Longitudinal evaluation of the effects of alendronate on MRI bone microarchitecture in postmenopausal osteopenic women

Abstract

We evaluated longitudinal effects of alendronate on MRI-based trabecular bone structure parameters derived from dual thresholding and fuzzy clustering (BE-FCM) trabecular bone segmentation. Treatment effects were observed in the distal tibia after 24 months. The BE-FCM method increased correlations to HR-pQCT-based parameters.

Introduction: High-resolution magnetic resonance imaging (MRI) allows for non-invasive bone microarchitecture analysis. The goal of this study was to examine the potential of MRI-based trabecular bone structure parameters to monitor effects of alendronate in humans in vivo, and to compare the results to HR-pQCT and DXA measurements.

Materials and methods: Postmenopausal osteopenic women were divided into alendronate treatment and control groups, and imaged at baseline, 12 months, and 24 months (n = 52 at baseline) using 3T MRI, HR-pQCT, and DXA. Image acquisition sites included distal tibia (MRI and HR-pQCT), distal radius (MRI, DXA, and HR-pQCT), and the proximal femur (MRI and DXA). Two different regions of interest were evaluated. One contained the trabecular bone region within the entire MRI acquisition, and the second contained a subregion matched to the region contained in the HR-pQCT acquisition. The trabecular bone was segmented using two different methods; dual thresholding and BE-FCM. Trabecular bone structure parameters included bone volume fraction (BV/TV), number (Tb.N), spacing (Tb.Sp), and thickness (Tb.Th), along with seven geodesic topological analysis (GTA) parameters. Longitudinal changes and correlations to HR-pQCT and DXA measurements were evaluated.

Results: Apparent Tb.N and four GTA parameters showed treatment effects (p < 0.05) in the distal tibia after 24 months in the entire MRI region using BE-FCM, as well as Tb.N using dual thresholding. No treatment effects after 24 months were observed in the HR-pQCT or in MRI analysis for the HR-pQCT-matched regions. Apparent BV/TV and Tb.N from BE-FCM had significantly higher correlations to HR-pQCT values compared to those derived from thresholding.

Conclusions: This study demonstrates the influence of computational methods and region of interest definitions on measurements of trabecular bone structure, and the feasibility of MRI-based quantification of longitudinal changes in bone microarchitecture due to bisphosphonate therapy. The results suggest that there may be a need to reevaluate the current standard HR-pQCT region definition for increased treatment sensitivity.

Fig. 1

The number of subjects in the treatment and control groups at baseline, 12, and 24 months. The top three numbers represent the number of subjects that have completed distal radius (R), distal tibia (T), and proximal femur (F) MRI scans with sufficient image quality for further analysis, respectively. The number in parentheses represents the number of subjects scanned using HR-pQCT, while the lower number of completed MRI scans are due to incomplete scans because of patient discomfort, or inadequate image quality due to patient motion during the scan.

Fig. 2

To the left: an example DXA image of the radius with ultra-distal (UD) and total (largest rectangle) regions marked. To the right: the MRI view of the same radius with the MRI scan ROI (red) and the HR-pQCT-matched ROI (blue).

Fig. 3

To the left: example images of the tibia, and to the right: example images of the radius. From top to bottom: a slice from an MR image, the corresponding slice from registered HR-pQCT image, and the registered HR-pQCT image (green) overlaid on the MR image.

Fig. 4

An example slice from a proximal femur MRI scan. a) the slice field of view. b) Image centered around the trochanter with the ROI delineated in red. c) Trabecular bone segmentation using dual thresholding. d) Trabecular bone segmentation using BE-FCM after thresholding. e) Trabecular bone segmentation using BE-FCM.

Fig. 5

Example trabecular bone in a slice from an MRI image of a subject with higher GTA parameter values than average (left), and lower than average (right). Pixels belonging to the same junction have the same color. The color encodes the volume a junction is supporting, with red (blue) signifying high (low) apparent Tb.VJ.

Fig. 6

An example slice from a distal radius HR-pQCT scan. Left: the field of view of one slice with the ROI delineated in red. Right: trabecular bone segmentation using thresholding.

Fig. 7

Longitudinal results of BE-FCM-based structure parameters from MRI using the entire MRI ROIs. Percent change (mean and SE) from baseline after 12 and 24 months for the distal radius, distal tibia, and proximal femur (after 12 months) are displayed, along with group difference for the treatment (T) and control (C) groups. Tb.JO was left out due to very large variations in the data.

Fig. 8

Longitudinal results of BE-FCM-based structure parameters from MRI using HR-pQCT-matched ROIs. Percent change (mean and SE) from baseline after 12 and 24 months in the MRI data for the distal radius, and distal tibia, along with group differences for the treatment (T) and control (C) groups. Tb.JO was left out due to very large variations in the data.

Fig. 9

Correlations between structure parameters from MR and HR-pQCT computed using dual thresholding (t) and BE-FCM (f) trabecular bone segmentation. All correlations were statistically significant (p<0.0001).