Prolonged periods of non-weightbearing activity result in a significant loss of bone mass which increases the risk of fracture with the initiation of mechanical loading. The loss of bone mass is partially driven by declines in bone formation yet the mechanisms responsible for this decline are unclear. To investigate the limitations of osteoblasts during disuse, marrow ablation was superimposed on hindlimb unloaded mice. Marrow ablation is a useful model to study osteoblast functionality as new cancellous bone is rapidly formed throughout the marrow of a long bone while hindlimb unloading is the most common method used to produce skeletal unloading. The specific hypotheses of this study were aimed at determining if changes in osteoblast functionality, differentiation, and/or proliferation were compromised in non-weightbearing bone in response to a bone formation stimulus. Additionally, the influence of having compromised osteoblast functionality at the time of stimulation was assessed in non-weightbearing bones. Key outcome measures used to address these hypotheses included static and dynamic cancellous bone histomorphometry, bone densitometry, and real-time polymerase chain reaction (PCR) analyses of gene expression. The results document similar ablation-induced increases of cancellous bone in both weightbearing and unloaded animals. Similarly, there was no influence of load on ablation-induced increases in cancellous bone forming surface or mineral apposition rate. Unloading did significantly attenuate the ablation-induced increase in bone formation rate, due to reduced levels of total surface mineralization. When osteoblast functionality was compromised prior to marrow ablation, bone formation rate increases were also attenuated in ablated animals due to reduced mineralization. Additionally, increases in forming surface were attenuated as compared to unloaded animals having normal osteoblast function at the time of ablation. Collectively, these data identify mineralization as the limiting step in new bone formation during periods of disuse. The caveat, however, is that when bone formation is stimulated after a period of unloading sufficient to compromise osteoblast functionality, increases in osteoblast recruitment to the bone surface are compromised.

Rats that undergo hindlimb unloading (HU) as a simulation for space flight experience bone changes similar to astronauts in microgravity. The purpose of this research was to assess whether an exercise countermeasure would be effective in preventing or mitigating bone degradation during HU. Controlled electrical muscle stimulation was applied to the lower left hindlimb to simulate resistive exercise. Adult 6-mo. old male rats were assigned to 3 groups of 12 each: hindlimb unloaded (HU), aging cage control (CC), and baseline (BL). The CC group was pair-fed to match the nutritional intake of HU animals during the 28 days of the study. The left leg was exercised 3 days a week for the duration of the study, with the unexercised right leg serving as a contra-lateral control. Mechanical tests were conducted to assess the strength of cancellous bone in the proximal tibia metaphysis. Although isolated specimens of cancellous bone are not feasible, reduced platen compression (RPC) was employed to directly load only the cancellous core region of each specimen. There was no significant difference in ultimate stress or elastic modulus between BL, CC, and HU-Ex (exercised). However, HU-Ex results were dramatically and significantly higher than HU-No Ex (contra-lateral unexercised control) for both ultimate stress (68%) and elastic modulus (81%). It is also notable that ultimate stress was 32% higher (but not statistically significant) for HU-Ex compared to CC. The total bone mineral density in the tibial metaphysis was significantly larger, 11%, in the HUEx compared to the HU-No Ex group's values. The results clearly demonstrate the efficacy of the exercise protocol in preventing the substantial mechanical deterioration induced by HU.

published_or_final_version / Mathematics / Master / Master of Philosophy

No description available.

A knowledge of the behavior of a material under loading similar to expected service loading is required before that material can be used effectively in the design process. Without sufficient mechanical properties data, the design process degenerates to a time consuming and often costly "build, test and modify" type of program. Obviously, this trial and error approach leaves much to be desired.

京都大学 / 0048 / 新制・課程博士 / 博士(人間健康科学) / 甲第19278号 / 人健博第30号 / 新制||人健||3(附属図書館) / 32280 / 京都大学大学院医学研究科人間健康科学系専攻 / (主査)教授 市橋 則明, 教授 三谷 章, 教授 松田 秀一 / 学位規則第4条第1項該当 / Doctor of Human Health Sciences / Kyoto University / DFAM

No description available.

Este trabalho buscou avaliar a técnica ultrassônica de Tempo de Voo da Onda Difratada (TOFD - Time-Of-Flight-Diffraction) para o monitoramento de trincas de fadiga nucleadas no interior de tubos de aço Superdúplex. Para isso, foram fabricados corpos de prova do tipo single edge bending SE(B) a partir de um tubo de aço Superdúplex sem costura. Estas amostras foram ensaiadas em fadiga, e o crescimento de trinca foi monitorado com as técnicas de TOFD, de Flexibilidade no Descarregamento (Compliance) – durante os ensaios, foram dadas sobrecargas mecânicas que causaram deformação plástica. As deformações serviram de pontos de referência para analisar o crescimento de trinca. Para aferir a validade os resultados obtidos com o TOFD nos ensaios de fadiga e fazer uma correlação com o monitoramento em campo de defeitos em tubos de aço Superdúplex, foi fabricado um padrão que simulou um tubo com defeito interno conhecido. Este padrão foi inspecionado com o TOFD, empregando os mesmos equipamentos e parâmetros utilizados nos ensaios de fadiga. Foi possível monitorar o crescimento de trinca em fadiga utilizando a técnica de TOFD e houve forte correlação entre os dados obtidos com o TOFD e o Compliance. A inspeção no tubo padrão manteve uma diferença entre a medida real e a obtida com o TOFD proporcional às encontradas durante o monitoramento dos ensaios de fadiga. / This study aimed to evaluate the ultrasonic technique Time-Of-Flight-Diffraction (TOFD) in monitoring fatigue nucleated cracks within super duplex steel pipes. In order to do it, single edge bending SE (B) specimens were manufactured using a super duplex steel seamless pipe. These samples were tested in fatigue and crack growth was monitored with two different techniques: TOFD and Flexibility in Unloading (Compliance). During the tests, it was used mechanical overloadings so deformation would be cause on the steel pipes. The deformations caused by that served as reference points to analyze the cracking growth. Thus, to assess the validity of the data obtained with the TOFD in fatigue tests, it was made a pattern that simulated a tube with known internal defect. This pattern was inspected with the TOFD, using the same equipment and parameters used in the fatigue tests. A correlation with the monitoring of defects field super duplex steel pipes was also made. The experiment has shown it is possible to monitor the cracking growth fatigue using the TOFD technique. Figures indicate, as well, there is a strong correlation between results obtained with the TOFD and Compliance. The inspection of the standard steel pipe maintained a difference between the actual measurement and obtained measurement. That difference was proportional from TOFD data and those found during the monitoring of the fatigue tests.

Thesis (M. Phil.)--University of Hong Kong, 2007. / Title proper from title frame. Also available in printed format.

Mechanical loading is an integral component to maintaining bone mass during periods of disuse (i.e. bedrest or casting) or reduced weightbearing activity. Recent data has shown a direct relation between the sympathetic nervous system (SNS) and bone metabolism, however the underlying mechanisms responsible for this relationship are unknown. Furthermore, the role that beta adrenergic stimulation during disuse has on cancellous bone mass and microarchitecture have yet to be defined. The central hypothesis of this research is that resistance exercise and beta-1 adrenergic (Adrb1) receptor agonist administration attenuate disuse-associated reductions in metaphyseal bone during 28 days of rodent hindlimb unloading (HU). Study one determined whether an eccentric- (ECC) or combined isometric+eccentric- (ISO+ECC) based contraction paradigm, engaged during hindlimb unloading (HU), mitigates losses in musculoskeletal mass and strength. Both simulated resistance training (SRT) protocols inhibited reductions in disuse-sensitive cancellous bone mass and maintained plantarflexor muscle strength. Study two determined whether combining the anabolic effects of SRT with the anti-resorptive effects of alendronate (ALEN) during HU positively impacts cancellous bone in an additive or synergistic fashion. ALEN significantly inhibited the anabolic response of cancellous bone to SRT during HU. Study three determined whether an Adrb1 receptor agonist (dobutamine; DOB) mitigates disuse-associated losses in bone mass and formation rate (BFR) during HU. DOB administration significantly blunted reductions in bone mineral density (vBMD) by maintaining cancellous BFR. Study four determined if Adrb1 receptor agonist administration during HU results in an attenuation of osteocyte apoptosis within cancellous bone and whether this relates to a decrease in Bax/Bcl-2 mRNA content ratio (pro- and anti-apoptotic proteins). HU significantly increased cancellous bone osteocyte apoptosis and Bax/Bcl-2 mRNA content ratio, which was reduced by the administration of DOB. Collectively, these are the first studies to assess the role of beta-1 adrenergic signaling and resistance exercise in mitigating disuse-induced loss of cancellous bone mass in rodents. The long term goals of this research are to understand the exact molecular mechanisms by which both Adrb1 signaling and high intensity resistance exercise provide beneficial bone effects during prolonged periods of disuse and to apply these findings to current osteoporosis research.