In Vivo Magnetic Resonance Detects Rapid Remodeling Changes in the Topology of the Trabecular Bone Network After Menopause and the Protective Effect of Estradiol

Laboratory for Structural NMR Imaging, Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research (Impact Factor: 6.83). 05/2008; 23(5):730-40. DOI: 10.1359/jbmr.080108
Source: PubMed


Estrogen depletion after menopause is accompanied by bone loss and architectural deterioration of trabecular bone. The hypothesis underlying this work is that the microMRI-based virtual bone biopsy can capture the temporal changes of scale and topology of the trabecular network and that estrogen supplementation preserves the integrity of the trabecular network.
Subjects studied were early postmenopausal women, 45-55 yr of age (N = 65), of whom 32 were on estrogen (estradiol group), and the remainder were not (control group). Early menopause was defined by amenorrhea for 6-24 mo and elevated serum follicle-stimulating hormone (FSH) concentration. The subjects were evaluated with three imaging modalities at baseline and 12 and 24 mo to determine the temporal changes in trabecular and cortical architecture and density. microMRI of the distal radius and tibia was performed at 137 x 137 x 410-microm(3) voxel size. The resulting bone volume fraction maps were Fourier interpolated to a final voxel size of 45.7 x 45.7 x 136.7 microm(3), binarized, skeletonized, and subjected to 3D digital topological analysis (DTA). Skeletonization converts trabecular rods to curves and plates to surfaces. Parameters quantifying scale included BV/TV, whereas DTA parameters included the volume densities of curves (C) and surface (S)-type voxels, as well as composite parameters: the surface/curve ratio (S/C), and erosion index (EI, ratio of the sum of parameters expected to increase with osteoclastic resorption divided by the sum of those expected to decrease). For comparison, pQCT of the same peripheral locations was conducted, and trabecular density and cortical structural parameters were measured. Areal BMD of the lumbar vertebrae and hip was also measured.
Substantial changes in trabecular architecture of the distal tibia, in particular as they relate to topology of the network, were detected after 12 mo in the control group. S/C decreased 5.6% (p < 0.0005), and EI increased 7.1% (p < 0.0005). Most curve- and profile-type voxels (representative of trabecular struts), increased significantly (p < 0.001). Curve and profile edges resulting from disconnection of rod-like trabeculae increased by 9.8% and 5.1% (p = 0.0001 and <0.001, respectively). Similarly, DXA BMD in the spine and hip decreased 2.6% and 1.3% (p < 0.0001 and <0.005, respectively), and pQCT cortical area decreased 3.6% (p = 0.0001). However, neither trabecular density nor BV/TV changed. Furthermore, none of the parameters measured in the estradiol group were significantly different after 12 mo. Substantial differences in the mean changes from baseline between the estradiol treatment and control groups, in particular after 24 mo, were observed, with relative group differences as large as 13% (S/C, p = 0.005), and the relative changes in the two groups had the opposite sign for most parameters. The observed temporal alterations in architecture are consistent with remodeling changes that involve gradual conversion of plate-like to rod-like trabecular bone along with disconnection of trabecular elements, even in the absence of a net loss of trabecular bone. The high-resolution 3D rendered images provide direct evidence of the above remodeling changes in individual subjects. The radius structural data indicated similar trends but offered no definitive conclusions.
The short-term temporal changes in trabecular architecture after menopause, and the protective effects of estradiol ensuring maintenance of a more plate-like TB architecture, reported here, have not previously been observed in vivo. This work suggests that MRI-based in vivo micromorphometry of trabecular bone has promise as a tool for monitoring osteoporosis treatment.

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Available from: Babette Zemel, Jul 21, 2014
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    • "In postmenopausal women with type 2 diabetes, we demonstrated that there are larger trabecular bone holes at the distal radius compared to women without diabetes [12], and others have reported that cortical bone is more porous in those with diabetes [13]. Trabecular bone microarchitecture can be modified by osteoporosis treatments [14-16], yet whether there is skeletal response to antiresorptive medication in individuals with diabetes is controversial [17,18]. "
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    ABSTRACT: Background The risk of experiencing an osteoporotic fracture is greater for adults with type 2 diabetes despite higher than normal bone mineral density (BMD). In addition to BMD, trabecular bone microarchitecture contributes to bone strength, but is not assessed using conventional BMD measurement by dual x-ray absorptiometry (DXA). The aim of this study was to compare two year changes in trabecular bone microarchitecture in women with and without type 2 diabetes. Methods We used a 1 Tesla magnetic resonance imaging (MRI) scanner to acquire axial images (resolution 195 μm × 195 μm × 1000 μm) of the distal radius. We report the change in the number and size of trabecular bone holes, bone volume fraction (BVTV), trabecular thickness (Tb.Th), number (Tb.N) and separation (Tb.Sp), endosteal area, nodal and branch density for each group. Lumbar spine and proximal femur BMD were measured with DXA (Hologic, Discovery QDR4500A) at baseline and follow-up. Using a multivariable linear regression model, we evaluated whether the percent change in the trabecular bone microarchitecture variables differed between women with and without type 2 diabetes. Results Of the 54 participants at baseline with valid MRI image sets, 37 participants (baseline mean [SD] age, 70.8 [4.4] years) returned for follow-up assessment after 25.4 [1.9] months. Lumbar spine BMD was greater for women with diabetes compared to without diabetes at both baseline and follow-up. After adjustment for ethnicity, women with diabetes had a higher percent increase in number of trabecular bone holes compared to controls (10[1] % versus −7 [2]%, p=0.010), however results were no longer significant after adjustment for multiple comparisons (p=0.090). There were no differences in the change in other trabecular bone microarchitecture variables between groups. Conclusion There were no differences in percent change in trabecular bone microarchitecture variables over two years in women with type 2 diabetes compared to women without diabetes. This study provides feasibility data, which will inform future trials assessing change in trabecular bone microarchitecture in women with type 2 diabetes. Larger studies using higher resolution imaging modalities that can assess change in trabecular and cortical bone compartments in women with type 2 diabetes are needed.
    BMC Musculoskeletal Disorders 03/2013; 14(1):114. DOI:10.1186/1471-2474-14-114 · 1.72 Impact Factor
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    • "and topological aspects [39]. "
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    ABSTRACT: High-resolution peripheral quantitative computed tomography (HR-pQCT) is an in-vivo technique used to analyze the distal radius and tibia. It provides a voxel size of 82μm. In addition to providing the usual microarchitecture parameters, local topological analysis (LTA) depicting rod- and plate-like trabeculae may improve prediction of bone fragility. Thirty-three women with prevalent wrist fractures from the OFELY cohort were compared with age-matched controls. Bone microarchitecture, including the structural model index (SMI), was assessed by HR-pQCT, and micro-finite element analysis (μFE) was computed on trabecular bone images of the distal radius (XtremeCT, Scanco Medical AG). A new LTA method was applied to label each bone voxel as a rod, plate or node. Then the bone volume fraction (BV/TV*), the rod, plate and node ratios over bone volume (RV/BV*, PV/BV*, NV/BV*) or total volume (RV/TV*, PV/TV*, NV/TV*) and the rod to plate ratio (RV/PV*) were calculated. Associations between LTA parameters and wrist fractures were computed in a conditional logistic regression model. Multivariate models were tested to predict the μFE-derived trabecular bone stiffness. RV/TV* (OR=4.41 [1.05-18.62]) and BV/TV* (OR=6.45 [1.06-39.3]), were significantly associated with prevalent wrist fracture, after adjustment for ultra distal radius aBMD. Multivariate linear models including PV/TV* or BV/TV*+RV/PV* predicted trabecular stiffness with the same magnitude as those including SMI. Conversion from plates into rods was significantly associated with bone fragility, with a negative correlation between RV/PV* and trabecular bone stiffness (r=-0.63, p<0.0001). We conclude that our local topological analysis is feasible for a voxel size of 82μm. After further validation, it may improve bone fragility description.
    Bone 06/2012; 51(3):362-8. DOI:10.1016/j.bone.2012.06.008 · 3.97 Impact Factor
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    • "Saha et al. developed digital topological analysis (DTA) [10] [11]which classifies surfaces (plates), curves (rods), junctions, and edges in a skeletal representation of a TB network using local topological parameters [10] [12] [13]. Although DTA is widely applied [5] [6] [14] [15], a major limitation of the method is that resulting classifications are inherently discrete failing to distinguish between narrow and wide plates. Later, Saha et al. developed volumetric topological analysis algorithm (VTA) [16] characterizing the topology of individual trabeculae on the continuum between a perfect plate and a perfect rod. "
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    ABSTRACT: Osteoporosis, characterized by low bone mineral density (BMD) and micro-architectural deterioration of trabecular bone (TB), increases risk of fractures associated with substantial morbidity, mortality, and financial costs. A quantitative measure of TB micro-architecture with high reproducibility, large between-subjects variability and strong association with bone strength that may be computed via in vivo imaging would be an important indicator of bone quality for clinical trials evaluating fracture risks under different clinical conditions. Previously, the notion of tensor scale (t-scale) was introduced using an ellipsoidal model that yields a unified representation of structure size, orientation and anisotropy. Here, we develop a new 3-D t-scale algorithm for fuzzy objects and investigate its application to compute quantitative measures characterizing TB micro-architecture acquired by in vivo multi-row detector CT (MD-CT) imaging. Specifically, new measures characterizing individual trabeculae on the continuum of a perfect plate and a perfect rod and their orientation are directly computed in a volumetric BMD representation of a TB network. Reproducibility of these measures is evaluated using repeat MD-CT scans and also by comparing their correlation between MD-CT and micro-CT imaging. Experimental results have demonstrated that the t-scale-based TB micro-architectural measures are highly reproducible with strong association of their values at MD-CT and micro-CT resolutions. Results of an experimental mechanical study have proved these measures' ability to predict TB's bone strength.
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