An Improved In Vivo Rat Tail Vertebra Model for the Study of Trabecular Bone Adaptation

1999 ◽  
Author(s):  
Mark J. Eichler ◽  
Chi Hyun Kim ◽  
X. Edward Guo

Abstract The role of mechanical loading in trabecular bone adaptation is important for the understanding of bone integrity in different loading scenarios such as microgravity and for the etiology of age-related bone fractures. There have been numerous in vivo animal studies of bone adaptation, most of which are related to cortical bone remodeling, aimed at the investigation of Wolff’s Law [4], An interesting experimental model for trabecular bone adaptation has been developed in the rat tail vertebrae [2,3]. This model is attractive for trabecular bone adaptation studies because a controlled mechanical load can be applied to a whole vertebra with minimal surgical trauma, using a relatively inexpensive animal model. In addition, with advanced micro computed tomography (micro-CT) or micro magnetic resonance imaging (micro-MRI) coupled with large scale finite element modeling techniques, it is possible to characterize the three-dimensional (3D) stress/strain environment in the bone tissue close to a cellular level (∼25μm) [1]. Therefore, this in vivo rat tail model has a tremendous potential for quantification of the relationship between mechanical stimulation and biological response in trabecular bone adaptation.

Author(s):  
Chi Hyun Kim ◽  
Erica Takai ◽  
Nicole Culella ◽  
X. Edward Guo

The study of bone adaptation is important in understanding the etiology of age-related bone fractures, developing optimal designs for total joint replacements, and preventing bone loss during prolonged space flight. Numerous studies have attempted to quantify the relationship between mechanical loading and bone adaptation [1,2,3,4]. An in vivo rat tail vertebra model has been developed for trabecular bone adaptation studies where a controlled mechanical load can be applied to a whole vertebra [3]. The load levels applied in vivo were selected using in vitro strain gage measurements on cadaveric rat tails, resulting strains in the cortical shell of tail vertebrae within the physiological range. However, it is not clear what the physiological strain level in the rat tail vertebrae in vivo during normal cage activities is. In addition, the in vivo strain in the rat tail vertebra subjected to mechanical loads has not been quantified.


2000 ◽  
Author(s):  
Mark J. Eichler ◽  
Chi Hyun Kim ◽  
Ralph Müller ◽  
X. Edward Guo

Abstract Age-related bone fractures are mostly influenced by trabecular bone sites. Trabecular bone constantly adapts its bone volume fraction (BV/TV) and orientation, and thus its mechanical properties, to mechanical usage. Therefore, understanding the trabecular bone adaptation process and its consequences will contribute to the better understanding of the etiology of age-related fractures. Micro-computed tomography (micro-CT) is a relatively new method to quantify the complex three-dimensional (3D) trabecular bone architecture [1,2]. Finite element computational studies can be performed on these 3D microstructural images by converting each image voxel into an element [3,4,5]. Image thresholding techniques to segment bone voxels from bone marrow voxels have a major impact on the results of these models. However, the influence of different types of thresholding techniques on the mechanical properties of bone has not been examined carefully.


2012 ◽  
Vol 33 (1) ◽  
pp. 146-156 ◽  
Author(s):  
Roa Harb ◽  
Christina Whiteus ◽  
Catarina Freitas ◽  
Jaime Grutzendler

Cerebral function and viability are critically dependent on efficient delivery of oxygen and glucose through the microvasculature. Here, we studied individual microvessels in the intact brain using high-resolution confocal imaging and long-term time-lapse two-photon microscopy across the lifetime of a mouse. In the first postnatal month, we found large-scale sprouting but to our surprise the majority of sprouts underwent pruning and only a small fraction became perfused capillaries. After the first month, microvessel formation and elimination decreased and the net number of vessels stabilized. Although vascular stability was the hallmark of the adult brain, some vessel formation and elimination continued throughout life. In young adult mice, vessel formation was markedly increased after exposure to hypoxia; however, upon return to normoxia, no vessel elimination was observed, suggesting that new vessels constitute a long-term adaptive response to metabolic challenges. This plasticity was markedly reduced in older adults and aging where hypoxia-induced angiogenesis was absent. Our study describes, for the first time in vivo patterns of cerebral microvascular remodeling throughout life. Disruption of the observed balance between baseline turnover and vascular stability may underlie a variety of developmental and age-related degenerative neurological disorders.


Bone ◽  
2009 ◽  
Vol 44 ◽  
pp. S300 ◽  
Author(s):  
F.M. Lambers⁎ ◽  
G. Kuhn ◽  
F.A. Gerhard ◽  
R. Muller

2020 ◽  
Vol 287 (1926) ◽  
pp. 20200457 ◽  
Author(s):  
Stephanie M. Smith ◽  
Kenneth D. Angielczyk

Biological structures with extreme morphologies are puzzling because they often lack obvious functions and stymie comparisons to homologous or analogous features with more typical shapes. An example of such an extreme morphotype is the uniquely modified vertebral column of the hero shrew Scutisorex , which features numerous accessory intervertebral articulations and massively expanded transverse processes. The function of these vertebral structures is unknown, and it is difficult to meaningfully compare them to vertebrae from animals with known behavioural patterns and spinal adaptations. Here, we use trabecular bone architecture of vertebral centra and quantitative external vertebral morphology to elucidate the forces that may act on the spine of Scutisorex and that of another large shrew with unmodified vertebrae ( Crocidura goliath ). X-ray micro-computed tomography (µCT) scans of thoracolumbar columns show that Scutisorex thori is structurally intermediate between C. goliath and S. somereni internally and externally, and both Scutisorex species exhibit trabecular bone characteristics indicative of higher in vivo axial compressive loads than C. goliath. Under compressive load, Scutisorex vertebral morphology is adapted to largely restrict bending to the sagittal plane (flexion). Although these findings do not solve the mystery of how Scutisorex uses its byzantine spine in vivo , our work suggests potentially fruitful new avenues of investigation for learning more about the function of this perplexing structure.


2014 ◽  
Vol 29 (4) ◽  
pp. 355-362 ◽  
Author(s):  
Alina Levchuk ◽  
Alexander Zwahlen ◽  
Claudia Weigt ◽  
Floor M. Lambers ◽  
Sandro D. Badilatti ◽  
...  

2015 ◽  
Vol 43 (03) ◽  
pp. 513-528 ◽  
Author(s):  
Qiao-Han Wang ◽  
Xiao-Lin Yang ◽  
Wei Xiao ◽  
Zhen-Zhong Wang ◽  
Gang Ding ◽  
...  

Akebia Saponin D (ASD) or asperosaponin VI is the most abundant constituent of the rhizome of Dipsacus asper, which has been used for the treatment of lower back pain, traumatic hematoma and bone fractures. In recent years, it was reported that ASD was a potential treatment strategy for Alzheimer's disease (AD). However, the low bioavailability of ASD limited its clinical utility. Microcrystalline preparation is one of the effective methods to improve drug absorption. The drugs prepared by different methods can present different solid forms (polymorphs), and different polymorphs have significantly different bioavailabilities. The objective of this study was to prepare ASD polymorphs using the different preparation processes and to evaluate their physicochemical properties and oral absorption. ASD-2 obtained by the antisolvent process was simpler and had higher recovery (78.5%) than that of ASD-1 by a two-step macroporous resin column separation (56.5%). The ASD polymorphs were characterized using differential scanning calorimetry (DSC), thermogravimetry analysis (TGA), powder X-ray diffraction (PXRD) and scanning electron microscopy (SEM). The results revealed that ASD-2 existed in microcrystalline form, while ASD-1 was amorphous. Furthermore, the equilibrium solubility, dissolution in aqueous solution and pharmacokinetic parameters of the samples were determined. ASD-2 showed lower aqueous solubility than that of ASD-1 (p < 0.01). In addition, ASD-2 showed lower dissolution with only 65% of the drug released while ASD-1 had a higher dissolution with 99% of drug released at the end of the 180 min testing period. Although ASD-1 significantly increased solubility and dissolution, the AUC 0-20h of ASD-2 was 4.3 times that of the amorphous ASD-1 in vivo. Data suggest that the microcrystalline preparation of ASD-2 is not only reasonable in economy and suitable for large-scale preparation, but also a promising method to enhance bioavailability of ASD.


Author(s):  
Xiaowei S. Liu ◽  
X. Henry Zhang ◽  
Paul Sajda ◽  
Punam K. Saha ◽  
Felix W. Wehrli ◽  
...  

Osteoporosis is an age-related disease characterized by low bone mass and architectural deterioration. Other than bone volume fraction (BV/TV), microarchitecture of trabecular bone, such as trabecular type (rods or plates), connectivity, and orientation of the trabecular network is also believed to be important in governing the mechanical properties of trabecular bone. A recent study [1] showed that the microarchitecture alone affects elastic moduli of trabecular bone and, further, that trabecular plates make a far greater contribution than rods. In human vertebral trabecular bone, the roles of transverse vs. vertical rods in conferring mechanical properties of trabecular bone have been debated [2, 3]. It has been suggested that the role of transverse trabecular rod is critical in determining elastic modulus of vertebral trabecular bone. However, without explicit classifications of trabecular type, or orientation assessment at an individual trabecula level, it is not possible yet to test this hypothesis in human trabecular bone samples despite the development of three-dimensional (3D) micro computed tomography (μCT) and μCT based finite element (FE) models of human trabecular bone. With the newly developed technique of complete volumetric decomposition and individual trabecula based orientation analyses [4], now it is possible to quantitatively examine the contributions of trabecular rods of various orientations in the elastic properties of vertebral trabecular bone.


2020 ◽  
Vol 117 (51) ◽  
pp. 32251-32259
Author(s):  
Alexander Franciscus van Tol ◽  
Victoria Schemenz ◽  
Wolfgang Wagermaier ◽  
Andreas Roschger ◽  
Hajar Razi ◽  
...  

Organisms rely on mechanosensing mechanisms to adapt to changes in their mechanical environment. Fluid-filled network structures not only ensure efficient transport but can also be employed for mechanosensation. The lacunocanalicular network (LCN) is a fluid-filled network structure, which pervades our bones and accommodates a cell network of osteocytes. For the mechanism of mechanosensation, it was hypothesized that load-induced fluid flow results in forces that can be sensed by the cells. We use a controlled in vivo loading experiment on murine tibiae to test this hypothesis, whereby the mechanoresponse was quantified experimentally by in vivo micro-computed tomography (µCT) in terms of formed and resorbed bone volume. By imaging the LCN using confocal microscopy in bone volumes covering the entire cross-section of mouse tibiae and by calculating the fluid flow in the three-dimensional (3D) network, we could perform a direct comparison between predictions based on fluid flow velocity and the experimentally measured mechanoresponse. While local strain distributions estimated by finite-element analysis incorrectly predicts preferred bone formation on the periosteal surface, we demonstrate that additional consideration of the LCN architecture not only corrects this erroneous bias in the prediction but also explains observed differences in the mechanosensitivity between the three investigated mice. We also identified the presence of vascular channels as an important mechanism to locally reduce fluid flow. Flow velocities increased for a convergent network structure where all of the flow is channeled into fewer canaliculi. We conclude that, besides mechanical loading, LCN architecture should be considered as a key determinant of bone adaptation.


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