Longitudinal Assessment of In Vivo Bone Dynamics in a Mouse Tail Model of Postmenopausal Osteoporosis

Abstract

Recently, it has been shown that transient bone biology can be observed in vivo using time-lapse microcomputed tomography (lCT) in the mouse tail bone. Nevertheless, in order for the mouse tail bone to be a model for human disease, the hallmarks of any disease must be mimicked. The aim of this study was to investigate whether postmenopausal osteoporosis could be modeled in caudal vertebrae of C57Bl/6 mice, considering static and dynamic bone morphometry as well as mechanical properties, and to describe temporal changes in bone remodeling rates. Twenty C57Bl/6 mice were ovariectomized (OVX, n = 11) or sham-operated (SHM, n = 9) and monitored with in vivo lCT on the day of surgery and every 2 weeks after, up to 12 weeks. There was a significant decrease in bone volume fraction for OVX (-35%) compared to SHM (?16%) in trabecular bone (P \ 0.001). For OVX, highturnover bone loss was observed, with the bone resorption rate exceeding the bone formation rate (P \ 0.001). Furthermore there was a significant decrease in whole-bone stiffness for OVX (-16%) compared to SHM (?11%, P \ 0.001). From these results we conclude that the mouse tail vertebra mimics postmenopausal bone loss with respect to these parameters and therefore might be a suitable model for postmenopausal osteoporosis. When evaluating temporal changes in remodeling rates, we found that OVX caused an immediate increase in bone resorption rate (P \ 0.001) and a delayed increase in bone formation rate (P \ 0.001). Monitoring transient bone biology is a promising method for future research.

Minimizing Interpolation Bias and Precision Error in In Vivo µCT-Based Measurements of Bone Structure and Dynamics

“…Even in rats with lower rates of bone remodeling, the level of noise quantified in the current study remains significantly lower than previously measured differences in remodeling due to osteoporosis or drug treatment 1, 12 . Combined with previous studies by other groups 3, 16, 18, 21, 23 , this indicates that the in vivo dynamic bone histomorphometry technique has adequate precision to detect physiologically relevant changes in bone remodeling. In vivo dynamic bone histomorphometry has many strengths, including its ability to provide noninvasive, longitudinal measures.…”

“…In addition to tracking changes in the trabecular microstructure, several recent studies have developed in vivo dynamic bone histomorphometry techniques that utilize registered μCT images to identify regions of bone formation and resorption, allowing for longitudinal assessment of bone remodeling and structural changes in the caudal vertebra 16, 21, 23 and at the proximal tibia 3, 12 . In these studies, animals are scanned at multiple time-points, and the resulting μCT images are registered, thresholded, and subtracted to identify, on a voxel-by-voxel basis, locations where bone has formed or resorbed 3, 12, 21 .…”

Males have Inferior Achilles Tendon Material Properties Compared to Females in a Rodent Model

“…Previous studies in female rats demonstrated significant alterations in bone morphology and muscle mass as early as two and four weeks, respectively, following ovariectomy 6, 13 .…”

μCT-based, in vivo dynamic bone histomorphometry allows 3D evaluation of the early responses of bone resorption and formation to PTH and alendronate combination therapy

“…Resorption is identified as the bone areas only present in the earlier images, while bone formation is identified as the bone areas only present in the later scans. This technique provides accurate quantification of bone remodeling in mouse caudal vertebrae in models of post-menopausal osteoporosis [29] and mechanical loading [28, 30, 31]. …”