Origin of renal osteodystrophy and cardiovascular complications are multifactorial. This complications are caused by disorders of calcium - phosphate metabolism already at the beginning of patient's irreversible renal failure. The factors playing the most important part in the development o renal ostedystrophy and are hypocalcemia and increasing serum phosphate levels associated with a declining glomerulal filtration. Two main types of renal osteodystrophy can be described - high turnover bone disease and low turnover disease. High turnover forms of renal osteodystrophy are characterized by rapid bone turnover caused by abnormally high PTH levels. The two types of high turnover renal osteodystrophy are predominant hyperparathyroid bone disease, and mixed uremic osteodystrophy. Low turnover forms of renal osteodystrophy are characterized by a dramatic drop in the rate of bone remodeling, caused by oversuppression of PTH and/or by aluminum accumulation. The bones become thin and overly flexible, and bowing may occur. The two types of low turnover renal osteodystrophy are low turnover uremic osteodystrophy and aluminum-related bone disease. Patients who have end-stage renal disease with increased serum phosphate levels and calciumphosphate products are associated with an increased prevalence of ectopic...

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Bisphosphonates (BPs) are stable analogues of pyrophosphate widely used for the treatment of bone diseases characterised by increased bone resorption. Studies over the years have shown that the pharmacological potencies of BPs are dependent both on their binding affinities for bone mineral and on their inhibitory actions on osteoclasts. In addition, potential effects on other cell types present locally in the environment of skeletal tissues have been reported. The present study systematically evaluated the relative mineral-binding affinities of individual BPs of clinically relevance in mixtures of these compounds and the changes with elution pH by using column chromatography with ceramic hydroxyapatite and fluoroapatite combined with mass spectrometric identification and quantitation of the individual BPs. The results indicate that pH has a profound effect on the ionisation of the phosphonate and R2 functional groups, with BPs having greater affinities at lower pH as shown by increased retention times. Moreover, two other approaches, namely using Langmuir adsorption isotherms and competition assays based on fluorescent BP, have been developed to assess the mineral-binding capacities and dissociation constants of BPs. These results suggest that there are substantial differences among BPs in their binding to hydroxyapatite. From the cellular aspect of my study, I present evidence for the anti-apoptotic effects of BPs in osteocytes and osteoblasts. However, the study of prosurvival signalling pathways involved in these cells needs to be optimised. The work described in this thesis provides novel insights into the physiological and biological mechanisms of BP action. My project has provided a better knowledge of the physicochemical properties of BPs, which are highly relevant to their differential distributions within bone, their biological potencies, and their durations of action. Additionally, the cell culture studies may provide new information on the cellular effects of BPs on osteocytes and osteoblasts.

acase@tulane.edu / 1 / YD

Made available in DSpace on 2014-06-11T19:29:51Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-02-15Bitstream added on 2014-06-13T20:20:18Z : No. of bitstreams: 1 cangussu_lm_me_botfm.pdf: 560084 bytes, checksum: e6b5d6f4f10f581592da0884c164a71a (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Avaliar a associação entre o equilíbrio postural e a densidade mineral óssea (DMO) em mulheres na pós-menopausa e correlacionar com o risco de quedas. Realizou-se estudo de corte transversal com 225 mulheres, idade 45-75 anos, atendidas em Hospital Universitário. Incluíram-se mulheres em amenorréia >12 meses e idade ≥ 45 anos, com valores de DMO (coluna lombar e colo de fêmur) pelo DXA, dos últimos 12 meses. E se excluíram aquelas com doenças neurológicas ou musculoesqueléticas, história atual de vestibulopatias, déficit visual sem correção, obesidade grau III e usuárias de drogas que alterem o equilíbrio. As mulheres foram divididas segundo a DMO em > -2,0 DP (n=140) e ≤ -2 DP (n=85). Foram analisados o histórico de quedas (últimos 24 meses) e as características clínicas e antropométricas. O equilíbrio postural foi avaliado pela estabilometria (plataforma de força), teste de Romberg, alcance funcional e teste do agachamento. Para análise estatística foram empregados o Teste de Wilcoxon para variáveis quantitativas, o teste do Qui-Quadrado ou Exato de Fisher para variáveis categóricas e o método de regressão logística para o risco de quedas (Odds Ratio-OR). As pacientes com DMO > -2,0 DP eram mais jovens e com menor tempo de menopausa, assim como apresentavam maior IMC e circunferência da cintura quando comparadas aquelas com baixa DMO (≤ -2 DP) (p<0,05). Observou-se que 57,8% (130/225) das participantes relataram episódio de queda nos últimos dois anos, sem diferença significativa na distribuição percentual entre os grupos (p=0,055). Nos parâmetros estabilométricos e no alcance funcional não foram demonstradas diferenças na comparação entre os grupos (p>0,05). No teste de Romberg notou-se aumento progressivo da positividade à medida que aumentava a dificuldade do teste, sendo observada diferença significante entre os grupos apenas com... / To analyze the association between postural balance and bone mineral density (BMD) in postmenopausal women and correlate it with risk for falls. A cross-sectional study was conducted on 225 women aged 45-75 years and cared for at a University Hospital. Women in amenorrhea >12 months and age ≥ 45 years, with BMD values (lumbar spine and femur neck) by DXA for the last 12 months, were included. Those with neurological or musculoskeletal disorders, current history of vestibulopathies, uncorrected visual deficit, level-III obesity or drug use that could affect balance were excluded. The women were divided, according to BMD, in > -2.0 DP (n=140) and ≤ -2 DP (n=85). Histories of falls (last 24 months) as well as clinical and anthropometric characteristics were evaluated. Postural balance was assessed by stabilometry (strength platform), Romberg’s test, functional reach test and the crouching test. For statistical analysis, Wilcoxon’s test was used for quantitative variables, the Chi-square or Fisher’s exact test for categorical variables and the logistic regression method for fall risk (Odds Ratio-OR). Patients with BMD > -2.0 DP were younger and had been menopausal for a shorter period of time; they also showed higher BMI and larger waist circumference as compared to those with low BMD (≤ -2 DP) (p<0.05). It was observed that 57.8% (130/225) of the participants reported fall episodes in the last two years, without significant difference in the percent distribution between the groups (p=0.055). No differences were found in the comparison between the groups (p>0.05) for stabilometric parameters or functional reach test. Concerning Romberg’s test, progressive positive increase was observed as the test difficulty increased, and significant difference between the groups was found only when the women kept their feet in a series and their eyes closed (p<0.05). When evaluating the ... (Complete abstract click electronic access below)

Osteoporosis and osteopenia are long-term side effects of bone marrow transplant (BMT). The purpose of this study was to determine the prevalence of bone mineral density (BMD) abnormalities in pediatric patients prior to BMT. Forty-four pediatric patients were evaluated with DEXA scans. The average Z-score was -0.37. Thirty-six percent had abnormal BMD. Sixty-seven percent of ALL patients had abnormal BMD. Patients with non-malignant diseases were significantly more likely to have abnormal BMD. Patients with ALL had more defects than solid tumor patients. Females had more defects than males. These results demonstrate BMD defects are common in children prior to BMT, especially in patients with ALL.

Osteoporosis is caused by a multitude of factors. An individual’s risk for experiencing a bone fracture as a senior citizen increases without early intervention. Healthcare professionals do not have access to validated survey tools to identify young adults in need of osteoporosis prevention education, although survey tools to identify postmenopausal women at high risk for low bone mass are available. The purposes of this study were to evaluate three of these survey tools for use in a younger population, and to determine if young adults with osteoporosis risk factors received bone health education from a health professional. Forty-two men and 41 women completed surveys and health questionnaires; responses were compared to bone mineral density (BMD) and content (BMC) measurements. Healthcare professionals discussed bone health with only 13% of participants. Chi-square analysis revealed that health professionals were not more likely to discuss osteoporosis with subjects based on age or gender. Participants with T-scores ≤ -1.0 were not more likely to receive bone health education. Area under the receiving operating characteristic (AUROC) curves analysis revealed that no survey tools were able to identify moderate-risk participants at T-scores ≤ -1.0, and AUROC curves for all surveys did not exceed 0.525 at this level. Two surveys detected participants at high risk for bone disease with identical AUROC curves of 0.821 at a T-score ≤ -2.0, and 0.813 at a T-score ≤ -2.5. The AUROC curves indicate that current tools designed for older women do not detect young adults with moderately low T-scores. / Master of Science

Bone densitometry is the only clinically acceptable and objective method for the accurate measurement of bone mineral density (BMD), bone mass, and the prediction of bone fracture risk. Dual energy X-ray absorptiometry (DXA) is the primary diagnostic bone densitometry tool used in clinical settings. A growing need exists to determine how health care professionals and women use the information obtained from DXA scans in the management of osteoporosis. Few studies have investigated physicians' recommendations and women's compliance related to detection and treatment of osteoporosis after receiving BMD results by DXA. No studies have investigated actions that women have taken after receiving BMD test results conducted by DXA. This descriptive, exploratory study assessed actions that women took and what they perceived their physicians did after receiving BMD results. Using a telephone survey, actions of 138 women, who participated in a previous study of bone health, were evaluated regarding osteoporosis detection, prevention, and treatment. Many women (62%) shared their BMD test results with health professionals. However, 75% of women with low BMD status and who shared their results with health care professionals reported that they did not receive recommendations for advanced tests. Moreover, these women did not receive recommendations for dietary intake changes (60%), medication use (72%), or other lifestyle changes (60%). Yet 58% of these women self-initiated behavioral changes after receiving their BMD test results. Of the women who changed their behaviors, 67% of postmenopausal women increased exercise. Ninety-two percent of these women indicated they would engage in BMD testing again. / Master of Science

Osteoporosis is a condition involving decreased bone mineral density (BMD) and increased fragility of the skeletal system. Osteoporosis affects ~75 million individuals in the United States, Europe, and Japan. In the United States alone, hip fractures affect 500,000 individuals per year, and annual healthcare costs for osteoporotic fractures are approximately $14 billion. A high peak BMD can prevent or delay the onset of osteoporosis and its complications. Exercise and diet may affect peak BMD by as much as 20 to 40% each and have been identified as the two most important controllable factors determining BMD. The current study investigated the effect of a calcium, vitamin D, and vitamin K supplement combination during initial military cadet exercise training on: BMD, stress fracture occurrence, hormones associated with BMD, and biochemical markers of bone turnover. Significant changes in BMD, either between the supplemented group or the unsupplemented group or across time for both groups were not found. The majority of participants (n = 22) had unexpectedly high levels of physical activity prior to enrollment, and the initial military exercise training program included only moderate levels of activity. Therefore, the exercise stimulus to bone was likely insufficient to promote gains in BMD, regardless of the nutrient supplement status. Serum insulin-like growth factor-1 and osteocalcin significantly increased over time (p < 0.05 and p < 0.001, respectively), irrespective of treatment group. Significant decreases were found in dietary intake of calories (p < 0.01), carbohydrate (p < 0.05), protein (p < 0.0001), and fat (p < 0.01) over time. Decreases in reported dietary intake were likely due to less variety of foods eaten, and diminished compliance with food records. Significant differences were not found between groups or across time in dietary intakes of calcium, vitamin D, or vitamin K. Low dose supplementation with a calcium, vitamin D, vitamin K supplement during initial military training in young-adult cadets did not change BMD or alter stress fracture occurrence. / Master of Science

The dramatic rise in health care and economic costs as well as increases in morbidity and mortality related to lifestyle behaviors and non-communicable diseases have resulted in an increasing emphasis on research and intervention initiatives aimed at primary prevention. As there is growing evidence that the antecedents of adult diseases such as obesity and osteoporosis have roots in early childhood, physical activity interventions in early childhood (4 to 6 years of age), which has been identified as a critical period, may influence the development of fat and bone mass at this young age and have a potential impact on adolescent and young adult health status and thus improve population health. The intent of this study was to investigate the effects of structured physical activity, specifically early involvement in gymnastics, on early childhood body composition development.<P>Sixty three (25 male and 38 female) 4 to 6 year old children participating in gymnastics programs were compared to 95 control (49 male and 46 female) children. Anthropometric measurements included height, weight, BMI, waist circumference, and skinfold thickness. Dual energy x-ray absorptiometry (DXA) was used to measure whole body bone density and fat mass. Physical activity, physical inactivity, dietary intake, and birth weight of the participants as well as parental heights and weights were also obtained. <P>No significant differences were found, at any age, between the groups in height, weight, BMI, waist circumference, skinfold thickness, physical activity, physical inactivity, dietary intakes, and birth weight or in parental heights and weights (p>0.05). Additionally, there were no significant differences in fat and bone parameters once the confounders of age and size were controlled (p>0.05). <P>This investigation found that young children entering a gymnastics program did not differ in either bone mass or fat mass compared to controls. This was surprising as differences in these parameters have been found in adolescent gymnasts. Thus my results indicate that the potential effects of gymnastics training may have not yet manifested themselves. To answer this question longitudinal measures are required to ascertain whether the body composition differences observed in adolescent gymnasts are due to prolonged exposure to gymnastics involvement.