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

Abstract

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-...

Commentary: Deciphering the link between architecture and biological response of a bone graft substitute

“…Unfortunately, the tools that can be used to study the in vivo evolution of the scaffold are too limited at present, so the assessment of the in vivo performance is generally performed a posteriori. ever, there is a clear trend towards this goal, and first in vitro and in vivo results have been reported [35,36].…”

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“…The treatment group showed improved trabecular structure compared to the placebo group but no significant change in BMD was detected. Topological changes of the trabecular bone network after menopause and the protective effect of estradiol were recently reported [275]. Estrogen depletion after menopause is accompanied by bone loss and architectural deterioration of trabecular bone.…”

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“…However, MRI-derived micro-architectural parameters detected a positive response to osteoporosis treatment [107][108][109]. Specifically, radial Tb.N and Tb.Sp significantly increased after 12 months of onceweekly parathyroid hormone treatment [109].…”