Thesis (Ph.D.)--University of the Witwatersrand, Faculty of Health Sciences, 2012 / Osteoporosis has been described as a paediatric disease with geriatric consequences. This thesis explored the associations between proximal, historical and predictive genetic and environmental factors affecting bone mass and bone size in socio-economically- and environmentally-disadvantaged black and -advantaged white pre- and early-pubertal South African children. Data were collected from 476 children (182 black boys, 72 white boys, 158 black girls, 64 white girls) of mean age 10.6 years (range: 10.0-10.9), 406 biological mothers and 100 biological fathers. The main findings were that black children and their parents compared to white, had greater DXA-measured BMC at the femoral neck regardless of the way in which BMC was corrected for size (height, weight, BA and/or BAPC) and greater bone strength. Lumbar spine BMC was greater or similar depending on which measures were used to correct BMC for size. At the whole body, mid radius and distal one third of the radius, BMC varied between children, and between their parents, and were dependent on which measures were used to correct BMC for size. Weight at 1 year (WT1), length at 1 year (LT1) and birth weight (BW), were significant predictors of BMC of the femoral neck (P<0.05-0.01) after correcting BA and BMC for race/ethnicity, gender, age, socioeconomic status, bone age, height and weight at 10 years. Maternal and paternal heritability was estimated to each be ~30% in both black and white subjects. The main conclusion was that ethnicity is the single most important proximal factor affecting bone mass and bone size in 10 year old South African children. Black children demonstrate a superior bone mass and bone strength at the femoral neck. Historical and predictive factors however indicate that black children have not been programmed for optimal bone health in utero and early life, nor are contemporary environmental factors favourable for the maximisation of peak bone mass. This cohort may be at risk of developing osteoporosis as an elderly population, particularly at the lumbar spine and forearm.

PhD - Science / The study of the human metatarsals reveals frequent morphological variations from the typical descriptions. Pathologies of these bones in contemporary humans are common, and it has been suggested that some of these may be associated with some of these variants. Within this context, it was not clear to what extent footwear and other environmental factors such as modern substrates have influenced metatarsal morphology. This study essentially consists of three parts. First a preliminary morphometric study of the first, second and fifth metatarsals, to demonstrate the broad patterns of discrimination between selected hominoidea, namely humans, gorillas, chimpanzees and orangutans. In addition, the SKX 5017 first metatarsal fossil thought to be of Paranthropus robustus was included. Second, a primary morphometric investigation into the patterns of morphological discrimination in the five metatarsals of selected humans from South Africa, namely Sotho, Zulu, European and pre-pastoral subgroups. The contemporary human subgroups are associated with modern lifestyles and the pre-pastoral individuals represent habitually unshod forager societies from the western and southern Cape, dated 9750 - 2000 B.P. Third, a non-metric investigation into the patterns of variation in epigenetic and pathological variants of the metatarsus of the four human subgroups. A suite of existing metrical data was utilized for the preliminary hominoid study, and a suite of metrical and non-metrical data was collected for the primary human study from appropriate skeletal collections. Univariate analysis of these iv samples revealed important, though simplistic trends in morphology. Subsequent multivariate analyses utilizing principal components and canonical variates analysis were undertaken. Multivariate analysis of the hominoid samples revealed large scale variation between the species. This discrimination was on the basis of genetics, locomotor function and geography. Multivariate analysis of the human metrical data revealed very subtle morphological discrimination within and between the subgroups. Most of this discrimination appears to be genetic, followed by a functional or life-style based discrimination suggesting a broad discrimination between recent humans and the habitually unshod pre-pastoral subgroup. The epigenetic traits reveal considerable variation within groups, with similar trends between them. All subgroups have an appreciable number of identifiable pathological changes, with the recent human subgroups having the most and the prepastoral subgroup the least. In all subgroups, the hallucal metatarsal displays by far the greatest frequency in osseous modification. The main conclusions of this study are: 1.) The general patterns of morphological discrimination between the metatarsals of the human subgroups are very subtle. The non-metric traits are very variable, but do not discriminate between any of the subgroups. 2.) Both recent and ancient human groups present with similar patterns of pathological changes, but the frequency is different, these changes are to a great extent influenced by lifestyle. Regardless of temporal context, no clear correlation between morphological variation and pathological changes could be found.

Aims: 1) To determine the incidence or rates of fractures, the common sites of fractures, the causes of fractures and grades of trauma causing fractures in urban South African children of different ethnic groups from birth until 17/18 years of age. 2) To investigate the association between fracture prevalence, bone mass and physical activity in South African children. 3) To assess associations of fracture prevalence and bone mass in adolescents with maternal fracture history and bone mass and sibling fracture history. Design: Using the Birth to Twenty longitudinal cohort of children, we obtained retrospective information on fractures and their sites from birth to 14.9 years of age on 2031 participants. The ethnic breakdown of the children was black (B) 78%, white (W) 9%, mixed ancestry (MA) 10.5% and Indian (I) 1.5%. Using the Bone Health cohort of the Birth to Twenty longitudinal study, we retrospectively obtained information of lifetime fractures until age 14.9 years in 533 subjects. Bone mass (measured by DXA), anthropometric data, physical activity scores and skeletal maturity were obtained at age 10 and 15 years. Comparisons were made between those who did and did not fracture within the same sex and ethnic groups. The third component of the thesis utilized data from 1389 adolescent-biological mother pairs of the Birth to Twenty (Bt20) longitudinal study. Questionnaires were completed on adolescent fractures until 17/18 years of age and on sibling fractures. Biological mothers completed questionnaires on their own fractures prior to the age of 18 years. Anthropometric and bone mass data on adolescent-biological mother pairs were collected. Results: Twenty two percent of children had sustained a fracture one or more times during the first 15 years of life (males 27.5% and females 16.3%; p<0.001). The percentage of children fracturing differed between the ethnic groups (W 41.5%, B 19%, MA 21%, I 30%; p<0.001). Of the children reporting fractures, 20% sustained multiple fractures. The most common site of fracture was the upper limb (57%). In the second component of the thesis, white males who fractured were found to be significantly taller (10 years p < 0.05), more physically active (15 years p < 0.01) and had higher lean body mass (10 years p=0.001; 15 years p<0.05) than those who did not fracture; while white females, who fractured, were fatter (10 and 15 years p< 0.05), than their nonfracturing peers. White males who fractured had greater BA (bone area) and BMC (bone mineral content) at most sites at 10 and 15 years; BA and BMC were no different between fracturing and non-fracturing children in the other ethnic groups. No anthropometric or bone mass differences were found between black children with or without fractures. The third component of the thesis showed that an adolescent’s risk of lifetime fracture decreased with increasing maternal lumbar spine (LS) BMC (24% reduction in fracture risk for every unit increase in maternal LS BMC Z-score) and increased if they were white, male or had a sibling with a history of fracture. Adolescent height, weight, male gender, maternal BA and BMC, and white ethnicity were positive predictors of adolescent bone mass. White adolescents and their mothers had a higher fracture prevalence (adolescents: 42%, mothers: 31%) compared to the black (adolescents: 20%, mothers: 6%) and mixed ancestry (adolescents: 20%, mothers: 16%) groups. Conclusion: More than twice as many South African white children fracture compared to black and mixed ancestry children. This is the first study to show ethnic differences in fracture rates among children; a pattern that is similar to that found in South African postmenopausal women. The factor associated with fractures in white boys appears to be participation in sports activities, while in white girls obesity appears to play a role. We were unable to find any factors that could explain fractures in black children. Unlike the findings of some other studies, fractures in these children were not associated with lower bone mass or reduced skeletal size. Maternal bone mass also appears to play a role in determining fracture incidence in children, as the mother’s bone mass has a significant inverse association with their off-springs’ fracture risk throughout childhood and adolescence. Furthermore, there is a strong familial component in fracture risk among South African adolescents and their siblings, as evidenced by the increased risk of fracture in siblings of index children who have fractured during childhood and adolescence. Differences in fracture rates and bone mass between families and individuals of different ethnic origins may be due to differing lifestyles and/or genetic backgrounds.

A thesis submitted to the Faculty of Science, University of the Witwatersrand, Johannesburg, in fulfilment of the requirements for the degree of Doctor of Philosophy. 25th of July 2013, Johannesburg. / The cave deposits at Malapa, on the Malapa Nature Reserve, Cradle of Humankind World Heritage Site, Gauteng Province, South Africa, have yielded the remains of two extremely well-preserved hominins (Australopithecus sediba) and associated fauna, dated by U/Pb methods and palaeomagnetism to 1.977-1.8 Ma. The state of preservation of the hominins and some of the non-hominin material, characterised by complete and near complete elements, antimeric sets of bones, specimens in articulation, and well-preserved bone surfaces, is remarkable in the context of Plio-Pleistocene fossil assemblages accumulated in caves, and indicates a unique combination of taphonomic processes, not yet observed in contemporaneous cave deposits in the region. A comprehensive approach, including palaeontological, physical, and spatial analyses of the hominins and associated fauna was undertaken to determine, describe and interpret the taphonomy of the faunal material, with particular reference to the holotype and paratype of Au. sediba, Malapa Hominin 1 (MH1) and Malapa Hominin 2 (MH2). An innovative combination of Computed-Tomography (CT), micro-CT scanning and virtual reconstruction techniques was applied to create a 3D model of a selected area of the Malapa cave, with renderings of the two near-complete Au. sediba skeletons. The original burial position of the hominins was reconstructed, which necessitated the refitting of ex situ fossils into in situ deposits. The spatial distribution and orientation of the hominin remains illustrate a very low degree of dispersal of the bones, indicative of very little disruption between death and burial, due to an absence of damage by scavengers and possible natural mummification. The very few carnivore-damaged bones and relative abundance of complete and/or articulated specimens, the presence of antimeric sets of bones in the faunal assemblage, as well as the diversity of the faunal spectrum, and the significant percentage of animals with climbing proclivities (such as carnivores and hominins) indicate that the majority of the faunal material recovered was most likely accumulated via a natural death trap. Their bodies came to rest in a deep area of the cave system with restricted access to iii scavengers. Skeletons and bones accumulated in a talus cone below a vertical shaft. There, they decomposed, and became buried without major disruption by biotic or abiotic agents. A new forensic approach, referred to as palaeoforensic taphonomy, was followed in each step of the taphonomic analysis of the two hominins in order to reconstruct the processes of decay, disarticulation, burial and preservation. Results show that both individuals did probably not enter the cave system at the same time. They reached skeletonization and were slightly weathered before final burial, indicating several years of exposure before burial. Insects proved to be the primary modifiers of the hominin remains, pre- and post-depositional with hide beetles (Omorgus squalidus) providing the closest match for some of the fossil modifications observed. Based on the high number of articulated remains, the absence of preferential orientation for the elongated bones and of significant movement of the hominin remains inside the deposit, the debris flow hypothesis that was previously proposed as the principal agent to explain the burial of the hominins and other well-preserved animals is challenged. Evidence of natural mummification before burial for MH1 and MH2 suggests the possible preservation of soft tissue. The innovative 3D techniques applied in this research to conduct the spatial analysis of the fossils proved useful to address taphonomic questions, and will serve as a guide for future excavations of the Malapa in situ deposits, especially for locating the missing skeletal elements of MH1 and MH2.

Grupos de ratos Wistar e cães Beagle foram submetidos a dietas com dopagem de urânio, iniciando-se no desmame do animal e prolongando-se até sua maturidade. O conteúdo de urânio em ossos foi determinado por duas técnicas nucleares: nêutron-fissão e análise por ativação neutrônica, obtendo-se microdistribuição e conteúdos totais, respectivamente. O conteúdo total de U em ossos de ratos, em função da quantidade ingerida (medida em ppm de U na ração), exigiu um comportamento tendendo à saturação para doses de urânio na vizinhança de 20 ppm, sendo verificado também ser este o limiar toxicológico do U em ratos. Observou-se uma alteração do regime de saturação para outro, linear crescente, em dosagens superiores a 20 ppm. Esta ocorrência foi discutida em termos de uma provável falência renal de origem toxicológica. A microdistribuição de U em seções transversais do colo femoral de Beagles mostrou que, contrariamente ao que ocorre em situações de ingestão aguda e única, esse radionuclídeo distribui-se igualmente tanto no córtex quanto na medula óssea. Vários \"hot spots\" de U foram observados na região próxima ao endósteo. Foi desenvolvido um modelo biocinético para descrever a acumulação do U em função do tempo, e esse modelo foi validado vis-a-vis dados obtidos neste trabalho com ossos de Beagles. Com isso obteve-se, por extrapolação, que a saturação óssea de U ocorreria num período igual ou superior a 8 anos. Doses internas e microdoses foram acumuladas para a região da medula óssea, e as possíveis consequências radiobiológicas foram discutidas, tomando-se como exemplo ilustrativo a recente questão do urânio depletado disperso, via operações militares, nas regiões do Golfo Pérsico e Balcans. / Groups of Wistar rats and Beagle dogs were submitted to uranium doped diets, starting in the post-weaning period and extending till maturity. The uranium content in bones was determined by means of two techniques: neutron-fission and neutron activation analysis, to obtain microdistributions and total contents, respectively. The total content of U in bones of Wistar rats, as a function of the ingested amount (measured in terms of ppm of U in the food), showed a trend toward saturation for U dosages around 20 ppm, which also represents the toxicological threshold of U in Wistar rats, as verified in this work. Is was also observed, at dosages higher than 20 ppm, a change of the saturation regime into another linearly increasing. This fact was discussed in terms of a possible toxicologically originated renal failure. The U microdistribution in transverse sections of Beagle femoral shafts, showed that this radionuclide is equally distributed all along the cortex and marrow, which is at variance with experimental situations of single and acute dosages. Several U hot spots were observed at locations near to the endosteo. Is was developed a biokinetical model to describe accumulation as a function of time, and this model was validated by a comparison with data for Beagle bones obtained in this work. We came to the conclusion, by extrapolation of the model, that the U saturation in bone would take place after a period equal or higher to 8 years. Internal and microdoses imparted to the central bone marrow were calculated, and the possible radiobiological consequences were discussed, where the recent issue of depleted uranium dispersed in the environment, by means of military operations in the Gulf and Balkans regions, was used as a working example.

黃孕祺. / 論文(博士) -- 香港中文大學硏究院藝術部, 1995. / 參考文献 : 134-143. / Huang Yunqi. / 目錄 --- p.i-iii / 〈凡例〉 --- p.iv / Chapter 第一章 --- 書風的形式 --- p.1 -33 / Chapter 一、 --- 研究之目的 --- p.1 / Chapter 二、 --- 問題之關鍵 --- p.7 / Chapter 三、 --- 形式的特徵 --- p.13 / Chapter 四、 --- 術語的糸統 --- p.18 / Chapter 五、 --- 書風的詮釋 --- p.23 / Chapter 六、 --- 風格的分判 --- p.28 / Chapter 第二章 --- 書風的演變 --- p.34 -68 / Chapter 一、 --- 斷代的標準 --- p.34 / Chapter 二、 --- 世系與稱謂 --- p.39 / Chapter 三、 --- 母妣與名諡 --- p.49 / Chapter 四、 --- 貞人與稱謂 --- p.53 / Chapter 五、 --- 斷代新方案 --- p.58 / Chapter 六、 --- 風格和時代 --- p.63 / Chapter 第三章 --- 書風的意味 --- p.69 -108 / Chapter 一、 --- 意味之抉隱 --- p.69 / Chapter 二、 --- 取龜到藏龜 --- p.74 / Chapter 三、 --- 奉龜到徹龜 --- p.80 / Chapter 四、 --- 記事和記兆 --- p.86 / Chapter 五、 --- 卜辭的書契 --- p.93 / Chapter 六、 --- 殷契之成就 --- p.101 / 〈註釋〉 --- p.109 -131 / Chapter 第一章 --- 註 --- p.109 / Chapter 第二章 --- 註 --- p.115 / Chapter 第三章 --- 註 --- p.125 / 〈書刊簡稱表〉 --- p.132 -133 / 著錄 --- p.132 / 工具書 --- p.132 / 刊物 --- p.133 / 〈參考書目〉 --- p.134 -143 / 〈附表〉 --- p.144 -190 / 【表1.1】書風範型表 --- p.144 / 【表1.2】書風範型關係簡表 --- p.145 / 【表1.3】書風範型資料例 --- p.146 -149 / 【表2.1 .1】王世、稱謂、貞人關係表一： 王世、稱謂表 --- p.150 / 【表2.1.2】王世、稱謂、貞人關係表二： 貞人稱謂表 --- p.151 / 【表2.1.3a】】王世、稱謂、貞人關係表三： 貞人王世表（a) --- p.152 / 【表2.1.3b】】王世、稱謂、貞人關係表三： 貞人王世表（b) --- p.152 / 【表2 . 2】標準片表 --- p.153 -172 / 【表2.3】貞人同版表 --- p.173 -175 / 【表2.4a】 貞人繫聯表（I) --- p.176 -177 / 【表2.4b】 貞人繫聯表（II) --- p.178 / 【表2.5】「標準片」範型時期表 --- p.179 / 【表2.6】四期書風表 --- p.180 / 【表2.7】t期書風表 --- p.180 / 【表2.8】五期書風表 --- p.180 / 【表2.9】書風同異關係糸數簡表 --- p.181 / 【表2.10】書風同異關係系數詳表 --- p.182 -189 / 【表3.1】殷代龜卜程序表 --- p.190 / 〈附圖〉 --- p.1 -223 / 《合》 --- p.1 -202 / 《屯》 --- p.203 -217 / 《英》 --- p.218 -220 / 《東》 --- p.221 / 《懷》 --- p.222 -223

Bone makes up a framework that provides protection for internal body organs. The homeostasis of bone is maintained by a balanced process involving old bone degradation and new bone formation. However, this balance can be altered in pathophysiological conditions such as in postmenopausal osteoporosis and in patients with rheumatoid arthritis (RA). In recent years, new therapies have been developed to reduce bone resorption. However, there is disparity in patients’ response to these therapies. The reasons are unclear although age, gender, ethnic background and lifestyle have all been suggested to play a part. For patients with chronic inflammatory conditions, treatment was revolutionised by the discovery and application of biologic therapies that target pro-inflammatory proteins and/or pathways. However, whilst the anti-inflammatory effect of these biologic agents is well-established, their effect on bone loss is just emerging. In RA, it is not clear whether the beneficial anti-inflammatory effects of biologic anti-tumour necrosis factor alpha (TNFα) agents are accompanied by parallel improvements in bone erosion/density, whether there are differences between patient groups and what factors influence the response. In order to address these issues, a database on the factors that influence responsiveness of patients with osteoporosis to bisphosphonates, a treatment that suppresses bone resorption, was established. Based on the outcome of this study, the influence of the key factor(s) that affect bone response to treatment in combination with excess pro-inflammatory cytokine production on bone response in RA patients was determined. Significant improvement in bone mineral density (BMD) and plasma levels of bone biomarkers has been shown in this study with biologic anti-TNFα agents. The improvement in BMD was not always consistent with improvement the clinical response to treatment as assessed by changes in disease activity score 28(DAS28). The study also provides a mechanistic explanation for how blockade of TNFα in patients can reverse the balance of bone loss in patients with RA. Thus, the data show that treatment of patients with biologic anti-TNFα agents reduces the number of osteoclast precursors (OCs) in the blood.

Orientador: Luiz Antônio Salata / Banca: Osvaldo Magro Filho / Banca: Sérgio Luiz Scombatti Souza / Banca: Wilson Roberto Poi / Banca: Andreza Ribeiro Simioni / Resumo: A combinação de um fármaco fotossensível (FS) ativado por luz (vermelha, infravermelho ou ambas) forma uma das vertentes de aplicação da Terapia Fotodinâmica (TFD), que consiste na administração de um FS que posteriormente é ativado pela irradiação do LED ou Laser junto ao tecido, sendo que o FS ou a luz sozinhas, não apresentam citotoxicidade. O presente estudo teve por objetivos estabelecer o potencial regenerador do tecido ósseo para o reparo em calvária de coelho, utilizando três sistemas de liberação de drogas (DDS) de FS, estimulado pela combinação da fotobiomodulação de sistemas LED operando na faixa do visível e infravermelho. Foram utilizados 48 coelhos New Zealand White divididos em 3 grupos: Grupo LED 24/48 (dezoito coelhos) com aplicações de LED 24/48 horas após a cirurgia, Grupo LED 72/96 (dezoito coelhos) com aplicações de LED 72/96 horas após a cirurgia e Controle (doze coelhos) onde não houve aplicação de LED. Nos grupos experimentais foram realizadas 4 perfurações nas calvárias com preenchimento aleatoriamente de 1) Base em gel, 2) nanoemulsão carregada com FS, 3) lipossoma em gel com FS e 4) nanopartículas de albumina (BSA) carregada com FS. No grupo controle foram feitas duas perfurações, uma preenchida por osso autógeno e outra com coágulo. Dezesseis animais foram submetidos à eutanásia em cada tempo experimental: 5 dias, 10 dias e 20 dias. Lâminas histológicas foram feitas a partir dos defeitos e o osso neoformado foi mensurado. O uso de FS nos DDS não foi efetivo para abreviar o tempo de reparo ósseo em calvária de coelhos nos inervalos de tempo deste estudo / Abstract: The combination between photosensitizer substances with laser or LED (light emitting diode) form the photodynamic therapy (PDT) basis that consists of photosensitivity drug activated by low frequency light. This mechanism is used in soft tissue healing process to improve the oxygen tension leading to a fast revascularization. The objective of this study was to evaluate the effects of photosensitivity drugs activated through LED on bone healing process. Fourty eight New Zealand White rabbits were underwent to four bicortical calvaria defects made by 6.0 mm trephine drill. The defects were randomly filled up with (1) Gel, (2) Nanoemulsion + photosensitizer drug, (3) Liposome + photosensitizer drug, (4) NPS (nanostructure polymeric system) + photosensitizer drug. After 24/48 hours or 72/96 hours a LED were applied on all the rabbits. Sixteen animals were sacrificed, respectively, at 5, 10 and 20 days after surgery. Histological slides were prepared from each experimental site for histomorphometry and histological analysis. Bone graft was significant higher bone level in all experimental time points.. At 10 days liposome showed higher bone level than Gel (p=0,0161). However on 20 days, no difference was detected between the materials. The use of photosensitizer drugs activated by LED demonstrated do not achieve the stimulate bone formation on later time points on thsi presente study / Doutor

Osteoblasts are bone-forming cells and therefore they are responsible of the synthesis of type I collagen, the main component of bone matrix. However, there is an apparent disconnect between the regulation of osteoblast differentiation and bone formation since the synthesis of Type I collagen precedes the expression of Runx2, the earliest determinant of osteoblast differentiation. Recently, genetic experiments in the mouse have revealed the existence of an unexpected cross-regulation between bone and other organs. In particular this body of work has highlighted the importance of osteoblasts as endocrine cells to regulate whole-body glucose homeostasis by secretion of a hormone, osteocalcin. However, the fundamental question of why bone regulates glucose homeostasis remained to be answered. Therefore, in my thesis, considering that bone is a metabolically demanding organ that constantly renews itself, I hypothesized that characterizing the connection between the need of glucose as a main nutrient in osteoblasts and bone development will provide a key to deeper understanding of why bone regulates glucose homeostasis. My work shows here that glucose uptake through GLUT1 in osteoblasts is needed for osteoblast differentiation by suppressing the AMPK-dependent activation by phosphorylation at S148 of Smurf1 that targets Runx2 for degradation. I also uncovered the mechanism of action of Smurf1 in this setting. In a distinct but synergetic way, glucose uptake promotes bone formation by inhibiting a distinct function of AMPK. In turn, Runx2 favors Glut1 expression, and this feedforward regulation between Runx2 and Glut1 determines the onset of osteoblast differentiation during development and the extent of bone formation throughout life. Furthermore, I also identified that Smurf1 not only regulates osteoblast differentiation by targeting Runx2 for degradation but also contributes to whole-body glucose homeostasis by regulating the activation of osteocalcin by targeting the insulin receptor for degradation in vivo. These results identify Smurf1 as a determinant of osteoblast differentiation during development, of bone formation and glucose homeostasis post-natally. Most importantly, we show that these Smurf1 functions required AMPK-phosphorylation site S148 in vivo. Altogether, these results revealed the absolute necessity of glucose as a regulator of Runx2 accumulation during osteoblast differentiation and bone formation in vivo and highlight the fundamental importance of the intricate cross-talk between bone and whole-body glucose metabolism.

by Chong Wai Sing, Wilson. / Thesis submitted in: August 2002. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2003. / Includes bibliographical references (leaves 116-126). / Abstracts in English and Chinese. / ACKNOWLEDGEMENT --- p.i / ABBREVIATION --- p.ii / ABSTRACT (Chinese & English) --- p.iii / TABLE OF CONTENT --- p.vii / INDEX FOR FIGURES --- p.x / INDEX FOR TABLES --- p.xiii / Chapter 1. --- Introduction --- p.1 / Chapter 1.1 --- "Bone-tendon junction - types, structures and functions" --- p.2 / Chapter 1.1.1 --- Indirect insertion --- p.3 / Chapter 1.1.2 --- Direct insertion --- p.3 / Chapter 1.1.3 --- Functional adaptations of insertions --- p.4 / Chapter 1.2 --- Incidence and type of injuries near insertion site --- p.5 / Chapter 1.3 --- Treatment protocol for injuries near insertion site --- p.5 / Chapter 1.3.1 --- Non-operative versus operative approach --- p.5 / Chapter 1.3.2 --- Previous studies on validations of outcomes of difference repair methods --- p.6 / Chapter 1.4 --- Modes of healing underlying different repair approach --- p.7 / Chapter 1.4.1 --- Fracture healing --- p.7 / Chapter 1.4.2 --- Tendon healing --- p.8 / Chapter 1.4.3 --- Bone-tendon healing --- p.9 / Chapter 1.5 --- Objectives --- p.9 / Chapter 2. --- Materials and Methods --- p.12 / Chapter 2.1 --- Animal model --- p.13 / Chapter 2.2 --- Experimental design --- p.13 / Chapter 2.3 --- Surgery --- p.13 / Chapter 2.3.1 --- Bone-to-bone repair --- p.14 / Chapter 2.3.2 --- Bone-to-tendon repair --- p.14 / Chapter 2.3.3 --- Tendon-to-tendon repair --- p.15 / Chapter 2.4 --- Post-operative follow-up --- p.15 / Chapter 2.4.1 --- Radiographic examination --- p.15 / Chapter 2.4.2 --- Polychrome sequential labeling --- p.16 / Chapter 2.4.2.1 --- Reagents --- p.16 / Chapter 2.4.2.2 --- Route of administration --- p.16 / Chapter 2.5 --- Sampling --- p.17 / Chapter 2.6 --- Histology --- p.17 / Chapter 2.6.1 --- Decalcification --- p.17 / Chapter 2.6.1.1 --- Tissue decalcification --- p.17 / Chapter 2.6.1.2 --- Tissue processing --- p.17 / Chapter 2.6.1.3 --- Immunohistochemistry of collagen type II and III --- p.18 / Chapter 2.6.1.3.1 --- Reagents and solution preparation --- p.18 / Chapter 2.6.1.3.2 --- Experimental procedures --- p.20 / Chapter 2.6.2 --- Undecalcification --- p.22 / Chapter 2.6.2.1 --- Specimen preparations --- p.22 / Chapter 2.6.2.2 --- Toluidine blue staining --- p.22 / Chapter 2.7 --- Mechanical test --- p.23 / Chapter 2.7.1 --- Sample preparation --- p.23 / Chapter 2.7.2 --- Embedding procedures --- p.23 / Chapter 2.7.3 --- Measurement of cross-sectional area of healing interface --- p.23 / Chapter 2.7.3.1 --- CSA for BB --- p.23 / Chapter 2.7.3.2 --- CSA for BT and TT --- p.24 / Chapter 2.7.4 --- Tensile test --- p.24 / Chapter 2.7.4.1 --- Testing procedures --- p.24 / Chapter 2.7.4.2 --- Interpretation of testing results --- p.25 / Chapter 2.7.5 --- Statistical analysis --- p.26 / Chapter 3. --- Results --- p.42 / Chapter 3.1 --- Surgical outcome --- p.43 / Chapter 3.1.1 --- Radiographic examination --- p.43 / Chapter 3.1.1.1 --- Bone-to-bone healing --- p.43 / Chapter 3.1.1.2 --- Bone-to-tendon healing --- p.44 / Chapter 3.1.2 --- Fluorochrome injection --- p.44 / Chapter 3.2 --- Histology --- p.45 / Chapter 3.2.1 --- Bone-to-bone healing --- p.45 / Chapter 3.2.1.1 --- Gross anatomy --- p.45 / Chapter 3.2.1.2 --- Microscopic examination --- p.45 / Chapter 3.2.1.3 --- Polarised light microscopy --- p.46 / Chapter 3.2.1.4 --- Fluorochrome microscopy --- p.46 / Chapter 3.2.2 --- Bone-to-tendon healing --- p.47 / Chapter 3.2.2.1 --- Gross anatomy --- p.47 / Chapter 3.2.2.2 --- Microscopic examination --- p.47 / Chapter 3.2.2.3 --- Polarised light microscopy --- p.48 / Chapter 3.2.2.4 --- Fluorochrome microscopy --- p.49 / Chapter 3.2.3 --- Tendon-to-tendon healing --- p.49 / Chapter 3.2.3.1 --- Gross anatomy --- p.49 / Chapter 3.2.3.2 --- Microscopic examination --- p.49 / Chapter 3.2.3.3 --- Polarised light microscopy --- p.50 / Chapter 3.3 --- Mechanical testing --- p.50 / Chapter 3.3.1 --- Bone-to-bone healing --- p.50 / Chapter 3.3.1.1 --- Change of cross sectional area --- p.50 / Chapter 3.3.1.2 --- Load at failure --- p.50 / Chapter 3.3.1.3 --- Strength --- p.51 / Chapter 3.3.1.4 --- Energy --- p.51 / Chapter 3.3.2 --- Bone-to-tendon healing --- p.51 / Chapter 3.3.2.1 --- Change of cross sectional area --- p.51 / Chapter 3.3.2.2 --- Load at failure --- p.52 / Chapter 3.3.2.3 --- Strength --- p.52 / Chapter 3.3.2.4 --- Energy --- p.52 / Chapter 3.3.3 --- Tendon-to-tendon healing --- p.52 / Chapter 3.3.3.1 --- Change of cross sectional area --- p.53 / Chapter 3.3.3.2 --- Load at failure --- p.53 / Chapter 3.3.3.3 --- Strength --- p.53 / Chapter 3.3.3.4 --- Energy --- p.53 / Chapter 3.3.4 --- "Comparison of healing quality among BB, BT, and TT repair" --- p.54 / Chapter 3.3.4.1 --- Change of cross sectional area --- p.54 / Chapter 3.3.4.2 --- Load at failure --- p.54 / Chapter 3.3.4.3 --- Strength --- p.54 / Chapter 3.3.4.4 --- Failure mode --- p.55 / Chapter 4. --- Discussion --- p.102 / Chapter 4.1 --- Use of goat calcaneus-Achilles junction as a bone-tendon reseach model --- p.103 / Chapter 4.2 --- "Bone-to-bone, bone-to-tendon, and tendon-to-tendon fixation" --- p.104 / Chapter 4.3 --- Histological characterization of different healing tissues --- p.105 / Chapter 4.3.1 --- Bone-to-bone healing (Fracture healing) --- p.105 / Chapter 4.3.2 --- Bone-to-tendon healing --- p.106 / Chapter 4.3.3 --- Tendon-to-tendon healing --- p.106 / Chapter 4.3.4 --- Regeneration versus repair --- p.107 / Chapter 4.4 --- Spatial and temporal expression of different type of collagen in different form of healing --- p.108 / Chapter 4.5 --- Mechanical properties of healing interface under different form of fixation --- p.108 / Chapter 4.5.1 --- Failure mode --- p.110 / Chapter 4.6 --- Limitations --- p.111 / Chapter 4.6.1 --- Goat animal model --- p.111 / Chapter 4.6.2 --- Immunohistochemistry --- p.111 / Chapter 4.7 --- Future study --- p.112 / Chapter 5. --- Conclusion --- p.113 / Chapter 6. --- References --- p.116