Effect of testosterone replacement on trabecular architecture in hypogonadal men.

UNLABELLED: We evaluated the effect of testosterone treatment on trabecular architecture by microMRI in 10 untreated severely hypogonadal men. After 2 years, microMRI parameters of trabecular connectivity improved significantly, suggesting the possibility that testosterone improves trabecular architecture. INTRODUCTION: Osteoporosis, characterized by low BMD and diminished bone quality, is a significant public health problem in men. Hypogonadal men have decreased BMD and deteriorated trabecular architecture compared with eugonadal men, and testosterone treatment improves their BMD. We tested the hypothesis that testosterone replacement in hypogonadal men would also improve their trabecular architecture. MATERIALS AND METHODS: We selected 10 untreated severely hypogonadal men and treated them with a testosterone gel for 24 months to maintain their serum testosterone concentrations within the normal range. Each subject was assessed before and after 6, 12, and 24 months of testosterone treatment by magnetic resonance microimaging (microMRI) of the distal tibia and by DXA of the spine and hip. The microMRI parameters reflect the integrity of the trabecular network and include the ratio of all surface voxels (representing plates) to curve voxels (representing rods) and the topological erosion index, a ratio of topological parameters expected to increase on trabecular deterioration to those expected to decrease. The higher the surface-to-curve ratio and the lower the topological erosion index, the more intact the trabecular network. RESULTS: Serum testosterone concentrations increased to midnormal after 3 months of treatment and remained normal thereafter. After 24 months of testosterone treatment, BMD of the spine increased 7.4% (p<0.001), and of the total hip increased 3.8% (p=0.008). Architectural parameters assessed by microMRI also changed: the surface-to-curve ratio increased 11% (p=0.004) and the topological erosion index decreased 7.5% (p=0.004). CONCLUSIONS: These results suggest the possibility that testosterone replacement of hypogonadal men improves trabecular architecture.

Method for cortical bone structural analysis from magnetic resonance images.

RATIONALE AND OBJECTIVES: Quantitative evaluation of cortical bone architecture as a means to assess bone strength typically is accomplished on the basis of images obtained by means of dual-energy X-ray absorptiometry (DXA) or computed tomography. Magnetic resonance (MR) imaging has potential advantages for this task in that it allows imaging in arbitrary scan planes at high spatial resolution. However, several hurdles have to be overcome to make this approach practical, including resolution of issues related to nonlinear receive coil sensitivity, variations in marrow composition, and the presence of periosteal isointense tissues, which all complicate segmentation. The aim of this study is to develop MR acquisition and analysis methods optimized for the detection of cortical boundaries in such complex geometries as the femoral neck. MATERIALS AND METHODS: Cortical boundary detection is achieved by radially tracing intensity profiles that intersect the periosteal and endosteal boundaries of bone. Profiles subsequently are normalized to the intensity of the marrow signal, processed with morphologic image operators, and binarized. The resulting boundaries are mapped back onto the spatial image, and erroneous boundary points are removed. From the detected cortical boundaries, cortical cross-sectional area and thickness are computed. The method was evaluated on cortical bone specimens and human volunteers on the basis of high-resolution images acquired at a 1.5-Tesla field strength. To assess whether the method is sensitive to detect the expected dependencies of cortical parameters in weight-bearing bone on overall habitus, 10 women aged 46-73 years (mean age, 56 years) underwent the cortical imaging protocol in the proximal femur, and results were compared with DXA bone mineral density parameters of the hip and spine. RESULTS: Reproducibility was approximately 2%. Double oblique images of the femoral neck in the 10 women studied showed that cortical cross-sectional area correlated strongly with height (r = 0.88; p = .0008), whereas cortical diameter versus age approached significance (r = 0.61; p = .06). Measurements in specimens of some cortical parameters indicated resolution dependence. However, note that specimen ranking within each parameter remained constant across all resolutions studied. CONCLUSION: Data suggest the new method to be robust and applicable on standard clinical MR scanners at arbitrary anatomic locations to yield clinically meaningful quantitative results.

Quantitative magnetic resonance imaging in the calcaneus and femur of women with varying degrees of osteopenia and vertebral deformity status.

Quantitative magnetic resonance imaging (QMRI) allows measurement of two parameters that are related to the integrity of the trabecular bone: R2*, the rate constant of the free induction signal, and trabecular bone volume fraction (BVF), the counterpart of apparent density. In this work, R2* and BVF were measured in 68 women (mean age, 58.2 +/- 9.5 years) of varying spinal bone mineral density (BMD) T scores (mean, -1.37 +/- 1.54) and vertebral fracture status on a commercial 1.5 T whole-body imager using customized image acquisition and processing techniques. Twenty-five of the patients had vertebral fractures, characterized by the total cumulative deformity burden exceeding 200%. R2* was measured in the calcaneus and proximal femur and BVF could be measured in the calcaneus only. On a pixel-by-pixel basis, calcaneal R2* and BVF within each subject were highly positively correlated (r2 = 0.61 +/- 0.11) but the correlation of region-of-interest (ROI) means for different calcaneal sites among patients was weaker (r2 = 0.34; p < 0.0001). The strongest discriminator of vertebral deformity was R2* of the calcaneus, which was lower in the fracture group, consistent with lower trabecular density. Among the calcaneal sites examined, the subtalar region, a location characterized by dense nearly horizontal trabeculae that transmit the stresses imparted by body weight from the tibia to the heel, best discriminated the two groups (p = 0.0001), with 77% diagnostic accuracy as determined from the area under the receiver operating characteristic (ROC) curve (compared with 66% for vertebral BMD). The cavum calcanei, an anterior site of low trabecular density, and the tuber calcanei (the location ordinarily used for ultrasound measurements) also had significantly reduced R2* in the fracture group (p < 0.005 and p = 0.01, respectively). The R2av*, computed as the average of all pixels in the calcaneus, was a strong discriminator as well (p < 0.005). On the other hand, calcaneal BVF was only marginally discriminating (p = 0.05). Among the BMD sites examined, the lumbar spine (average L1-L4) was significant (p = 0.005, 66% diagnostic accuracy), as was the femoral neck (p = 0.01). The data suggest the calcaneus to be suited as a surrogate site to assess vertebral osteoporosis and that R2* is sensitive to alterations in bone quality not captured by density.

Deterioration of trabecular architecture in hypogonadal men.

Bone strength depends on trabecular architecture, characterized by interconnected plates and rods. In osteoporosis, the plates become fenestrated, resulting in more rods that deteriorate and become disconnected. In men, hypogonadism is a common cause of osteoporosis. To determine whether male hypogonadism affects trabecular architecture, we selected 10 men with severe, untreated hypogonadism, and for each hypogonadal man, we selected a eugonadal man matched for race and age. Trabecular architecture in the distal tibia was assessed by magnetic resonance microimaging. Two composite topological indices were determined: the ratio of surface voxels (representing plates) to curve voxels (representing rods), which is higher when architecture is more intact; and the erosion index, a ratio of parameters expected to increase upon architectural deterioration to those expected to decrease, which is higher when deterioration is greater. The surface/curve ratio was 36% lower (P = 0.004), and the erosion index was 36% higher (P = 0.003) in the hypogonadal men than in the eugonadal men. In contrast, bone mineral density of the spine and hip were not significantly different between the two groups. We conclude that male hypogonadism is associated with marked deterioration of trabecular architecture and to a greater degree than bone densitometry of the spine and hip suggests.

Topology-based orientation analysis of trabecular bone networks.

After bone mineral density, orientation is the major determinant of trabecular bone strength and is thus of significant interest in understanding the clinical implications of osteoporotic bone loss. The methods used to measure orientation and anisotropy of the trabecular bone have largely relied on deriving global measures along test lines, computing the best-fit ellipsoid, and decomposing to eigenvalue-eigenvector pairs that yield the mean orientation and anisotropy of the region. These techniques ignore the differences between measuring the orientation of trabecular plates versus rods, and do not provide insight into the relationship between local orientation and biomechanical stresses. Digital topological analysis allows a unique determination of each voxel's topological class as belonging to a plate, rod, or junction. The digital topology-based orientation analysis (DTA-O) method extracts the voxels belonging to plates and determines the local surface normal by fitting a plane through the local neighborhood BVF map. Modeling regional distributions of these vectors allows assessment of anisotropy measures, such as mean and variance of the orientation distribution. High-resolution microcomputed tomography, synthetic, and in vivo images were used for a validation of the new method and compare the results with the mean intercept length (MIL) technique. The results indicate that DTA-O is a better measure of trabecular orientation and anisotropy than MIL. Applying DTA-O to a recently completed study on the distal radius of 82 subjects [F.W. Wehrli et al., J. Bone Min. Res. 16, 1520 (2001)] shows that the mean orientation and anisotropy at the medial and lateral sides in the distal radius mataphyseal trabecular network are consistent with the mechanical stresses acting on the radius during common tasks.

Role of magnetic resonance for assessing structure and function of trabecular bone.

The strength of trabecular bone and its resistance to fracture traditionally have been associated with apparent density. This paradigm assumes that neither the ultrastructural nor microstructural make-up of the bone is altered during aging and osteoporosis. During the past decade there has been growing evidence from both laboratory and clinical studies against this view. Recent advances in noninvasive imaging technology, notably micro-magnetic resonance imaging (micro MRI) and computed tomography, offer an opportunity to test the hypothesis that architecture is an independent contributor to bone strength. MRI appears to be ideally suited for this task because bone marrow has uniform high signal intensity while bone appears with background intensity, thus yielding a binary system tomographic system. However, in vivo trabecular bone imaging is hampered by the limited signal-to-noise ratio that precludes voxel sizes much smaller than trabecular thickness, which would be required to yield a bimodal intensity histogram for segmentation of the image into bone and marrow. The resulting partial volume blurring leads to fuzzy boundaries. Successful structure analysis thus demands more elaborate processing strategies. This article reviews new approaches conceived in the authors' laboratory toward acquisition, processing, and structural analysis of trabecular bone images in the limited spatial resolution regimen of in vivo micro MRI. These methods are shown to provide detailed insight into the three-dimensional trabecular network topology and scale at the distal radius or distal tibia that typically serve as surrogate sites. The micro MRI-derived structural parameters are shown to be associated with the bone's biomechanical properties and fracture resistance. Further, the technology has advanced to a stage permitting serial studies in laboratory animals and humans as a means to evaluate the effects of treatment. The method currently is confined to peripheral skeletal sites, and its extension to typical fracture sites such as the proximal femur hinges on further advances in detection sensitivity.

Changes in trabecular microarchitecture in postmenopausal women on bisphosphonate therapy.

PURPOSE: In addition to bone mineral density (BMD), trabecular microstructure contributes to skeletal strength. Our goal was to examine changes in trabecular microstructure in women on therapy. MATERIALS AND METHODS: We followed 10 postmenopausal women receiving a bisphosphonate, risedronate (35 mg once weekly), over 12 months and examined trabecular microarchitecture with high resolution wrist MR images (hr-MRI). MRI parameters included bone volume/total volume (BV/TV), surface density (representing plates), curve density (representing rods), surface-to-curve ratio and erosion index (depicting deterioration). We assessed BMD of the spine, hip and radius and markers of bone turnover. RESULTS: Women had been receiving bisphosphonate therapy for 43+/-9 months (mean+/-SD) prior to the first MRI. Indices of hr-MRI demonstrated improvement in surface-to-curve ratio (13.0%) and a decrease in erosion index (12.1%) consistent with less deterioration (both p<0.05). BMD of the spine, hip and radius and markers of bone turnover remained stable. Parameters of hr-MRI were associated with 1/3 distal radius BMD (correlation coefficient 0.71 to 0.86, p<0.05). DISCUSSION: We conclude that hr-MRI of the radius demonstrates improvements in trabecular microstructure not appreciated by conventional BMD and provides additional information on parameters that contribute to structural integrity in patients on antiresorptive therapy.

Quantitative high-resolution magnetic resonance imaging reveals structural implications of renal osteodystrophy on trabecular and cortical bone.

PURPOSE: To explore the potential role of micro-magnetic resonance imaging (micro-MRI) for quantifying trabecular and cortical bone structural parameters in renal osteodystrophy (ROD), a multifactorial disorder of bone metabolism, traditionally evaluated by bone biopsy. MATERIALS AND METHODS: Seventeen hemodialysis patients (average PTH level = 502 +/- 415 microg/liter) were compared with 17 age-, gender-, and body mass index (BMI)-matched control subjects. The average dialysis duration for the patients was 5.5 years (range = 0.96-18.2 years). Three-dimensional (3D) fast large-angle spin-echo (FLASE) MR images of the distal tibia (voxel size = 137 x 137 x 410 microm(3)) were processed to yield bone volume fraction (BV/TV). From a skeletonized representation of the trabecular bone network, the topology of each bone voxel was determined providing surface and curve voxel densities (SURF and CURV) and the topological erosion index (EI). Further, high-resolution two-dimensional (2D) spin-echo images were collected at the tibial midshaft for measurement of cortical bone cross-sectional area (CCA), relative CCA expressed as a percentage of total bone area (RCA), and mean cortical thickness (MCT). RESULTS: The data show both RCA and MCT to be lower in the patients (61.2 vs. 69.1%, P = 0.008, and 4.53 vs. 5.19 mm, P = 0.01). BV/TV and SURF were lower, while EI was increased in the patients, although these differences were not quite significant (P = 0.06-0.09). All of the cortical and trabecular findings are consistent with increased bone fragility. CONCLUSION: The data suggest that micro-MRI may have potential to characterize the structural implications of metabolic bone disease, potentially providing a noninvasive tool for the evaluation of therapies for ROD.