Made available in DSpace on 2014-06-11T19:25:37Z (GMT). No. of bitstreams: 0 Previous issue date: 2009-02-16Bitstream added on 2014-06-13T19:32:58Z : No. of bitstreams: 1 berchieri_cb_me_botfm.pdf: 270323 bytes, checksum: d429f18f90912ef77b56c68d82ce635d (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / O esqueleto é um dos maiores sistemas do corpo humano e é responsável pela manutenção da estrutura corporal e pelo armazenamento de minerais e proteínas, sendo a massa óssea determinada pela formação e reabsorção óssea. A osteoporose é um distúrbio osteometabólico crônico, multifatorial, relacionado à perda progressiva de massa óssea, geralmente de progressão assintomática até a ocorrência de fraturas. Caracteriza-se pela diminuição da densidade mineral óssea (DMO), com deterioração da microarquitetura óssea, que leva a um aumento da fragilidade esquelética e do risco de fraturas. As principais manifestações clínicas são as fraturas, sendo mais freqüentes as de vértebras, fêmur e antebraço. Desde 1949, quando Albright e Reifeinstein relataram a ocorrência de osteoporose em pacientes com diabetes (DM) de longa duração e mal-controlados, vários outros trabalhos foram publicados sobre o assunto, permanecendo não estabelecido o papel do DM como um fator de risco para osteoporose e fraturas ósseas. Avaliar a DMO e os possíveis fatores envolvidos em sua manutenção e formação, em adultos jovens com DM 1 e DM 2, comparando-os a um grupo controle homogêneo quanto à idade, gênero e índice de massa corpórea (IMC). Constituíram-se 2 grupos, sendo o primeiro de indivíduos com diabetes, subdividido em 25 indivíduos DM 1 e 25 indivíduos DM 2. O segundo grupo foi determinado como controle, composto por 18 indivíduos, os quais não apresentavam DM ou outras doenças que pudessem interferir no metabolismo ósseo e cuja faixa etária, gênero e IMC foram semelhantes aos diabéticos, compondo assim um grupo homogêneo. Os critérios de inclusão para os DM foram: idade entre 20 e 50 anos, tempo de diagnóstico do DM ≥5 anos, estar em acompanhamento ambulatorial, sem... / The skeleton is one of the largest systems in the human body and it is responsible for the maintenance of the body structure and also the storage of minerals and proteins. The bone mass is determined by the bone formation and reabsorption. Osteoporosis is a osteometabolic chronic multifactor disturb, related to progressive loss of bone mass, usually of asymptomatic progression until the occurrence of fractures. It is characterized by the decrease of the bone mineral density (BMD), with deterioration of the bone microarchitecture, which leads to a raise of the bone fragility and the risk of fractures. The main clinical manifestations are the fractures, more commonly on lumbar spine, femoral neck and forearm. Since 1949 when Albright & Reifeinstein described the occurrence of osteoporosis on long-term diabetic patients with poor metabolic control, many other studies were developed in this issue, remaining not well established the role of diabetes (DM) as a risk factor for osteoporosis and bone fractures. Assess the BMD and the possible factors involved in its maintenance and formation, in young type 1 and 2 diabetic adults, comparing them to a control group, alike on age, gender and body mass index (BMI). Two groups were established, the first one with type 1 (DM 1) and type 2 (DM 2) diabetic patients (25 individuals each) and the second one the control group, with 18 individuals without DM or any other disease which could affect bone metabolism. Age, gender and BMI were in parallel with the diabetic group characteristics, establishing a homogeneous group. Inclusion criteria for diabetic patients were: age between 20 and 50 years, diagnosis time ≥5 years, in actual clinical follow up, without further complications due to diabetes, not in use of drugs or having any disease which could interfere on bone metabolism, and non-pregnant or menopause women. A protocol was ...(Complete abstract click electronic access below)

Les contraintes mécaniques liées à la pratique physique jouent un rôle prépondérant dans l’optimisation de la masse, la géométrie et le métabolisme osseux. Pour ce travail, nous avons suivi pendant deux années une cohorte de 170 personnes âgées de 16-28 ans, pratiquant ou non un sport de haut niveau (>6heures/semaine). Nous avons décrit que lorsque la pratique sportive était débutée à l’adolescence et maintenue à l’âge adulte, le statut osseux était significativement meilleur par rapport à des individus non sportifs. D’autre part, plus les impacts mécaniques et l’intensité de pratique étaient élevés plus les valeurs osseuses biologiques de formation et densitométriques étaient importantes. Nous avons confirmé l’implication de la leptine et de l’insuline dans le métabolisme énergétique. Nous avons également validé une méthode novatrice d’analyse du tibia par la DXA et avons démontré que ce site osseux répondait fortement aux contraintes mécaniques. Afin d’étudier un modèle de masse corporelle extrême, nous avons spécifiquement étudié les rugbymen. Ils présentaient une hypoleptinémie significative avec une masse grasse similaire à celle des témoins, d’où probablement un effet direct de l’exercice physique sur le métabolisme de la leptine. Enfin, nous avons démontré que les paramètres osseux biologiques et densitométriques ne semblent plus évoluer significativement sur la période d’étude de deux ans. Les Pics de Masse et de Géométrie Osseuse semblent donc atteints, indépendamment du sexe et du statut sportif pour ce type de population d’adultes jeunes. / Mechanical strains induced by physical activity play an important role in bone mass, geometry and metabolism optimization. For this work, we have followed during 2 years, a cohort of 170 persons aged 16-30 years, who practiced or not a high level weight bearing sport (>6hours/week). We have described that when the practice was initiated during adolescence and maintained during adulthood, bone status was significantly greater compared to sedentary controls. Moreover, the more the mechanical impacts and practice intensity were, the higher bone formation rates and densitometry parameters were. We have confirmed the leptin and insulin implication in energy metabolism. We have also validated a new method to assess tibia bone parameters with DXA and we have demonstrated that this bone site strongly responded to mechanical strains. On the other hand, we have specifically studied rugby players as a model of “extreme” body composition. We have observed a significant hypoleptinaemia compared to controls whereas they had a similar fat mass: “extreme” practice would have a depressive action on leptin metabolism. Finally, we have showed that biology and densitometry bone parameters did not significantly evaluate whatever the bone site: Peak Bone Mass and Geometry appeared to be reached, independently of sex and sport status.

In this cross-sectional, retrospective study, the bone mineral content (BMC) and density (BMD) of the whole skeleton, upper limbs, lower limbs, femoral neck, and lumbar vertebrae were measured using dual photon absorptiometry and the results compared in healthy young males involved in: weight-lifting, running, cross-training, or recreational exercises. When adjusted for body weight, the upper limb BMD was highest in those engaged solely in weight-lifting, (mean 1.021, SE 0.019, and 95% CI 0.981-1.061) and lowest in runners (mean 0.908, SE 0.019 and 95% CI 0.869-0.946). These differences were significant (P = 0.0004). There were no significant differences in upper limb BMD between weight-lifters and cross-trained athletes and between runners and those engaged in recreational exercises. Significant differences in BMD were observed between weight-lifters and recreational athletes (P = 0.001) and between cross-trained athletes and runners (P = 0.03). No other significant differences were observed. These data suggest that healthy, young, adult males reporting a history of intensive weight-lifting had significantly greater bone mass of the upper limb bones than those reporting a history of non-weight-lifting exercises. These results imply a specific versus generalized effect of mechanical load on bones of the skeleton.

Sixty premenopausal women (age 25-50) finished a 16 week randomized controlled trial looking at the effects of different jump programs on hip and spine bone mineral density (BMD). Subjects were randomly assigned to a control group or one of two jumping groups. The Jump 10 group performed 10 jumps with 30 seconds of rest between jumps, twice daily, while the Jump 20 group performed the same protocol but with 20 jumps. At 8 weeks, BMD percent change (%Δ) at the hip was significantly different among groups when age, weight change, and subject compliance were simultaneously adjusted. In particular, the Jump 20 group had a greater %Δ in hip BMD compared to controls. However, %Δ in BMD for the neck of the hip (NOH), trochanter, or spine was not different among groups at 8 weeks. Following 16 weeks of jumping, BMD %Δ at the total hip and trochanter were significantly different among groups after adjusting for all covariates. Specifically, at the hip and trochanter, the Jump 10 and Jump 20 groups showed significantly greater %Δ in BMD compared to controls. There were no significant differences among groups for the BMD %Δ at NOH or spine at 16 weeks. Within-group analyses revealed no significant changes from baseline to 16 weeks for the jumping groups, but controls lost significant BMD. In conclusion, after 16 weeks of high-impact jump training, BMD at the hip and trochanter can be improved by jumping 10 or 20 times, twice daily, with 30 seconds of rest between each jump, compared to controls.

While osteoporosis is a major public health concern in the developed world, little research regarding factors influencing bone mineral accrual in children has been conducted in developing countries. South Africa is of particular interest since the incidence of hip fractures in South African Blacks has been reported to be amongst the lowest in the world (32; 253). In this thesis, the association of lifestyle factors; in particular physical activity (PA), socio economic status (SES) and dietary calcium intakes on the growing skeleton of Black and White South African children is investigated. After using accelerometry to validate a physical activity questionnaire (PAQ), in a convenience sample of South African Black, White, male and female children (n=30), fitness levels were assessed in a larger group (n=69) of similarly aged children, stratified by race and gender. Fittest subjects had significantly greater physical activity scores (p=0.022) as reported on the PAQ, lower body mass index’s (BMI) (p=0.001) and least percentage body fat (p=0.001) (as assessed using Dual Energy X-ray Absorptiometry (DXA), than least fit subjects. White males who reported to be significantly more active than all other groups on the PAQ were significantly fitter (p<0.001) than White females and Black males and females. The next study sought to determine whether differences observed in physical activity levels between groups showed an association with bone mineral content (BMC), density (BMD) and area (BA) (as assessed using DXA). PA was analyzed in terms of a metabolic (METPA; weighted metabolic score of intensity, frequency, and duration) and a mechanical (MECHPA;sum of all ground reaction forces multiplied by duration) component for 386 children aged 9.5 (0.04) years recruited from a longitudinal birth cohort study. White children expended a significantly greater energy score (METPA of 21.7 (2.9)) than Black children (METPA of 9.5 (0.5), p< 0.001). When children were divided into quartiles according to the amount and intensity of sport played, the most active White children had significantly higher (p<0.05) whole body BMD and higher hip and spine BMC and BMD after adjustment for body size than less active children. White children in the highest MECHPA quartile also showed significantly higher (p<0.05) whole body, hip, and spine BMC and BMD after adjustment for body size than those children in the lowest quartile. No association between PA and bone mass of Black children was found. No significant differences between METPA and MECHPA quartiles and BA were observed for any group. Given the disparate backgrounds from which many South African children come, the next study sought to determine whether differences in socio-economic status between Black and White South African children influence PA patterns. This study explored the relationship between socio-economic status, PA anthropometric and body composition (via DXA) variables in 381 children aged (9.5 (0.04) years) recruited from a longitudinal birth cohort study . Children falling into the highest socio-economic status quartile had mothers with the highest educational levels, generally came from dual parent homes, were most physically active, watched less television, weighed more and had greater lean tissue than children in lower socio-economic quartiles (p<0.001). Significantly greater levels of lean mass (p<0.001) with increased activity level were observed after controlling for television watching time and fat mass. There were high levels of low physical activity and high television watching time among lower socio-economic status groups. White children were found to be more active than Black children, more likely to be offered physical education and to participate in physical education classes at school and watched less television than Black children. The final study sought to investigate the association between habitual PA patterns and dietary calcium intakes with bone mass acquisition over a one year period in 321 pre-pubertal South African children recruited from a longitudinal birth cohort study. Data were analyzed by regressing change in BMC and BA from age nine to ten years, against BA (for BMC), height and body weight. The residuals were saved and called residualized BMCGAIN and BAGAIN. Residualized values provide a good indication of weight, height and BA-matched accumulation rates. White children had significantly higher PA levels and calcium intakes than Black children. Most active White males had significantly higher residualized BMCGAIN and BAGAIN at the whole body, hip and spine but not at the radius, than those who were less active. Most active White females had significantly higher residualized BAGAIN at all sites except the radius than less-active girls. No such effects were seen in Black children. There was no interactive effect on residualized BMCGAIN or BAGAIN for calcium intake and PA in boys or Black girls, but an interactive and possible synergistic effect of calcium and physical activity was observed at the spine, radius and hip in White girls. In this population, PA has an osteogenic association with White children, but not Black children, which may be explained by the lower levels of PA in the Black children. Despite this, Black children had significantly greater bone mass at the hip and spine (girls only) (p< 0.001) even after adjustment for body size.In conclusion, differences between White and Black children’s PA levels were observed, with White children reporting higher PA levels and exhibiting higher fitness levels than Black children. Physical fitness correlated well with self reported physical activity levels on the PAQ and objectively measured body composition. Socio-economic status differences between White and Black children are highly related to differences in physical activity patterns and body composition profiles. Bone mass and area gain is accentuated in pre- and early-pubertal children with highest levels of habitual physical activity. Limited evidence of an effect of dietary calcium intakes on bone mass in boys and Black girls was found. The role of exercise in increasing bone mass may become increasingly critical as a protective mechanism against osteoporosis in both South African race groups, especially because the genetic benefit exhibited by Black children to higher bone mass may be weakened with time, as environmental influences become stronger.

The foundation for osteoporosis risk is established during the time periods of childhood, adolescence, and young adulthood, periods of development when bone mass is being accrued rapidly. The relative quantity of bone mass accrued is influenced by both lifestyle and genetic factors. The purpose of this dissertation project was to discover single nucleotide polymorphisms (SNPs) associated with: (1) The rate of hip bone accrual (measured as bone mineral content or BMC) during the adolescent growth spurt, and (2) Total hip bone mass measured as BMC around the age of 19 when the amount of bone accrued is approximately at its peak. Additionally, SNP × longitudinal lifestyle factor (calcium intake per day, vitamin D intake per day, and minutes of moderate to vigorous physical activity (MVPA) per day) multiplicative interaction effects were assessed. Each cohort member’s vector of longitudinal physical activity measurements was summarized as belonging to one of a set of specific trajectory groups using finite mixture modeling. The same was then done for calcium intake and vitamin D intake. The source of the data utilized was the Iowa Bone Development Study (IBDS), which includes genetic and longitudinal bone measurement information. To discover SNPs, a genome-wide association study (GWAS) design was utilized. Females and males were analyzed separately and together. The association between SNPs and the rate of hip bone accrual during the adolescent growth spurt was assessed using linear mixed models controlling for body size, and the association between SNPs and peak hip bone mass was assessed using an ordinary linear regression model, also controlling for body size. Approximately 500,000 SNPs were tested in each GWA analysis; significance was assessed at a familywise error rate of 0.05, the individual test cutoff of which was determined by using SimpleM, a modified Šídák correction. No statistically significant SNPs were detected at the 0.05 familywise error rate threshold established by SimpleM (p < 1.76×10-7); however genes near suggestive SNPs (24 total) were assessed for biological relevance. Of most biological relevance were two suggestive SNPs (rs2051756 and rs2866908, p-values of 1.25×10-6 and 4.28×10-6, respectively) that were detected in an intron of the DKK2 gene through the GWA analysis exploring peak bone mass in females. The DKK2 gene is part of the Wnt signaling pathway and is associated with embryonic development; additionally, it is expressed more highly in osteoarthritic osteoblasts than in normal osteoblasts. No statistically significant results were found from the SNP × lifestyle factor multiplicative interaction effect tests. The potential importance of the DKK2 gene to peak hip bone mass accrual in females should be studied further in order to understand the pathophysiology of this suggested novel association identified during a discovery GWA analysis.

Orientador: Walkyria de Paula Pimenta / Banca: Glaucia Mazeto / Banca: Rosa dos Santos / Resumo: O esqueleto é um dos maiores sistemas do corpo humano e é responsável pela manutenção da estrutura corporal e pelo armazenamento de minerais e proteínas, sendo a massa óssea determinada pela formação e reabsorção óssea. A osteoporose é um distúrbio osteometabólico crônico, multifatorial, relacionado à perda progressiva de massa óssea, geralmente de progressão assintomática até a ocorrência de fraturas. Caracteriza-se pela diminuição da densidade mineral óssea (DMO), com deterioração da microarquitetura óssea, que leva a um aumento da fragilidade esquelética e do risco de fraturas. As principais manifestações clínicas são as fraturas, sendo mais freqüentes as de vértebras, fêmur e antebraço. Desde 1949, quando Albright e Reifeinstein relataram a ocorrência de osteoporose em pacientes com diabetes (DM) de longa duração e mal-controlados, vários outros trabalhos foram publicados sobre o assunto, permanecendo não estabelecido o papel do DM como um fator de risco para osteoporose e fraturas ósseas. Avaliar a DMO e os possíveis fatores envolvidos em sua manutenção e formação, em adultos jovens com DM 1 e DM 2, comparando-os a um grupo controle homogêneo quanto à idade, gênero e índice de massa corpórea (IMC). Constituíram-se 2 grupos, sendo o primeiro de indivíduos com diabetes, subdividido em 25 indivíduos DM 1 e 25 indivíduos DM 2. O segundo grupo foi determinado como controle, composto por 18 indivíduos, os quais não apresentavam DM ou outras doenças que pudessem interferir no metabolismo ósseo e cuja faixa etária, gênero e IMC foram semelhantes aos diabéticos, compondo assim um grupo homogêneo. Os critérios de inclusão para os DM foram: idade entre 20 e 50 anos, tempo de diagnóstico do DM ≥5 anos, estar em acompanhamento ambulatorial, sem ...(Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The skeleton is one of the largest systems in the human body and it is responsible for the maintenance of the body structure and also the storage of minerals and proteins. The bone mass is determined by the bone formation and reabsorption. Osteoporosis is a osteometabolic chronic multifactor disturb, related to progressive loss of bone mass, usually of asymptomatic progression until the occurrence of fractures. It is characterized by the decrease of the bone mineral density (BMD), with deterioration of the bone microarchitecture, which leads to a raise of the bone fragility and the risk of fractures. The main clinical manifestations are the fractures, more commonly on lumbar spine, femoral neck and forearm. Since 1949 when Albright & Reifeinstein described the occurrence of osteoporosis on long-term diabetic patients with poor metabolic control, many other studies were developed in this issue, remaining not well established the role of diabetes (DM) as a risk factor for osteoporosis and bone fractures. Assess the BMD and the possible factors involved in its maintenance and formation, in young type 1 and 2 diabetic adults, comparing them to a control group, alike on age, gender and body mass index (BMI). Two groups were established, the first one with type 1 (DM 1) and type 2 (DM 2) diabetic patients (25 individuals each) and the second one the control group, with 18 individuals without DM or any other disease which could affect bone metabolism. Age, gender and BMI were in parallel with the diabetic group characteristics, establishing a homogeneous group. Inclusion criteria for diabetic patients were: age between 20 and 50 years, diagnosis time ≥5 years, in actual clinical follow up, without further complications due to diabetes, not in use of drugs or having any disease which could interfere on bone metabolism, and non-pregnant or menopause women. A protocol was ...(Complete abstract click electronic access below) / Mestre

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N/A / Thesis / Master of Science (MS)