Dissertations / Theses on the topic 'Bone cancers in children and adolescents'

Introduction: Puberty is a crucial period for rapid changes in bone mineral, size, geometry, and microarchitecture. The mechanostat theory postulates that increased mechanical loading will affect bone phenotype and strength during development and in later life. Individuals with cystic fibrosis (CF) have an increased risk of developing osteoporosis and fragility fractures in young adulthood, which may be caused by poor growth. The aim was to investigate whether sex and disease status modified the relationship between: 1) puberty and bone, and 2) muscle and bone. This would contribute to the understanding of how sex (males vs. females) and disease group (CF vs.controls) alters the relationship between bone and muscle in children and adolescents as they transition through puberty and who, on a population level, differ in the prevalence of osteoporosis and risk of fracture in later life. Methods and Analyses: This observational study used novel imaging and muscle assessment techniques to measure bone and muscle parameters in White Caucasian children and adolescents, aged 8 to 16 years, living in the UK, with children with CF (n=65) and controls (n=151). Anthropometry and pubertal status were assessed. Dual energy X-ray absorptiometry, peripheral quantitative computed tomography (pQCT), high-resolution pQCT, and jumping mechanography were used to measure bone and muscle outcomes. ANCOVA with Scheffé post hoc and multiple linear regression tests were performed. Data were adjusted according to the research aims and included covariates; sex, disease group, pubertal stage, age, quadratic age, height, weight, maximum force (Fmax), and maximum power (Pmax). Data are presented as beta-coefficient (%) and p-value, with the significance level set to p < 0.05. Results: In height adjusted analyses, among healthy participants, females had smaller bones and lower bone density compared to males. With pubertal maturation, females had lower apparent gains in the distal and proximal total area (Tt.Ar and CSA), distal cortical porosity (Ct.Po) and proximal bone strength (SSI) but higher apparent gains in distal and proximal cortical bone density(Ct.BMD, Ct.TMD, vBMD). Females had consistently lower distal total area (total CSA) and density (total vBMD), distal trabecular density(BV/TV) and number(Tb.N), and proximal cortical area(CSA) compared to males, across all stages of puberty. With increasing muscle force (Fmax), females had higher apparent gains in total body less head bone mineral (TBLH BMC) and bone area(BA), distal total and trabecular density (total and trab vBMD) compared to males. In contrast, with increasing muscle power (Pmax), females had higher apparent gains in distal total and cortical densities (D100, Ct.BMD and Ct.TMD), and distal trabecular thickness (Tb.Th), and proximal cortical density (cortical vBMD) but lower apparent gains in distal cortical porosity (Ct.Po) and trabecular number (Tb.N) compared to males. In height adjusted analyses, participants with CF had smaller bones and lower bone density compared to controls. With increasing pubertal maturation, participants with CF had lower apparent gains in total body less head bone mineral and bone area, and in distal trabecular density, cortical porosity, and trabecular thickness compared to controls. Participants with CF had consistently lower distal total and cortical area, distal total and trabecular densities and proximal bone strength compared to controls, across all stages of puberty. With increasing muscle force, participants with CF had lower apparent gains in total body less head bone mineral and bone area, distal total density, trabecular density, and trabecular number. In contrast, with increasing muscle power (Pmax), participants with CF had higher apparent gains in distal trabecular density (BV/TV) and trabecular number (Tb.N) compared to controls. Conclusion: These findings suggests that sex and disease status do modify the relationships between puberty and bone, and between muscle function and bone. Skeletal adaptation to muscle differs between sexes and in populations with chronic disease, which may explain sex and disease group differences in risks of osteoporosis and fracture. Bone adaptation to muscle in children with CF is altered, which may lead to narrow, under-mineralised bones, with lower bone strength in later life. Understanding better impairments in muscle functions may provide targets for intervention to improve skeletal health in later life.

Background: Numerous studies have focused on the contribution of calcium and vitamin D to bone growth and mass accumulation, but not many focused on other nutrients such as vitamin for promoting bone growth and mineralization. Objectives: 1) To determine whether dietary intakes of Vitamin C positively supports bone growth and increases the bone mineral density in both boys and girls. 2) To determine the effectiveness of fruits and vegetables for improving bone mineral density in adolescents. Search Methods: The search strategies included a search on PubMed.gov for studies from year 2000 to present that focused on the correlation between the vitamin C or fruits and vegetable intakes and the bone development.

Introduction: Overweight children have greater bone mass than their healthy weight peers; however, they sustain more fractures. Thus, there is a need to better understand the relation between body fat and bone strength and aspects of bone quality such as bone microstructure that contribute to bone strength. Methods: I aimed to determine the cross-sectional relationship between fat mass (FM) and aspects of bone quality (strength, geometry, density and microstructure) at the distal radius and distal tibia in boys (n = 137, 15.6 ± 3.3 yrs on average) and girls (n = 157, 14.5 ± 3.9 yrs) in the context of the functional model of bone development (after adjusting for lean mass (LM)). FM and LM were measured using dual energy X-ray absorptiometry and bone quality was measured using high resolution-peripheral quantitative computed tomography. Results: In boys, FM negatively predicted bone strength at the radius but not at the tibia. Conversely, FM did not significantly predict bone strength in girls. In both boys and girls, FM negatively predicted total area at the radius but not the tibia. In girls but not boys, FM positively predicted cortical bone mineral density at the tibia but not the radius. For bone microstructure, FM did not significantly predict many variables; however, FM negatively predicted cortical thickness at the tibia in boys, trabecular thickness at the tibia in girls, and cortical porosity at both the radius and tibia in girls. In nearly all cases, LM mediated the relationship between FM and bone quality, whereby prior to adding LM to regression models FM positively predicted bone quality; however, after adjusting for LM the positive associations became non-significant or negative. Conclusions: The relation between fat and bone is complex and appears to be sex- and site-specific. My results also highlight the important influence of lean mass on bone strength. Longitudinal studies with larger cohorts and more overweight and obese participants would clarify the sex-specific muscle-fat-bone relationships during growth and into adulthood. The potentially hazardous influence of high levels of fat mass on child and youth bone health must be considered among the adverse consequences of overweight and obesity.

Childhood onset growth hormone deficiency (CO-GHD) may contribute to low bone mass and alterations to body composition. This thesis consists of a series of studies utilising dual-energy X-ray absorptiometry (DXA), peripheral quantitative computerized tomography (pQCT) and biochemical assessment of bone health and body composition of CO-GHD. In addition, metabolic profiles, glucose metabolism as well as quality of life have been studied in these subjects. Furthermore, an interventional study of weight bearing exercise (WBE) was performed to explore its role in influencing the bone health of children and adolescents with CO-GHD. Chapter 1, relevant literature reviews explore: bone structure, growth, development and strength; GH/IGF-1 system and its actions; CO-GHD and its impacts during childhood and transition; and WBE and its mechanism and impacts on bone health. Chapter 2 presents the rationale and specific aims of this thesis. Chapter 3, a retrospective multicentre review of management of young adults with CO-GHD in four paediatric centres in Scotland during transition. Medical records of 130 eligible CO-GHD adolescents (78 males), who attained final height between 2005-2013 were reviewed. Of the 130, 74/130(57%) had GH axis re-evaluation by stimulation tests /IGF-1 measurements. Of those, 61/74(82%) remained GHD with 51/74(69%) restarting adult rhGH. Predictors of persistent GHD included an organic hypothalamic-pituitary disorder and multiple pituitary hormone deficiencies (MPHD). Despite clinical guidelines, there was significant variation in the management of CO-GHD in young adulthood across Scotland. Chapter 4, a cross-sectional control study of bone DXA measurements in (n=21) subjects with CO-GHD treated with rhGH and had attained final height from 2005 to 2013 in a single tertiary paediatric centre compared to (n= 21) heights/age matched healthy controls. By applying different models of DXA adjustment, our analysis revealed lower TB-BMC for bone area in males with CO-GHD and lower LS-BMAD SDS in females with CO-GHD compared to matched controls. In addition, subjects with CO-GHD had lower LM for height and higher FM for height compared to controls, and this was more pronounced in males than females (p=0.04). The time of onset and aetiology of CO-GHD have a larger influence on accrual of bone mass in these patients. These findings indicate that adolescents with CO-GHD have a low bone mass, despite prior long term rhGH replacement therapy. In chapter 5, we investigated bone health of subjects with CO-GHD at time of initial evaluation and retesting at final height. A total of 25 children (first time assessment group) undergoing GH stimulation tests for investigation of short stature (naive GHD-15, normal-10), and 11adolescents with CO-GHD (retesting group) undergoing biochemical re-evaluation at final height after withdrawal of rhGH therapy (persistent GHD-7, GH-sufficient-4) were recruited from Royal Hospital for Children between 2012-2013. By using further bone health assessment methods in addition to DXA (including p.QCT, mechanography, bone profiles and biomarkers), the bone density and body composition did not differ when we compared GHD to matched height but normal GH at initial evaluation and retesting. However, naive GHD had lower muscle force as assessed by mechanography compared to the normal. In addition, bone resorption biomarker CTX was significantly higher in naive GHD vs. normal and that was significantly correlated to PTH levels in both first time assessment and retesting groups. Our results suggest that muscle force and serum PTH may be important determinants of bone health in subjects with CO-GHD. Chapter 6 investigates lipids, adipokines (leptin- adiponectin- resistin) and glucose homeostasis and their relationship with bone and body composition in children and adolescents with CO-GHD at times of initial evaluation and retesting at final height (same population as chapter 5). Lipid profiles, adipokines and glucose homeostasis were not different between those with GHD and those who had normal GH levels across the groups of first time assessment and retesting. In the retesting group, those who were older at the time of diagnosis of CO-GHD with a shorter duration of rhGH therapy were more likely to have higher cholesterol(r=0.9, p<0.001), leptin (r=0.8, p<0.001), and lower osteoclacin (r=-0.7, p=0.01) at final height. Leptin levels correlated positively with osteocalcin at diagnosis (r=0.51, p=0.01) but inversely at retesting (r=-0.91, p<0.01). The conclusion was that the timing and duration of childhood rhGH therapy might influence adiposity parameters and bone metabolism in subjects with CO-GHD. In chapter 7 the study participants of chapter 5 were asked to complete either Short Form-36 (SF-36) or Adult Growth Hormone Deficiency Assessment (AGHDA) quality of life (QoL) questionnaires at the time of assessment of their GH axis. Our analysis showed that the overall QoL was not altered in children with naive GHD with a total score of SF-36 [93 (77, 96) naive GHD vs. 90 (84, 93) normal, P=0.56] (higher scores reflect better QoL). However, naive GHD had less energy and vitality scores compared with normal (75 (65, 100) vs. 95 (65,100) respectively, p=0.04), when the normal scored lower in the subscale of emotional well-being compared to those with naive GHD (78 (55, 84) vs. 90 (68, 96) respectively, p<0.001). In the retesting group, those with persistent GHD scored better in the AGHDA than GH sufficient (6 points (2, 8) vs. 9 points (7, 17) respectively, though not significant (p= 0.10) (higher scores reflect poorer QoL). Unexpectedly, subscale analysis showed that GH-sufficient subjects significantly lacked energy and complained of tiredness compared to those who were confirmed to have persistent GHD (5 points (3, 6) vs. 1 point (0, 1) respectively, p= 0.03). Further studies to validate QoL specific instruments in this population are needed with greater insight to elucidate factors that modify the relationship between GH status and QoL in children and adolescents. Chapter 8 was a prospective intervention, randomised controlled study of 14 subjects among the first time assessment group (GHD-10, normal-4) and five subjects with CO-GHD among retesting group (persistent GHD-4, GH-sufficent-1). Subjects were randomised into either an exercise intervention group (EX) (25 jumps off 25 cm platform step/three days/week for six months) or a control, in addition to rhGH being prescribed. The results of this study were limited by the small sample size and poor compliance. Therefore, there were insufficient data to recommend the use of weight bearing exercise in the absence of rhGH in children and adolescents with CO-GHD. Further studies with adequate sample size that can more rigorously exam the optimal exercise interventions are needed. Chapter 9 discusses the main findings of each chapter in this thesis and outlines potential limitations of the thesis methodology, and some important and interesting areas for future research in children and adolescents with CO-GHD.

Thalassaemia and sickle cell disease (SCD) are the most widely distributed blood genetic disorders that occur at a high frequency in some populations including the Mediterranean region, parts of the Middle East, South East Asia and the Indian subcontinent. It is estimated that thalassaemia major affects 100,000 newborn every year world-wide. The high incidence of these chronic haemolytic diseases in developing countries poses a high load on the national economy because of the expensive treatment protocols and the considerably high morbidity rates of these patients. Repeated blood transfusion to keep haemoglobin above an acceptable level requires well-equipped blood banks with expensive facilities to screen, store and manipulate blood and blood products. Iron chelation therapy is an essential part of treatment to avoid or delay the deleterious effects of iron overload on different organs including the liver, heart, pancreas and endocrine glands. This inquires injecting deferoxamine subcutaneously for 12 hours daily with a special pump. Both deferoxamine and pumps are expensive and therefore not accessible for all patients. In developing countries, the majority of transfusion-dependent patients with chronic haemolytic anaemia (thalassaemia and SCD) suffer from the consequences of sub-optimal treatment. The mortality rate is still high and usually patients die before the age of 30 years. They also suffer from chronic multi-organ damage including cardiac failure, liver cirrhosis, insulin-dependent diabetes mellitus, growth and pubertal failure and many skeletal abnormalities and fractures. In developed countries the introduction of high transfusion regimes and efficient chelation therapy improved survival rates and prevented cardiac and hepatic damage. However, a majority of thalassaemic patients still have significant growth and pubertal abnormalities, bone disease and multiple endocrine disorders. In Egypt the incidence of thalassaemia major ranges between 0.1 - 0.2% which gives very high patient load on the medical services. In our University of Alexandria Children's Hospital, Alexandria, Egypt. The Haematology clinic has an average of 150 thalassaemic children registered. The same problem is encountered by me in the Royal Hospital, Muscat, Oman, with high prevalence of SCD and thalassaemia and suboptimal treatment. Because of the restricted economic resources, both hospitals adopt a low transfusion therapy (to keep haemoglobin above 9 g/dl) with IM chelation 3 times per week. With this form of sub-optimal treatment we observed that a large number of our thalassaemic children have severe growth and pubertal failure/delay, beside other hepatic, cardiac and skeletal abnormalities. In fact they constitute 40% of patients attending our Endocrinology clinic. This stimulated me to perform an extensive study to survey growth and pubertal development in theses patients (study-1) and investigate the different factors that might affect their growth and pubertal development (studies 4 through 10) a \veU as bone mass density (studies > 1,12). The frequent involvement of the liver in these patients led us to study some hepatic functions and the prevalence of transfusion-associated hepatitis B surface antigenaemia and hepatitis-C virus antibody scropositivity in relation to their linear growth (studies 2,3). We studied the nutritional intake of these patients, their intestinal absorption of D-Xylosc and 48-h stool fat content in relation to their body mass index, subcutaneous 'at thickness and mid-arm circumference (studies 4,5,9). Their defective linear growth urged us to investigate their growth hormone (GH) secretion (spontaneous nocturnal as well as after provocation) and insulin-like growth factor-I (IGF-I) and IGK-binding protein-3 (IGKBl'3) concentrations. Our findings demonstrated high prevalence of defective GH secretion in these children that necessitated imaging of their hypothalamic pituitary area. Imaging studies revealed original data about structural abnormalities in the anterior pituitary gland, different degrees of pituitary atrophy and empty sella and infiltration the gland as well as the mid-brain by hacniosidrin in thalassaemic children, the mechanism of these findings was explained (studies 4-6,10). Because of their slow growth, the presence of abnormal GH/IGF-I/BP3 axis, and structural abnormalities of the pituitary gland, the next step dealt with the response of IGF-I to exogenous GH and the clinical response of their linear growth to GH therapy for a year or more (studies 4,9). Based on the fact that these patients have high prevalence of bone pains and osteoporosis during late childhood and have high risk of spontaneous fracture thereafter, we measured their bone mass density to investigate the relation between the former and the degree of iron load, growth parameters, and different anabolic hormone concentrations in these patients (studies 11,12).

Introduction: Little is known about the aetiology of cancer in teenagers and young adults (TYA) aged 15-24 years, although in England, cancer is the most common cause of disease-related mortality in this age group. The most common cancers at this age are lymphomas, central nervous system (CNS) tumours and germ cell tumours (GCT). The commonest carcinomas seen at older ages including lung, breast, large bowel and prostate account for only 3-4% of TYA cancers. In this thesis I describe the incidence patterns of selected cancers in TYA and the variation seen with geography, time and in population subgroups. The focus is on CNS tumours, GCT and bone tumours as they either peak in incidence in TYA and/or contribute disproportionately to cancer related mortality in TYA. This will allow formulation of hypotheses regarding aetiology of cancer in this age group which can then be tested by further research. Methods: For the majority of the analysis, anonymised national cancer registration data from England on individual patients of all ages with newly diagnosed cancer between 1979 and 2003 were used. To contrast the incidence patterns in England with that of India, data from five Indian urban population based cancer registries were used for part of the analysis. Age, sex, site and histology specific incidence rates were calculated and expressed per million person years. All rates, where appropriate, were adjusted to the world standard population using direct methods. To explore the link of growth with development of osteosarcoma and Ewing sarcoma, a random-effects meta-analysis was undertaken on studies which investigated an association of these tumours with height at diagnosis. Results: The incidence of cancer in TYA overall in England exceeded that of India. This was also true for most individual sites including epithelial cancers of lung, colon/rectum, breast, ovary and cervix, and non-epithelial cancers including melanoma, Hodgkin lymphoma and testicular cancer. Notable exceptions to this pattern were cancers of the mouth, gall bladder and stomach (females only) where incidence was higher in India. In England, CNS tumours in TYA were a composite of pilocytic astrocytomas and embryonal tumours (representing tail end of childhood CNS tumours), pituitary tumours, nerve sheath tumours, high grade astrocytomas and meningiomas (representing early-onset of CNS tumours that peak in incidence in the 6th and 7th decade of life), and of CNS GCTs, pleomorphic xanthoastrocytomas and neurocytomas which show a peak incidence in TYA. Irrespective of site or histology, GCT in England showed a peak in incidence between ages of 10 to 39 years which was more marked in males. This however varied by site and the peak incidence was seen at 10 to 14 years in the CNS, 15 to 19 years in ovary, 25 to 29 in mediastinum & thorax and abdomen & pelvis, and 30 to 34 years in testicular tumours. Osteosarcoma and Ewing sarcoma were the predominant bone tumours in TYA in England and showed a distinct peak of incidence at 10 to 14 years age in females and a larger peak at 15 to 19 years age in males. The peak incidence of osteosarcoma of long bones of the lower limb was six times more than that at any other site while the peak incidence of Ewing sarcomas located in the bones of the central axis exceeded those in long bones of the lower limb. The average height of patients with osteosarcoma at diagnosis was found to be significantly above the average height of the reference population, at the 95% level. The association of greater height at diagnosis with Ewing sarcoma was also significant at the 95% level but much weaker. Conclusion: In this thesis I have explored the epidemiology of cancer in TYA using some of the established methodologies which have previously been used in advancing our knowledge of childhood and older adult cancers. These studies provide some clues to aetiology. Variation in environmental exposures and lifestyle factors between England and India can explain the majority of the differences in incidence patterns observed. Genetic predisposition to cancer along with carcinogen exposure could lead to early onset of some cancers generally seen in older adults. Regardless of site, the similarity in age-incidence patterns of GCT, suggests a common initiation of these tumours in embryonic/foetal life with variable rates of tumour progression as a result of local factors or events during postnatal and pubertal period. The incidence patterns of osteosarcoma along with the strong and consistent association with a greater height at diagnosis indicate that bone growth is important in the development of this tumour while different biological pathways which may be unrelated to growth could also be relevant for Ewing sarcoma.

O tecido adiposo e ósseo tem uma íntima relação, desde a origem comum nas células tronco estromais derivadas da medula óssea. Sabe-se que o peso corporal tem estreita correlação com a massa óssea em seres humanos. Porém, ainda não é claro qual componente do peso corporal tem maior influência sobre o ganho de massa óssea e sobre a adiposidade na medula óssea, visto que tanto indivíduos com baixo peso, quanto os obesos, apresentam altas taxas de fraturas. O objetivo deste trabalho foi comparar crianças e adolescentes obesos e eutróficos em relação a composição óssea, adiposidade da medula óssea em coluna lombar (L3), expressão do Receptor tipo 1 de IGF (IGF1R) e concentrações séricas de IGF-I e buscar correlação entre estas variáveis. Para tanto foram avaliados crianças e adolescentes de 10 a 17 anos, divididos em grupo controle e grupo obeso. Esses grupos foram submetidos a avaliação antropométrica, densitometria óssea de coluna lombar e corpo total e ressonância magnética de coluna lombar e abdome total, além de dosagens séricas de parâmetros bioquímicos e hormonais. Os pacientes do grupo obeso apresentaram associação positiva da densidade mineral óssea tanto com massa gorda quanto com massa magra, enquanto que o grupo controle apresentou associação positiva da densidade mineral óssea apenas com a massa gorda. Não houve diferença entre os grupos quanto a adiposidade da medula óssea, nem quanto aos valores de IGF-I, IGFBP3 e expressão do gene do IGF1R.
The adipose and bone tissue has an intimate relationship, from the common origin in stromal stem cells derived from the bone marrow. It is known that body weight has a close correlation with bone mass in humans. However, it is still unclear which component of body weight has a greater influence on bone mass gain and adiposity in the bone marrow, since both individuals with low weight and obese have high fracture rates. The objective of this study was to compare obese and eutrophic children and adolescents in relation to bone composition, bone marrow adiposity in the lumbar spine (L3), expression of IGF type 1 receptor (IGF1R) and serum concentrations of IGF-I and to seek correlation between these variables. For this, children and adolescents between 10 and 17 years old were divided into control and obese groups. These groups were submitted to anthropometric evaluation, bone densitometry of the lumbar spine and total body and lumbar spine and total abdominal magnetic resonance, in addition to serum levels of biochemical and hormonal parameters. The patients in the obese group had a positive association of bone mineral density with both fat mass and lean mass while the control group showed a positive association of bone mineral density with fat mass only. There was no difference between the groups regarding bone marrow adiposity, nor regarding IGF-I, IGFBP3 and IGF1R gene expression.

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Diabetes Mellitus (DM) and osteoposes are chronic diseases with great socioeconomic consequences, mainly due to the late complications and consequent disabilities. The potential effects of DM on bone metabolism remain a very conroversial issue, and disagreement exists with regard to the clinical implications of diabetic osteopenia and the mechanism of its ocurrence. The issue is further complicated by the contribuicion of the especific factors, such as duration of disease an dthe degree of metabolic control. The objective of this study is to identify the osteopathy in children and adolescents with DM 1 assisted in the hospital of pediatrics, UFRN, through biochemical markers of bone and mineral metabolism and the extent of bone mineral density. The study was composed by 74 diabetics type 1 patients (DM1) of both gender and aged 6 to 20 yars. Normoglic?mic group was composed by 97 healthy subjects of both genders, which showed the same age range of DM1, in addition to same socioeconomic class. These individuals qere students from the networks of public education in the city of Natal-RN, randomly invited to paticipate in our study. Both groups DM1 and NG were divided intofour subgroups, according to the classification of tanner , T1, T2, T3, T4 for achieving a benchmark. Diabetic individuals showed up with a poor glycemic control. the group DN1 T4 showed an incresead value for total protein, albumin, urea and microalbumiuria are predictors of grumelura injury in DM1 patients . The total alkaline phosphatase activitywas kept on high levels for both groups because they are in a stature development age. For osteocalcin there were decreased levels for groups Dm1 T1, T2, and T3 when compared to their NG (s), suggesting that this decrease could be associated with reduction in the number and/or differentiation os osteoblasts thereby contributing to reducing bone formation. There were no changes in the activity of TRAP. The serum concentrations of total and ionized calcium, phosphorus and magnesium were included within the RV. It was observed that the BMD (Z- SCORE ) has always been within the RV for both groups, despite to DM1 T4. Taking all together, our results support the hypothesis that children and adolescents with type 1 DM present the risk in the long run to suffer a reduction in the bone mass, associated to poor glicemic control and disease duration. It could limit the bone growth and increase the probality of development of osteopenia, as well as other complications surch as retinopathy and renal failure
Diabetes mellitus (DM) a osteoporose s?o doen?as cr?nicas com grandes consequ?ncias socioecon?micas, sobretudo devido ? complica??es tardias e consequente desabilidades. Os efeitos potenciais do DM no metabolismo ?sseo continua a ser uma quest?o controversa, e ainda n?o existe um consenso no que diz respeito ?s implica??es cl?nicas da osteopenia diab?tica e os mecanismos da sua ocorr?ncia. Entretanto, a contribui??o de fatores espec?ficos, tais como a dura??o da doen?a e o grau de controle metab?lico tem sido muito discutidos. O objetivo do presente estudo foi identificar precocemente a osteopatia diab?tica em crian?as e adolescentes com DM 1 atendidos no Hospital de Pediatria da UFRN atrav?s de marcadores bioqu?micos do metabolismo mineral e ?sseo, marcadores da fun??o renal e da medida da densidade mineral ?ssea (DXA; Z-score L1-L4) . O estudo foi constitu?do por uma amostra de 74 pacientes diab?ticos tipo 1 (DM1) de ambos os sexos, com faixa et?ria entre 6 a 20 anos. O grupo normoglic?mico (NG) foi constitu?do por 97 indiv?duos saud?veis, de ambos os sexos, os quais apresentaram a mesma faixa et?ria do DM1, al?m de compreenderem a mesma classe socioecon?mica. Estes indiv?duos eram alunos de escolas da rede p?blica de ensino da cidade de Natal-RN, convidados aleatoriamente a participar do nosso estudo. Tanto o grupo DM1 quanto o NG foram divididos em quatro subgrupos, de acordo com a Classifica??o de Tanner, T1, T2, T3, T4, para viabilizar uma avalia??o comparativa. Os indiv?duos diab?ticos apresentaram um controle glic?mico insatisfat?rio, com valores de glicemia e HbA1C significativamente superiores aos obtidos para os NG. O grupo DM1 T4 apresentou valores aumentados de prote?nas totais, albumina, ur?ia e microalbumin?ria, sugerindo assim um in?cio de comprometimento renal, visto que os valores elevados de microalbumin?ria s?o preditores de les?o glomerular em pacientes DM1. A atividade da fosfatase alcalina total mostrou-se acima dos VR nos grupos DM1 e NG por estes estarem numa faixa et?ria de desenvolvimento estatural. Observa-se uma diminui??o da concentra??o de osteocalcina para os grupos DM1 T1, T2 e T3 quando comparados aos respectivos NG (s), sugerindo que esta diminui??o estaria associada a diminui??o do n?mero e/ou da diferencia??o dos osteoblastos no seu est?gio final de matura??o, contribuindo consequentemente para a redu??o da forma??o ?ssea. N?o foram observadas altera??es na atividade da TRAP. As concentra??es s?ricas de c?lcio total e ionizado, f?sforo e magn?sio estavam compreendidos dentro dos VR, mas os grupos diab?ticos apresentaram hipozincemia e hiperzinc?ria. A DMO (Z-score L1-L4; DXA) esteve sempre dentro dos VR para os grupos estudados, entretanto os grupos DM1 apresentaram sempre valores abaixo do seu respectivo NG, alca?ando uma diferen?a significativa para DM1 T4. O conjunto de resultados obtidos indicam que o baixo controle glic?mico e o tempo de doen?a representaram fatores de risco importantes para o desenvolvimento precoce da osteopenia diab?tica, bem como para o comprometimento renal e sinais de retinopatia.

Childhood and adolescence are time periods characterised by the rapid growth and development of the skeletal system. The timing and magnitude of skeletal development varies considerably between individuals however, environmental factors may make significant contributions to the variance in bone mass. To optimise the development of bone it is important to identify and promote factors that may have a positive effect on bone mass accrual. Two lifestyle factors that may enhance bone mass accural are calcium and exercise. The focus of this thesis was to investigate bone mass accural in children and adolescents and to determine the effect calcium and exercise have on bone mass accural.

Objective: To synthesise the best available evidence for the diagnostic test accuracy of measurement of serum procalcitonin compared to serum C-reactive protein for suspected osteomyelitis and septic arthritis in hospitalised children and adolescents. Introduction: Measurement of serum C-reactive protein remains a routine investigation for the diagnosis of osteoarticular infection in children and adolescents. Measurement of serum procalcitonin has been shown to outperform C-reactive protein in adults with osteomyelitis and septic arthritis. Before procalcitonin can be considered as a potential replacement or additional test in children and adolescents, a systematic review and meta-analysis targeting this population is needed. Inclusion criteria: Original studies reporting on the diagnostic accuracy of procalcitonin and/or C-reactive protein in children and adolescents aged between one month and 18 years admitted to hospital with suspected osteoarticular infection were included, compared to at least one reference test. The reference test was defined as positive culture or polymerase chain reaction confirmation of a pathogen from blood and/or bone biopsy and/or joint fluid aspirate and/or at least two of the following: 1) purulent material from sterile site; 2) positive radiological findings consistent with osteoarticular infection; 3) symptoms and signs consistent with osteomyelitis and/or septic arthritis. Methods: JBI methodology for systematic reviews of diagnostic test accuracy was employed. Information was sourced from four databases; MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Web of Science and four grey literature sources; Mednar, OpenGrey, Google scholar and ProQuest Dissertations and Thesis. Only studies published in English were considered. The methodological quality of selected studies was formally evaluated and sensitivity and specificity data were extracted and 95% confidence intervals determined. Meta-analysis was performed to estimate summary points using a bivariate model and generate a hierarchial summary receiver operating characteristic curve (HSROC) with global measures of test accuracy performance including likelihood ratio and diagnostic odds ratio. A narrative summary was provided where meta-analysis was not feasible. Results: Eight out of 3086 studies were included in the final analysis. Four of these studies used a common CRP test threshold of 20mg/L for septic arthritis cases only. At this threshold the estimated pooled sensitivity of C-reactive protein was 0.86 (0.68-0.96) and the pooled specificity 0.9 (0.83-0.94). Using a HSROC model from six studies including all osteoarticular infections, the diagnostic odds ratio for C-reactive protein was estimated to be 39.4 (14.8-104.9) with a positive likelihood ratio 5.3 (2.3-11.9) and negative likelihood ratio 0.1 (0.07-0.2). There were insufficient studies from this review to statistically evaluate the diagnostic accuracy performance of procalcitonin using meta-analysis. Conclusion: We have synthesised the best available evidence to evaluate the diagnostic test accuracy of serum measurement of procalcitonin and C-reactive protein in children and adolescents with suspected osteomyelitis and septic arthritis. Clinicians should continue to measure serum C-reactive protein as the preferred inflammatory marker in this setting and await more evidence before incorporating procalcitonin routinely into their diagnostic test strategy for this specific setting.
Thesis (MClinSc) -- University of Adelaide, School of Public Health, 2020

Índices reduzidos de Qualidade de Vida Relacionada com Saúde (QVRS) durante a adolescência têm sido associados a um estado de saúde menos apto na idade adulta, a um maior envolvimento em comportamentos de risco e a um estilo de vida sedentário. Este estudo tem como objetivo geral perceber se a Atividade Física (AF) e a Maturação estão associadas à perceção de QVRS (medida pelo KIDSCREEN-52) em 751 crianças, 395 rapazes e 356 raparigas, com idades entre os 11 e os 17 anos de idade. Esta investigação explora ainda a influencia que a idade cronológica, a idade óssea e o volume de AF podem ter nesta possível associação. Os resultados sugerem que: 1) O índice geral de QVRS é independente da idade cronológica, do nível de maturidade e da AF; 2) A dimensão “Saúde e Atividade Física” parece ser influenciada pelo nível de AF e pelo estado maturcional em ambos os géneros; 3) A dimensão “Estado de Humor Global” foi influenciada pelo estado maturacional, nas raparigas. Conclui-se que a maturação e a atividade física não influenciam o índice geral da QVRS. No entanto, a dimensão “Saúde e Atividade Física” parece ser influenciada pelo grupo de AF a que as crianças e adolescentes pertencem, em ambos os géneros; e a maturação parece ser particularmente importante na perceção desta dimensão por parte das raparigas.
Reduced rates of Health Related Quality of Life (HRQoL) during adolescence have been associated to a state of health less apt in adulthood, to a greater involvement in risk behaviors and to a sedentary lifestyle. This study’s general objective is to realize if the Physical Activity and Maturation are associated with the perception of HRQoL (measured by KIDSCREEN-52) in 751 children, 395 boys and 356 girls, aged between 11 and 17 years old. This research also explores the influence that chronological age, bone age and volume of Physical Activity may have on this possible association. The results suggest that: 1) The general index of the HRQoL is independent of chronological age, level of maturity and physical activity; 2) The dimension “Physical Well-being” seems to be influenced by the physical activity levels and by the maturational state in both genders; 3) The dimensions “Moods and Emotions” is influenced by maturational state, in girls. In conclusion, maturation and physical activity do not influence the overall index of HRQoL. However the dimension “Physical Well-being” seems to be influenced by the physical activity group to which children and adolescents belong, in both genders; and maturation seems to be particularly important in the perception of this dimension for girls.