ABSTRACT:We evaluated the effect of testosterone treatment on trabecular architecture by µMRI in 10 untreated severely hypogonadal men. After 2 years, µMRI 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 (MRI) of the distal tibia and by DXA of the spine and hip. The MRI 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 ‫ס‬ 0.008). Architectural parameters assessed by MRI also changed: the surface-to-curve ratio increased 11% (p ‫ס‬ 0.004) and the topological erosion index decreased 7.5% (p ‫ס‬ 0.004). Conclusions: These results suggest the possibility that testosterone replacement of hypogonadal men improves trabecular architecture.

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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.

ABSTRACT:Introduction: Estrogen depletion after menopause is accompanied by bone loss and architectural deterioration of trabecular bone. The hypothesis underlying this work is that the MRI-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. Materials and Methods: Subjects studied were early postmenopausal women, 45-55 yr of age (N ‫ס‬ 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. MRI of the distal radius and tibia was performed at 137 × 137 × 410-m 3 voxel size. The resulting bone volume fraction maps were Fourier interpolated to a final voxel size of 45.7 × 45.7 × 136.7 m 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. Results: 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 ‫ס‬ 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 ‫ס‬ 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 ‫ס‬ 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-...

Osteoporosis is a major public health problem in men. Hypogonadal men have decreased BMD and deteriorated trabecular bone architecture compared with eugonadal men. Testosterone treatment improves their BMD and trabecular structure. We tested the hypothesis that testosterone replacement in hypogonadal men would also improve their bone's mechanical properties. Ten untreated severely hypogonadal and 10 eugonadal men were selected. The hypogonadal men were treated with a testosterone gel for 24 mo to maintain their serum testosterone concentrations within the normal range. Each subject was assessed before and after 6, 12, and 24 mo of testosterone treatment by MRI of the distal tibia. A subvolume of each MR image was converted to a microfinite element (FE) model, and six analyses were performed, representing three compression and three shear tests. The anisotropic stiffness tensor was calculated, from which the orthotropic elastic material constants were derived. Changes in microarchitecture were also quantified using newly developed individual trabeculae segmentation (ITS)-based and standard morphological analyses. The accuracy of these techniques was examined with simulated MR images. Significant differences in four estimated anisotropic elastic material constants and most morphological parameters were detected between the eugonadal and hypogonadal men. No significant change in estimated elastic moduli and morphological parameters was detected in the eugonadal group over 24 mo. After 24 mo of treatment, significant increases in estimated elastic moduli E 22 (9.0%), E 33 (5.1%), G 23 (7.2%), and G 12 (9.4%) of hypogonadal men were detected. These increases were accompanied by significant increases in trabecular plate thickness. These results suggest that 24 mo of testosterone treatment of hypogonadal men improves estimated elastic moduli of tibial trabecular bone by increased trabecular plate thickness.