Quantification of skeletal growth, modeling, and remodeling by in vivo micro computed tomography

Abstract

In this study we established an image analysis scheme for the investigation of cortical and trabecular bone development during skeletal growth and tested this concept on in vivo µCT images of rats. To evaluate its efficacy, we applied the technique to young (1-month-old) and adult (3-month-old) rat tibiae with vehicle (Veh) or intermittent parathyroid hormone (PTH) treatment. By overlaying 2 sequential scans based on their distinct trabecular microarchitecure, we calculated the linear growth rate of young rats to be 0.31 mm/day at the proximal tibia. Due to rapid growth (3.7 mm in 12 days), the scanned bone region at day 12 had no overlap with the bone tissue scanned at day 0. Instead, the imaged bone region at day 12 represented newly generated bone tissue from the growth plate. The new bone of the PTH-treated rats had significantly greater trabecular bone volume fraction, number, and thickness than those of the Veh-treated rats, indicating PTH’s anabolic effect on bone modeling. In contrast, the effect of PTH on adult rat trabecular bone was found to be caused by PTH’s anabolic effect on bone remodeling. The cortical bone at the proximal tibia of young rats also thickened more in the PTH group (23%) than the Veh group (14%). This was primarily driven by endosteal bone formation and coalescence of trabecular bone into the cortex. This process can be visualized by aligning the local bone structural changes using image registration. As a result, the cortex after PTH treatment was 31% less porous, and had a 22% greater polar moment of inertia compared to the Veh group. Lastly, we monitored the longitudinal bone growth in adult rats by measuring the distance of bone flow away from the proximal tibial growth plate from 3 months to 19 months of age and discovered a total of 3.5 mm growth in 16 months. It was demonstrated that this image analysis scheme can efficiently evaluate bone growth, bone modeling, and bone remodeling, and is ready to be translated into a clinical imaging platform.

Astragalus Extract Mixture HT042 Improves Bone Growth, Mass, and Microarchitecture in Prepubertal Female Rats: A Microcomputed Tomographic Study

“…The tibial growth rate in the control group was 372.2 and 228.0  μ m/day during the first and second weeks, respectively, which corresponded with the previous observation [18, 19]. HT042 was shown to increase the tibial growth rate, which confirmed our previous studies on linear bone growth [13, 14].…”

“…During growth, the accumulation of trabecular bone mass in the metaphyseal region mostly results from longitudinal bone growth [19]. Chondrocytes within growth plate cartilage contribute to longitudinal bone growth through a combination of proliferation, cartilage matrix synthesis, and hypertrophy [20].…”

Postnatal development of the largest subterranean mammal (Bathyergus suillus): Morphology, osteogenesis, and modularity of the appendicular skeleton

“…The cortical bone of juvenile mammals is generally composed of woven bone and/or fibrolamellar bone . The higher proportion of vascularized areas, as well as high bone turnover resulting from metaphyseal relocation during early ontogeny result in increased endosteal and intracortical porosity of the diaphysis, which contribute to decreased bone strength of young bone . The ossified matrix of these tissues also have lower biomechanical properties as compared to lamellar or secondary bone tissues developed later in ontogeny .…”

PTH(1-34) and zoledronic acid have differing longitudinal effects on juvenile mouse femur strength and morphology

“…29 Anabolic effects of PTH treatment have also been demonstrated in the proximal tibia of juvenile rats. 30 While limited changes in response to PTH treatment were seen in our study of juvenile mouse femurs, this may be because the actively growing juvenile mouse is already at peak anabolic function, resulting in a ceiling effect, essentially preventing any additional anabolic effects to be seen from the addition of exogenous agents. However, the positive effects of PTH delivery in a juvenile animal model could potentially occur if bone modeling were attenuated by metabolic bone diseases, chronic disease, immobilization, or following radiotherapy or chemotherapy.…”