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NASA goals include long-term International Space Station (ISS) missions and the ambitious objective of eventually sending astronauts to Mars. Unfortunately, exposure to unloading due to microgravity during spaceflight has been shown to cause detrimental health effects on bone. Therefore, NASA is seeking a ground-based animal model to study the long-term effects of unloading on bone in order to better insure the health and mission capability of astronauts. The hindlimb unloaded (HU) rat model was used to study the effects of multiple unloading exposures and aging on bone properties. Six month old, adult, male Sprague-Dawley rats were separated into the following groups: baseline (BL, sacrificed when received at 6 months age), aging cage control (AC, normal weight-bearing cage activity), 1HU7 (unloaded for 1 month starting at 7 months of age and allowed to recover for 3 months), 1HU10 (normal cage activity until 10 months of age, unloaded for 1 month, recovered for 2 months), and 2HU10 (unloaded for 1 month at 7 months of age, allowed to recover for 2 months, unloaded again for 1 month at 10 months of age, followed by 2 months of recovery). Every 28 days a subset of animals (n=15) were euthanized and both femurs were excised. A peripheral quantitative computed tomography (pQCT) scanner was used to collect densitometric and geometric properties at the right and left femoral neck and at the left femoral midshaft. Mechanical testing (axial and lateral compression of the femoral neck and 3pt bending of the midshaft) was performed at each location and strength indices based on pQCT parameters were calculated. Femoral neck properties decreased due to HU but recovered with respect to increase over HU, BL, and AC by the end of the recovery periods. Femoral midshaft properties were relatively unaffected, but did show slight decreases for older animals at month 10, which recovered during the two month recovery period. Femoral neck geometry exhibited increased endocortical resorption and periosteal apposition of the cortical shell which suggests that trabecular bone plays an important role in how the total bone is affected by HU. Densitometric properties were affected less by HU with respect to BL than were mechanical strength values. Results suggest that femoral neck is more affected by unloading than midshaft, particularly for multiple exposures of unloading. Also, aging does not appear to be a critical factor for bone loss due to HU for either femoral neck or midshaft.

Orientador: Horácio Faig Leite. / Banca: João Batista César Neto / Banca: Raquel Guedes Fernandes Pires / Banca: Maria Aparecida Neves Jardini / Banca: Warley David Kerbauy / Resumo: O objetivo desse estudo foi avaliar o efeito do uso local de uma solução aquosa de risendronato de sódio (RS) em diferentes concentrações na inibição da perda óssea alveolar decorrente de periodontite experimental induzida em ratas. Os 48 animais foram divididos em 2 grupos constituídos por 24 animais: GD (dupla aplicação) e GU (única aplicação). Os dois grupos foram subdivididos em 8 subgrupos: R1 (duas aplicações de 0,125 mg de RS), R2 (duas aplicações de 0,25 mg de RS), R3 (duas aplicações de 0,5 mg de RS) e A1 (duas aplicações de água destilada); R4 (uma aplicação de 0,125 mg de RS), R5 (uma aplicação de 0,25 mg de RS), R6 (uma aplicação de 0,5 mg de RS) e A2 (uma aplicação de água destilada). Foi induzida a periodontite pela confecção de ligaduras ao redor dos primeiros molares inferiores direitos em todos os animais. Nos grupos A1 e A2, os molares contralaterais serviram de controles negativos (C1 e C2). A medicação foi aplicada aos 5 e 10 dias após indução da periodontite nos animais do GD, e nos animais do GU apenas aos 10 dias. Decorrente 15 dias os animais foram submetidos à eutanásia. Foram feitas análises histológica, histomorfométrica, imuno-histoquímica anti-osteocalcina e enzimo-histoquímica para TRAP (fosfatase ácida tartarato resistente). Os grupos que receberam RS exibiram maior volume trabecular da crista óssea remanescente que o controle significante estatísticamente, mas não foram observados diferenças entre os grupos tratados. A perda óssea alveolar foi menor nos grupos tratados com risendronato comparado com controle e foi dose-dependente. Os grupos que receberam a menor dose (R1 e R4) apresentaram menor perda óssea estatisticamente... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The aim of this study was to evaluate the local use of an aqueous solution of sodium risendronate (RS) at different concentrations on the inhibition of alveolar bone loss caused by experimental periodontitis induced in rats. The 48 animals were divided into two groups consisting of 24 animals: GD (double application) and GU (one application). The two groups were subdivided into eight subgroups: A1 (two applications of 0.125 mg RS), R2 (two applications of 0.25 mg RS), R3 (two applications of 0.5 mg RS) and A1 (two applications of distilled water), and R4 (one application of 0.125 mg RS), R5 (one application of 0.25 mg RS), R6 (one application of 0.5 mg RS) and A2 (one applications with distilled water). Periodontitis was induced in first molars in all animals. In groups A1 and A2, the contralateral molars served as controls (C1 and C2). The medication was applied at 5 and 10 days after induction of periodontitis in animals of GD, and animals of GU only after 10 days. After 15 days the animals were euthanized. Analysis was performed on histological, histomorphometric, immunohistochemical antiosteocalcin and enzimohistochemical for TRAP (tartrate resistant acid phosphatase). The groups that received RS exhibited greater volume of trabecular bone crest that controlling statistically significant, but no differences were observed between treated groups. The alveolar bone loss was lower in treated groups compared with placebo and was dose-dependent. The groups that received the lowest dose (R1 and R4) showed statistically significant less bone loss than the intermediate dose (R2 and R5), which in turn exhibited lower rates compared with higher doses (R3 and R6). The two types of approaches, however, did not show statistical significance. The number of TRAP-positive cells was... (Complete abstract click electronic access below) / Doutor

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Bone loss is an important skeletal indicator of environmental stress. Cortical and trabecular bone, however, are differentially affected by various stressors. Peripheral quantitative computed tomography (pQCT) potentially addresses this issue by separately calculating cortical and trabecular bone mineral density (BMD). This project had two major goals: evaluate the effectiveness of pQCT in measuring BMD in archaeological specimens, and test the hypothesis that females suffered greater bone loss than males in a socially stressed population. Cortical and trabecular BMD was measured in the radius and femur of skeletons from Point of Pines Pueblo, Arizona. pQCT effectively measured BMD in the sample, but the hypothesis that females suffered greater BMD loss than males was not supported. Females showed no significant BMD loss in the radius, while males experienced no significant changes in cortical density. Sex-specific activities may explain bone maintenance in the female radius, while hormonal differences likely maintained male cortical density.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2005. / Härtill 4 uppsatser.