal femur by volumetric quantitative computed tomography and dual-energy x-ray absorptiometry in elderly women with and without vertebral fractures

The goal of this study was to determine the effect of vertebral fracture status on trabecular bone mineral density (BMD) measurements obtained in the proximal femur and spine by helical volumetric quantitative computed tomography (vQCT). The study population consisted of 71 Italian women (average age 73 ± 6) years. This group included 26 subjects with radiographically confirmed atraumatic vertebral fractures and 45 controls. The subjects received helical CT scans of the L1 and L2 vertebral bodies and the hip. The three-dimensional CT images were processed using specialized image analysis algorithms to extract measurements of trabecular, cortical, and integral BMD in the spine and hip. To compare the vQCT results with the most widely used clinical BMD measurement, dual X-ray absorptiometry (DXA) scans of the anteroposterior (AP) spine and proximal femur were also obtained. The difference between the subjects with vertebral fractures and the age-matched controls was computed for each BMD measure. All BMD measurements showed statistically significant differences, which ranged from 7% to 22% between subjects with fractures and controls. Although, given our small sample size, we could not detect statistically significant differences in discriminatory power between BMD techniques, integral BMD of the spine measured by vQCT and DXA tended to show stronger associations with fracture status (0.001 < p < 0.004). Measurements by QCT and DXA at the hip were also associated with vertebral fracture status, although the association of DXA BMD with fracture status was explained largely by differences in body weight between subjects with vertebral fractures and controls.

Digital topological analysis of in vivo magnetic resonance microimages of trabecular bone reveals structural implications of osteoporosis.

Osteoporosis is a disease characterized by bone volume loss and architectural deterioration. The majority of work aimed at evaluating the structural implications of the disease has been performed based on stereologic analysis of histomorphometric sections. Only recently noninvasive imaging methods have emerged that provide sufficient resolution to resolve individual trabeculae. In this article, we apply digital topological analysis (DTA) to magnetic resonance microimages (mu-MRI) of the radius obtained at 137 x 137 x 350 microm3 voxel size in a cohort of 79 women of widely varying bone mineral density (BMD) and vertebral deformity status. DTA is a new method that allows unambiguous determination of the three-dimensional (3D) topology of each voxel in a trabecular bone network. The analysis involves generation of a bone volume fraction map, which is subjected to subvoxel processing to alleviate partial volume blurring, followed by thresholding and skeletonization. The skeletonized images contain only surfaces, profiles, curves, and their mutual junctions as the remnants of trabecular plates and rods after skeletonization. DTA parameters were compared with integral BMD in the lumbar spine and femur as well as MR-derived bone volume fraction (BV/TV). Vertebral deformities were determined based on sagittal MRIs of the spine with a semiautomatic method and the number of deformities counted after threshold setting. DTA structural indices were found the strongest discriminators of subjects with deformities from those without deformities. Subjects with deformities (n = 29) had lower topological surface (SURF) density (p < 0.0005) and surface-to-curve ratio (SCR; a measure of the ratio of platelike to rodlike trabeculae; p < 0.0005) than those without. Profile interior (PI) density, a measure of intact trabecular rods, was also lower in the deformity group (p < 0.0001). These data provide the first in vivo evidence for the structural implications inherent in postmenopausal osteoporosis accompanying bone loss, that is, the conversion of trabecular plates to rods and disruption of rods due to repeated osteoclastic resorption.

Trabecular bone volume fraction mapping by low-resolution MRI.

Trabecular bone volume fraction (TBVF) is highly associated with the mechanical competence of trabecular bone. TBVF is ordinarily measured by histomorphometry from bone biopsies or, noninvasively, by means of high-resolution microcomputed tomography and, more recently, by micro-MRI. The latter methods require spatial resolution sufficient to resolve trabeculae, along with segmentation techniques that allow unambiguous assignment of the signal to bone or bone marrow. In this article it is shown that TBVF can be measured under low-resolution conditions by exploiting the attenuation of the MR signal resulting from fractional occupancy of the imaging voxel by bone and bone marrow, provided that a reference signal is available from a marrow volume devoid of trabeculation. The method requires accurate measurement of apparent proton density, which entails correction for various sources of error. Key among these are the spatial nonuniformity in the RF field amplitude and effects of the slice profile, which are determined by B(1) field mapping and numerical integration of the Bloch equations, respectively. By contrast, errors from variations in bone marrow composition (hematopoietic vs. fatty) between trabecular and reference site are predicted to be small and usually negligible. The method was evaluated in phantoms and in vivo in the distal radius and found to be accurate to 1% in marrow volume fraction. Finally, in a group of 12 patients of varying skeletal status, TBVF in the calcaneus was found to strongly correlate with integral bone mineral density of the lumbar vertebrae (r(2) = 0.83, p < 0.0001). The method may fail in large imaging objects such as the human trunk at high magnetic field where standing wave and RF penetration effects cause intensity variations that cannot be corrected. Magn Reson Med 46:103-113, 2001.

Age, sex, and grip strength determine architectural bone parameters assessed by peripheral quantitative computed tomography (pQCT) at the human radius

The purpose of this study was to estimate the relation of some noninvasively derived mechanical characteristics of radial bone including architectural parameters for bone strength to grip strength and muscle cross-section. Sixty-three males between 21 and 78 yr of age and 101 females between 18 and 80 yr of age were measured at the nondominant forearm using peripheral quantitative computed tomography (pQCT). We assessed the integral bone mineral density (BMD I) and content (BMC I) by pQCT at the distal and at the mid-shaft radius. Integral bone area (Area I), cortical thickness (C-th), and a newly proposed index for bone strength; the stress–strain index (SSI) were also calculated. The dynamometrically measured maximum grip strength was taken as a mechanical loading parameter and muscle cross-section as a substitute for it. Sex, grip strength, BMC I and BMD I (distal radius) were identified in a multiple regression analysis to significantly predict bone strength as expressed by SSI, after adjusting for all other independent variables, including age and sex ( p<0.0001). Grip strength was closest related to age, sex, BMD I and SSI p of the distal radius. The cross-sectional area of muscle was not significantly determining the grip strength within the analysis model. In conclusion, our results suggested that architectural parameters at the distal radius were better related to grip strength than to cross-sectional muscle area in both males and females. Maximum muscle strength as estimated by grip strength might be a stronger determinant of mechanical characteristics of bones as compared with cross-sectional muscle area.

Estimation of the architectural properties of cortical bone using peripheral quantitative computed tomography.

We assessed the volumetric bone mineral density (vBMD) and cross-sectional architecture of cortical bone at the distal radius by peripheral quantitative computed tomography (pQCT). The volumetric bone mineral density [integral bone mineral density (BMDi), trabecular bone mineral density (BMDt) and cortical with subcortical bone mineral density (BMDsc)] and the architectural parameters [cortical bone area (CBA), cortical thickness (C-th), moment of inertia (Im) and polar moment of inertia (Ip)] were measured in 115 healthy premenopausal women, 48 osteoporotic postmenopausal women and 78 age-matched healthy postmenopausal women. Age-matched healthy women had higher values of vBMD and architectural parameters at the distal radius than osteoporotic women. Premenopausal women had higher values of vBMD and architectural parameters at the distal radius than postmenopausal women. The differences in the architectural parameters between age-matched healthy women and osteoporotic women were more pronounced when only the high density area (threshold 0.70 cm(-1)) was included. However, the differences in architectural parameters between premenopausal women and postmenopausal women were significant using even the lowest threshold value of 0.50 cm(-1) in the calculation. Receiver operating characteristic (ROC) curves were constructed and the areas under the curves calculated to evaluate the discriminating power of vBMD and architectural parameters. Comparison of the different ROC curves showed no statistical significance. In conclusion, our results suggest that both the density and mass distribution of the radius were clearly different between the healthy women and osteoporotic women. The differences in architectural parameters were more useful for studying the pathophysiology of osteoporosis than for contributing to the diagnosis. Determination of the cross-sectional mass distribution of bone combined with BMD should offer more information than BMD alone in the study of the pathophysiology of osteoporosis.

Reduced bone mineral density in young adults following cure of acute lymphoblastic leukaemia in childhood.

Bone mineral density (BMD), serum osteocalcin and type I collagen C-telopeptide (ICTP) were assessed in a cohort of 31 (16 males) adults who had received cranial irradiation in childhood as part of their treatment for acute lymphoblastic leukaemia (ALL). Markers of bone turnover were compared with those of 35 age and body mass index (BMI) matched young adults (18 male). Growth hormone status had previously been determined using an insulin tolerance test and arginine stimulation test. Eight patients were classified as severe growth hormone deficiency (group 1), 12 patients as growth hormone insufficient (group 2) and 11 patients as normal (group 3). Vertebral trabecular BMD, lumbar spine and femoral neck integral BMD and forearm cortical bone mineral content (BMC) was measured 17.8 (6.8–28.6) years after cranial irradiation and was expressed as Z (standard deviation) scores. There was a significant reduction in vertebral trabecular BMD (median Z score –1.25, P < 0.001), in lumbar spine integral BMD (median Z score –0.74, P = 0.001), in forearm cortical BMC (median Z score –1.35, P < 0.001), and less so in femoral neck integral BMD (median Z score –0.43, P = 0.03). There was no difference among the growth hormone status groups for the following BMD measurements: vertebral trabecular BMD, lumbar spine integral BMD or femoral neck integral BMD (P = 0.8, P = 0.96 and P = 0.4 respectively). There was only a marginal significant difference for BMD at the wrist between growth hormone status groups (P = 0.04). There was no correlation between the BMD measurements with time since or age at diagnosis and no difference in markers of bone turnover between patients and controls; median serum osteocalcin 13.3 and 12.0 ng ml (P = 0.7), respectively, and for ICTP 5.0 and 4.9 μg L (P = 0.67) respectively. In conclusion, there is a highly significant reduction in BMD in young adults following treatment for ALL in childhood. The reduction in BMD affects both trabecular and cortical bone but did not seem to be related to time since diagnosis, age at diagnosis, or current growth hormone status. Possible explanations include a direct effect of chemotherapy, steroids or both on bone during childhood and hence an effect on the accretion of bone mass. In view of the risk of fractures in patients with osteopenia, adults treated for ALL in childhood may be at an increased risk of bone fractures later in life irrespective of the underlying cause of the osteopenia and thus intervention should be considered. © 1999 Cancer Research Campaign

Assessment of vertebral bone mineral density using volumetric quantitative CT.

The purpose of this work was to determine the precision and diagnostic efficacy of bone mineral density (BMD) measures based on volumetric quantitative CT (QCT) of the spine. Volumetric CT scans of L1 and L2 (GE-9800Q; 80 kVp, 140 mAs, 3 mm slices) were acquired in a cohort of 62 osteoporotic women (mean age 70.4 years, T(DXA hip or spine) < -2.5), of whom 20 had vertebral fractures and 42 were nonfractured control subjects. An image analysis technique delineated trabecular, cortical, and integral regions in reference to a vertebra-fixed coordinate system. We computed precision values and fracture control differences for these new regions and for single-slice QCT and dual X-ray absorptiometry (DXA) measures synthesized from the volumetric data. Volumetric trabecular BMD showed higher precision (1.3%) than the synthesized single-slice measures (2.1-2.8%). Volumetric and single-slice trabecular BMD showed equivalent decrements between fractured and nonfractured subjects (17-19%), with integral BMD showing smaller and less significant differences (7-8%). Volumetric and single-slice QCT techniques are equivalent for vertebral fracture risk estimation, but volumetric techniques should be superior for monitoring therapy efficacy.

Trochanteric hip fracture: strong association with spinal trabecular bone mineral density measured with quantitative CT.

To determine the discriminatory capability for hip fracture of trabecular and integral bone mineral density (BMD) measured with quantitative computed tomography (CT) of the spine. Fifty-six women who had sustained hip fractures and 59 control subjects underwent volumetric quantitative CT of L1 and L2 and dual x-ray absorptiometry of the hip. BMD was measured in vertebral regions of interest that encompassed trabecular, cortical, and integral bone. Logistic regression analysis was applied to each BMD measure to derive age-, weight-, and height-adjusted relative risk (RR) factors for overall hip fracture and for trochanteric fracture and cervical fracture separately. Spinal trabecular BMD was modestly related to overall hip fracture (RR, 1.4-1.7; P < .05) and strongly associated with trochanteric fracture (RR, 4.2-4.5; P < .005). Spinal integral BMD related similarly to overall hip fracture (RR, 1.7-1.8; P < .05) but more weakly to trochanteric fracture (RR, 2.3-3.2; P < .01). No spinal BMD measures were significantly related to cervical fracture. BMD at the hip was strongly related to overall hip fracture (RR, 3.3-4.3; P < .001), cervical fracture (RR, 2.7-5.3; P < .001), and trochanteric fracture (RR, 2.9-7.2; P < .001). Spinal trabecular BMD is strongly associated with both trochanteric and vertebral fractures.

Volumetric quantitative computed tomography of the proximal femur: Precision and relation to bone strength

We have developed a three-dimensional computed tomography (CT) scanning and image analysis method for measurement of trabecular and integral bone mineral density (BMD) and geometry in automatically determined femoral-neck and trochanteric subregions of the proximal femur. We measured the correlation of the density and geometry variables to femoral strength assessed in vitro under loading simulating a single-limb condition and a fall to the side. While BMD alone accounted for 48%–77% of the variability in strength for the stance loading configuration, femoral neck cross-sectional area (minCSA) and femoral neck axis length (FNAL) also contributed independently to femoral strength, and a combination of BMD and geometry variables explained 87%–93% of the variance in the data. For the fall loading configuration, trochanteric trabecular BMD alone explained 87% of the variability of strength. The reproducibility in vivo of the technique was assessed in a group of seven postmenopausal women, who underwent repeat scans with repositioning. For trabecular BMD, the precision was 1.1% and 0.6% for the femoral neck and trochanteric subregions, respectively, compared to 3.3% and 1.6% for the corresponding integral envelopes. Thus, trabecular BMD measurements were reproducible and highly correlated to biomechanical strength measurements. These results support further exploration of quantitative CT for assessment of osteoporosis at the proximal femur.