scholarly journals Interrelation between external oscillatory muscle coupling amplitude and in vivo intramedullary pressure related bone adaptation

Bone ◽  
2014 ◽  
Vol 66 ◽  
pp. 178-181 ◽  
Author(s):  
Minyi Hu ◽  
Jiqi Cheng ◽  
Neville Bethel ◽  
Frederick Serra-Hsu ◽  
Suzanne Ferreri ◽  
...  
Author(s):  
M. Hu ◽  
J. Cheng ◽  
S. Ferreri ◽  
F. Serra-Hsu ◽  
W. Lin ◽  
...  

Bone loss is a critical health problem of astronauts in long-term space missions. A growing number of evidence has pointed out bone fluid flow as a critical regulator in mechanotransductive signaling and bone adaptation. Intramedullary pressure (ImP) is a key mediator for bone fluid flow initiation and it influences the osteogenic signals within the skeleton. The potential ImP-induced bone fluid flow then triggers bone adaptation [1]. Previous in vivo study has demonstrated that ImP induced by oscillatory electrical stimulations can effectively mitigate disuse osteopenia in a frequency-dependent manner in a disuse rat model [2, 3]. In order to develop the translational potentials of ImP, a non-invasive intervention with direct fluid flow coupling is necessary to develop new treatments for microgravity-induced osteopenia/osteoporosis.


1999 ◽  
Vol 360 ◽  
pp. 136-146 ◽  
Author(s):  
Siegfried Hofmann ◽  
Reinhard Hopf ◽  
Gerald Mayr ◽  
Gerhard Schlag ◽  
Martin Salzer

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.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Haisheng Yang ◽  
Alexander Büttner ◽  
Laia Albiol ◽  
Catherine Julien ◽  
Tobias Thiele ◽  
...  

AbstractLoss-of-function mutations in the Sost gene lead to high bone mass phenotypes. Pharmacological inhibition of Sost/sclerostin provides a new drug strategy for treating osteoporosis. Questions remain as to how physical activity may affect bone mass under sclerostin inhibition and if that effect differs between males and females. We previously observed in female Sost knockout (KO) mice an enhanced cortical bone formation response to a moderate level of applied loading (900 με at the tibial midshaft). The purpose of the present study was to examine cortical bone adaptation to the same strain level applied to male Sost KO mice. Strain-matched in vivo compressive loading was applied to the tibiae of 10-, 26- and 52-week-old male Sost KO and littermate control (LC) mice. The effect of tibial loading on bone (re)modeling was measured by microCT, 3D time-lapse in vivo morphometry, 2D histomorphometry and gene expression analyses. As expected, Sost deficiency led to high cortical bone mass in 10- and 26-week-old male mice as a result of increased bone formation. However, the enhanced bone formation associated with Sost deficiency did not appear to diminish with skeletal maturation. An increase in bone resorption was observed with skeletal maturation in male LC and Sost KO mice. Two weeks of in vivo loading (900 με at the tibial midshaft) induced only a mild anabolic response in 10- and 26-week-old male mice, independent of Sost deficiency. A decrease in the Wnt inhibitor Dkk1 expression was observed 3 h after loading in 52-week-old Sost KO and LC mice, and an increase in Lef1 expression was observed 8 h after loading in 10-week-old Sost KO mice. The current results suggest that long-term inhibition of sclerostin in male mice does not influence the adaptive response of cortical bone to moderate levels of loading. In contrast with our previous strain-matched study in females showing enhanced bone responses with Sost ablation, these results in males indicate that the influence of Sost deficiency on the cortical bone formation response to a moderate level of loading differs between males and females. Clinical studies examining antibodies to inhibit sclerostin may need to consider that the efficacy of additional physical activity regimens may be sex dependent.


2015 ◽  
Vol 137 (1) ◽  
Author(s):  
Varun A. Bhatia ◽  
W. Brent Edwards ◽  
Joshua E. Johnson ◽  
Karen L. Troy

Bone adaptation is understood to be driven by mechanical strains acting on the bone as a result of some mechanical stimuli. Although the strain/adaptation relation has been extensively researched using in vivo animal loading models, it has not been studied in humans, likely due to difficulties in quantifying bone strains and adaptation in living humans. Our purpose was to examine the relationship between bone strain and changes in bone mineral parameters at the local level. Serial computed tomography (CT) scans were used to calculate 14 week changes in bone mineral parameters at the distal radius for 23 women participating in a cyclic in vivo loading protocol (leaning onto the palm of the hand), and 12 women acting as controls. Strains were calculated at the distal radius during the task using validated finite element (FE) modeling techniques. Twelve subregions of interest were selected and analyzed to test the strain/adaptation relation at the local level. A positive relationship between mean energy equivalent strain and percent change in bone mineral density (BMD) (slope = 0.96%/1000 με, p < 0.05) was observed within experimental, but not control subjects. When subregion strains were grouped by quartile, significant slopes for quartile versus bone mineral content (BMC) (0.24%/quartile) and BMD (0.28%/quartile) were observed. Increases in BMC and BMD were greatest in the highest-strain quartile (energy equivalent strain > 539 με). The data demonstrate preliminary prospective evidence of a local strain/adaptation relationship within human bone. These methods are a first step toward facilitating the development of personalized exercise prescriptions for maintaining and improving bone health.


2005 ◽  
Vol 898 ◽  
Author(s):  
David H. Kohn ◽  
Nadder D. Sahar ◽  
Sun Ig Hong ◽  
Kurtulus Golcuk ◽  
Michael D. Morris

AbstractSkeletal fractures represent a significant medical and economic burden for society. It is generally thought that a high incidence of musculoskeletal fatigue loading results in damage accumulation at too high of a rate to be efficiently remodeled, leading to skeletal fracture. The state of damage in bone at a given time is therefore the net result of damage and repair processes, and is dependent upon extrinsic factors such as mechanical history, but also upon intrinsic factors, such as composition of bone mineral and matrix. In this invited paper, we review investigations on the coupling of Raman spectroscopy with mechanical loading of bone, providing insight into mechanisms of ultrastructural deformation in bone at smaller scales than previously understood. We also present new data showing that in-vivo mechanical loading results in increased resistance to fatigue damage, coupled with an increase in phosphate to amide I ratio and decrease in carbonate to phosphate ratio. Taken together, the data demonstrates the ability to modulate the mechanical and chemical properties of bone via exogenous mechanical stimulation.


2018 ◽  
Vol 15 (141) ◽  
pp. 20180012 ◽  
Author(s):  
Laia Albiol ◽  
Myriam Cilla ◽  
David Pflanz ◽  
Ina Kramer ◽  
Michaela Kneissel ◽  
...  

Sclerostin, a product of the Sost gene, is a Wnt-inhibitor and thus negatively regulates bone accrual. Canonical Wnt/β-catenin signalling is also known to be activated in mechanotransduction. Sclerostin neutralizing antibodies are being tested in ongoing clinical trials to target osteoporosis and osteogenesis imperfecta but their interaction with mechanical stimuli on bone formation remains unclear. Sost knockout (KO) mice were examined to gain insight into how long-term Sost deficiency alters the local mechanical environment within the bone. This knowledge is crucial as the strain environment regulates bone adaptation. We characterized the bone geometry at the tibial midshaft of young and adult Sost KO and age-matched littermate control (LC) mice using microcomputed tomography imaging. The cortical area and the minimal and maximal moment of inertia were higher in Sost KO than in LC mice, whereas no difference was detected in either the anterior–posterior or medio-lateral bone curvature. Differences observed between age-matched genotypes were greater in adult mice. We analysed the local mechanical environment in the bone using finite-element models (FEMs), which showed that strains in the tibiae of Sost KO mice are lower than in age-matched LC mice at the diaphyseal midshaft, a region commonly used to assess cortical bone formation and resorption. Our FEMs also suggested that tissue mineral density is only a minor contributor to the strain distribution in tibial cortical bone from Sost KO mice compared to bone geometry. Furthermore, they indicated that although strain gauging experiments matched strains at the gauge site, strains along the tibial length were not comparable between age-matched Sost KO and LC mice or between young and adult animals within the same genotype.


Author(s):  
M. Hu ◽  
R. Yeh ◽  
M. Lien ◽  
Y. X. Qin

Osteoporosis is a debilitating disease characterized as decreased bone mass and structural deterioration of bone tissue. Osteoporotic bone tissue turns itself into altered structure, which leads to weaker bones that are more susceptible for fractures. While often happening in elderly, long-term bed-rest patients, e.g. spinal cord injury, and astronauts who participate in long-duration spaceflights, osteoporosis has been considered as a major public health thread and causes great medical cost impacts to the society. Mechanobiology and novel stimulation on regulating bone health have long been recognized. Loading induced bone fluid flow, as a critical mechanotransductive promoter, has been demonstrated to regulate cellular signaling, osteogenesis, and bone adaptation [4]. As one of the factors that mediate bone fluid flow, intromedullary pressure (ImP) creates a pressure gradient that further influence the magnitude of mechanotransductory signals [5]. As for a potential translational development of ImP, our group has recently introduced a novel, non-invasive dynamic hydraulic stimulation (DHS) on bone structural enhancement. Its promising effects on inhibition of disuse bone loss has been shown with 2 Hz loading through a 4-week hindlimb suspension rat study followed by microCT analysis. At the cellular level, mesenchymal stem cells (MSCs) are defined by their self-renewal ability and that to potentially differentiate into the cells that form tissues such as bone [1]. To further elucidate the cellular effects of DHS and its potential mechanism on bone quality enhancement, the objective of this study was to measure MSC quantification in response to the in vivo mechanical signals driven by DHS.


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