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This project introduces a novel ultrasonic shearing-based fabrication method for synthesizing nanobubbles, which can then be utilized as a platform for any theranostic applications in clinical medicine, such as drug/gene delivery systems. Our standard in situ sonochemical synthesis of nanobubbles incorporates a perfluorocarbon gas core (300 μl) and an albumin outer shell, which are then incorporated into phosphate-buffered saline (4 ml) and later sonicated with a US probe. The initial optimization phase consisted of experimenting with various amounts of human serum albumin (HSA), which stabilizes the nanobubble gas core. Of the parameters (20 mg, 40 mg, and 80 mg HSA), 40 mg HSA significantly outperformed (pin vivo imaging nanobubbles in the liver. A continuation of this project will continue to optimize and expand on the theranostic applications of the US sheared nanobubbles in vivo and ex vivo in osteoporosis and the bone.

Keratins are fibrous structural proteins found in human hair that have been used to develop bioactive and biocompatible constructs for a wide variety of tissue engineering and healthcare applications. Their ubiquity, capacity for self-assembly, ease of use and versatility in blended materials, and ability to modulate cell behavior and promote tissue ingrowth have made keratins well-suited for the development of regenerative therapies. In particular, keratins have demonstrated bioactivity in both in-vivo and in-vitro studies, by altering immune and stem cell phenotype and function and promoting an anti-inflammatory/wound healing environment. This work seeks to build on previous research by investigating the ability of low and high molecular weight keratins to augment anti-inflammatory primary macrophage phenotypes and examining the influence of keratin biomaterials on cellular and inflammatory mechanisms in two models of injury and disease. Rodent models of blast induced neurotrauma (BINT) and severe osteoporosis were used to inform the development of 2D and 3D in-vitro models of macrophage/endothelial cell injury and osteogenic differentiation respectively. Keratin biomaterials exhibited some potential to alter macrophage and endothelial cell dynamics following blast, specifically by promoting anti-inflammatory (M2c-like) macrophage polarization and diminishing endothelial cell injury responses (i.e. endothelial glycocalyx shedding). A more clinically relevant model of osteoporosis found that stem cells harvested from older, osteoporotic animals demonstrated limited proliferative and bone differentiation potential compared to healthy cells. However, 3D constructs (especially keratin-based materials) were able to enhance calcification and osteogenic gene expression of diseased cells. These results highlight the complexity of macrophage phenotypic switching and cellular dynamics in these systems. However, keratin-based therapeutics may prove useful for facilitating tissue regeneration and limiting detrimental inflammatory and cellular responses in various models of injury and disease. / Ph. D. / Keratins are proteins found in human hair that have been used for a wide variety of healthcare applications. Their availability, ease of use as coatings, gels, and scaffolds, and their ability to alter cell function have made keratins well-suited for regenerative therapies. In particular, keratins have demonstrated the ability to alter immune and stem cell function by promoting a wound healing environment. This work seeks to investigate the ability of different keratins to enhance wound healing immune cell types and examine the influence of keratin materials on stem and blood vessel cell behavior in two models of injury and disease. Rodent models of blast-wave induced traumatic brain injury (concussion) and severe osteoporosis (bone brittleness) were used to develop cell culture models of immune cell and blood vessel cell injury as well as the conversion of stem cells to bone-building cells respectively. Keratin-based materials exhibited some potential to alter immune and blood vessel cell function following blast injury, specifically by promoting wound healing immune cell transformation and diminishing blood vessel cell injury responses. A more clinically relevant model of osteoporosis found that stem cells harvested from older animals had a more limited ability to divide and transform to bone cells compared to healthy cells. However, 3D gels (especially keratin-based materials)—unlike 2D coatings—were able to enhance calcium deposition and other bone markers in diseased cell cultures. These results highlight the complexity of cell responses in these systems. However, keratin-based therapeutics may prove useful for promoting tissue regeneration and limiting detrimental inflammatory and cellular responses in various models of injury and disease.

In recent years, space exploration has been driving studies that enable sustained human presence in space. In such studies, fluidics relating to biology have become important. Fluids in biological systems span from large-scale flows relevant to circulatory, digestion, and pulmonary systems, but also involve many micro-scale porous flows. Hence, space exploration is driving a novel need to characterize fluidics in microscales in microgravity conditions. In this work, we study the porous flow network within bones that stimulates cellular growth and has the potential to relate to osteoporosis (including driving osteoporosis in astronauts). To study this effect, computational fluid dynamics (CFD) simulations are performed on a microfluidic device with a hexagon structure and compared to experimental results in both normal gravity (1g) and microgravity (0g) via Blue Origin's New Shepard Vehicle (NS-23 attempt and NS-24 launch). CFD results have been created to predict the transport character of nutrients in the bones. These insights have the potential to lead to preventative measures for osteoporosis in astronauts.

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In cell culture, the cellular responses on Day 6 and Day 18, and matrix mineralization (Day 35) of human periosteal cells after stimulated by ESW, LIPUS and ESW+LIPUS treatments were studied. Our results showed that LIPUS only exerted transiently beneficial effects on Day 6, but no effect was observed on Day 18. In contrast, ESW inhibited the differentiation on Day 6, and then exerted a time-delayed stimulation effect on cellular response and matrix mineralization. Data of the ESW+LIPUS showed that it was mainly under ESW effects, but LIPUS might impact the beneficial effect of ESW on Day 18, leading to reduced ALP and matrix mineralization. The potentials of the osteocytes to function as mechanosensors and signal relay were also investigated with untreated periosteal cells that separately received conditioned medium from MLO-Y4 osteocyte-like cells, which received the ESW LIPUS and ESW+LIPUS treatments. The periosteal cells showed stimulated proliferation in the ESW+LIPUS and ESW groups, indicating that the stimulus of ESW was transferred in the conditioned medium. / In conclusion, although our in vivo and in vitro findings did not support our hypothesis of the beneficial effects of combined treatment, but ESW had been shown to improve BMD and bone microarchitecture in osteoporotic bone, by stimulation of osteogenic activities in osseous cells. ESW might potentially be developed as treatment for osteoporosis. Our study also indicated that stimulation of osteogenic activities may be the direct interaction of ESW on osteoblast/periosteal cells, or indirectly through biochemical signals relayed by the osteocytes which acted as mechanosensors. / Osteoporosis is a bone disorder with decreased bone mass and deteriorated microarchitecture, leading to increased fracture risk. By using non-invasive biophysical interventions that stimulate osteogenesis, i.e. extracorporeal shockwave (ESW) and low-intensity pulsed ultrasound (LIPUS), may reduce bone loss effectively. We hypothesized that the combined treatment of ESW and LIPUS might produce synergistic effects on osteoporotic bone. The aim of this study was to investigate the efficacy of using ESW treatment alone and combined treatment of ESW and LIPUS to increase bone mineral acquisition on intact osteoporotic bone in vivo, and to investigate their underlying mechanisms in vitro. / Ten osteoporotic goats were used and divided into ESW and ESW+LIPUS groups (n=5). The ESW group received shockwave at calcaneus, distal radius, and femoral condyle on the left limbs once per month. The ESW+LIPUS group also received ESW treatment monthly and LIPUS for 6 day/week. The opposite limbs served as contralateral control. After nine months, percentage BMD changes, mineral apposition rate, trabecular thickness in treatment sites were found higher than that of controls in both groups. Cumulatively increase of serum bone-specific alkaline phosphatase indicated that the improvements were due to the increased osteogenic activities in bone. Of all parameter, no significant difference was found between the ESW+LIPUS and ESW groups. / by Tam Kam Fai. / "August 2006." / Adviser: Kwok Sui Leung. / Source: Dissertation Abstracts International, Volume: 68-03, Section: B, page: 1550. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2006. / Includes bibliographical references (p. 156-184). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.

A pilot clinical trial was conducted after the in-vivo and in-vitro studies: Eight subjects fulfilled the inclusion criteria were recruited. However, the liver function tests of three subjects out of eight were found to be abnormal with elevated aspartate aminotransferase (AST) and alanine aminotransferase (ALT) level, which was not reported in previous toxicity test. The trial was suspended immediately and a follow-up test showed that the elevated AST and ALT level had reverted back to normal within one month after termination of OPR intake. Although we could not accomplish a RCT, the pilot study revealed potential hepatotoxicity of OPR on human beings and it would raise the safety awareness of investigators on the use of herbal remedies in future clinical studies. / After the in-vivo and in-vitro studies, a double-blinded, randomized, placebo-controlled clinical trial (RCT) was planned. Due to a lack of a Chinese version of instrument to measure osteoporosis-specific quality of life, an English version of the Osteoporosis-Targeted Quality of Life Questionnaire (OPTQoL) was translated into Chinese and linguistically validated according to the standard guideline. The newly formed Chinese OPTQoL can be used to assess the impact of new interventions on quality of life among Chinese osteoporosis patients. / Association of the incidence of postmenopausal osteoporosis and Kidney-Vacuity Syndromes in TCM was investigated with the aid of a Kidney-Vacuity Syndromes scoring questionnaire. In the study, postmenopausal women, who suffered from deficiency of kidney "qi" and kidney "essence", had a significantly higher incidence of osteoporosis. These findings strongly supported that replenishing kidney qi and kidney essence was a logical therapeutic principle in the formulation of OPR. / In conclusion, this study investigated the use of TCM on the treatment of postmenopausal osteoporosis in a systematic manner. It started from herbal formulation, basic science studies to clinical trial. It revealed beneficial effects of OPR on bones through in-vivo and in-vitro studies and demonstrated certain possible mechanism behind. On the other hand, the hepatotoxicity of OPR on human beings was also exposed and had not been reported in previous toxicity tests. The study provided valuable clinical data for other investigators on the potential hazards of herbal remedies although they had been validated as safe and effective in pre-clinical stage. / In search for safe, effective and low-priced medicine, the public have turned their attention to Traditional Chinese Medicine (TCM). Extensive experience has been accumulated in TCM regarding the diagnosis and treatment of osteoporosis, which often involves the prescription of kidney-tonifying herbs. Therefore, the aim of the study, firstly, was to explore the association of the incidence of postmenopausal osteoporosis and Kidney-Vacuity Syndromes in TCM, so as to formulate a rational kidney-tonifying herbal formula for osteoporosis research (OPR). Secondly, the effect of the formula was evaluated by in-vitro and in-vivo studies. Thirdly, the Osteoporosis-Targeted Quality of Life Questionnaire was linguistically validated from English to Chinese, which was expected to be one of the outcome measurement tools in future clinical trials. Lastly, a pilot clinical study was performed, which revealed some potential hazards of the formula on human beings which have not been shown in previous works. / Osteoporosis is a skeletal disorder which leads to an increased risk of bone fracture, disability or even death. It has become a major public health threat and the worldwide incidence of osteoporotic fracture is projected to increase two fold within the next 50 years. Postmenopausal women, being affected by a lack of estrogen, face a much higher risk of the disease. This study would therefore focus on type I osteoporosis (i.e. postmenopausal osteoporosis). Although current medications can slow down the bone deterioration process, their side effects and high cost had impaired patients' compliance with long term treatment. / The effect of OPR for the treatment of postmenopausal osteoporosis was then evaluated by in-vitro and in-vivo studies. In the in-vivo study, an osteoporosis model was established by performing ovariectomy on the four-week-old C57BL/6 mice. A high bone turnover rate was induced and OPR successfully slowed down the high turnover rate of bones by decreasing bone formation and resorption process without increasing the uterine linings. However, its beneficial effect on bones could not be detected on bone mineral density measurement. / The potential mechanism of action of OPR on bones was explored by in-vitro study. OPR was shown to induce cell proliferation and differentiation of osteoblast-like UMR 106 cells. Furthermore, the estrogenic activity of OPR was detected by MCF-7 cell line, which has been stably transfected with estrogen responsive elements (ERE). OPR was shown to possess an estrogenic activity in a dose dependent manner and was comparable to the positive control at a concentration of 200 and 1000 mug/ml. The induced estrogenic activity by OPR may be associated with the presence of phytoestrogen within the herbal formula. These findings suggested that the beneficial effect of OPR on bones might relate to its direct positive effect on osteoblast and its estrogenic-like activity. / Liong, Ching. / Adviser: Chun-tao Che. / Source: Dissertation Abstracts International, Volume: 73-03, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2009. / Includes bibliographical references (leaves ). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [201-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

吸煙是引起骨質疏鬆症的因素之一。臨床研究清楚表明吸煙者的骨密度降低，但其他干擾因素可能掩蓋了吸煙對骨頭的不良效果。使用動物模型用以研究吸煙和骨質疏鬆症之間是否有直接的因果關係與它潛在的機制是有必要的。為此，我們使用年輕和雌激素耗盡的小鼠作被動吸煙模型以及小鼠成骨細胞和破骨細胞株來作研究。 / 年輕的Balb/c小鼠暴露於2%或4% (v/v)的香煙煙霧中，代表中度和重度吸煙的人。骨代謝生物標誌物明顯增加，4%吸煙組在14週後股骨的微觀結構4%顯著下降，這相等於人類吸煙12年。此外，雌性Balb/c小鼠進行4%吸煙和/或卵巢切除術(OVX)。吸煙+OVX組增加血清中骨轉換指標水平。4%吸煙組的股骨生長板較薄。μ-CT數據進一步表明，相對骨體積(BV / TV)和結構模型指數(SMI)在吸煙組有顯著影響，而且在吸煙+ OVX組上有更大程度的影響。 / 在細胞研究中使用氯仿(CSE)和乙醇的香煙提取物(ESE)。CSE抑制小鼠細胞株RAW 264.7形成破骨細胞，並刺激小鼠成骨細胞株的分化和功能。這個與體內研究矛盾的結果暗示直接從煙霧中提取的化學成分並不是引起骨質疏鬆的元兇。影響骨代謝的很可能是其他從煙霧中生成的活性代謝物和一些吸煙引起的內源性激素物質。在吸煙引起的骨質流失中，這些代謝物或內源性物質可能是非常重要的。 / 有見及此，4%吸煙小鼠的血清用以研究其對成骨細胞和破骨細胞活動的影響。吸煙小鼠血清顯著降低在成骨細胞中鹼性磷酸酶(ALP)活性和鈣沉積，一些成骨細胞標記基因和蛋白表達均下降，而且 Wnt/β-catenin信號通路下調。此外，吸煙小鼠血清顯著增加形成破骨細胞的數量，組織蛋白酶K的基因和蛋白表達增加，在NF-κB和p-38 MAPK信號傳導途徑的信號分子表達增加。 / 總而言之，大量吸煙可能影響年輕小鼠和雌激素耗竭小鼠的骨代謝和微結構，通過類似的行動機制，人類也可能有同樣的骨疾病風險。這項研究揭示了吸煙導致的骨質疏鬆症在青少年和絶經後婦女的發病機制。這也給我們線索如何預防和治療與吸煙有關的骨骼疾病。這項研究還傳達了一個明確的信息：在年輕時應開始應控制吸煙。 / Cigarette smoking is one of the risk factors for osteoporosis. Clinical studies clearly showed that smokers have lower bone mineral density, but other confounding factors could mask the adverse actions of smoking on bones. Animal models are warranted to study the direct causal relationship between cigarette smoking and osteoporosis, and also the underlying mechanisms. In this regard, we used a mouse passive smoking model in both young and estrogen depleted mice, and the mouse osteoblast and osteoclast cell lines. / Young Balb/c mice were exposed to 2 or 4% (v/v) of cigarette smoke, similar to moderate or heavy smoking respectively in humans. Biomarkers for bone turnover were increased and bone microstructure of femur was significantly deteriorated after 4% smoking for 14 weeks which is similar to cigarette smoking for 12 years in humans. Furthermore, the effects of heavy smoking on ovariectomized mice were also investigated. Female Balb/c mice were subjected to 4% cigarette smoking and/or ovariectomy (OVX). Cigarette smoking together with OVX further increased the levels of bone turnover markers in serum. Femur growth plate was thinner in the 4% smoking group when compared to those in the SHAM- and OVX-operated groups. Micro-CT data further indicated that the relative bone volume (BV/TV) and structural model index (SMI) were significantly affected in the smoking groups, and to a greater extent in the 4% smoking + OVX group. / Chloroform (CSE) and ethanol smoke extracts (ESE) were used in cell studies. CSE suppressed the formation of osteoclasts, and stimulated the differentiation and function of mouse osteoblasts. These findings are contradictory to those found in in vivo study implying that chemical components directly extracted from cigarette smoke are not the culprits in causing bone disorder in animals. It is likely that other active metabolites from cigarette smoke and some endogenous hormonal substances released by cigarette smoking could affect bone metabolism. These active metabolites together with the endogenous bone hormones are perhaps crucial in smoking-induced bone loss in the body. / In view of this hypothesis, sera from 4% smoking mice were used to investigate their effects on osteoblast and osteoclast activities. It was found that the alkaline phosphatase (ALP) activity and calcium deposition in osteoblast were reduced significantly by the sera from smoking mice. Gene and protein expressions of some osteoblast markers were also decreased. The downregulation of Wnt/β-catenin signaling pathway was observed after the treatment with the serum obtained from the 4% smoking group. Moreover, the number of osteoclasts being formed was increased significantly by the smoking mouse serum. Cathepsin K gene and protein expressions were also induced. The increased expressions of the signaling molecules including NF-κB and p-38 MAPK were also observed. / In conclusion, heavy cigarette smoking could deteriorate bone metabolism and microstructures in young female and also estrogen depleted mice. The same kind of risk in bone disease may also apply to humans through similar mechanisms of action. This study sheds light in understanding the pathogenesis of smoking-induced bone disorders in teenagers and also postmenopausal women. It also gives us clues how to prevent and treat smoking related bone diseases. This study also conveys a clear message that cigarette smoking control should be started in young ages. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Chan, Lok Yi Ruby. / Thesis (Ph.D.) Chinese University of Hong Kong, 2014. / Includes bibliographical references (leaves 182-207). / Abstracts also in Chinese. / Chan, Lok Yi Ruby.

As the population ages, osteoporosis-related fractures represent a major and costly public health concern that is associated with increased morbidity and mortality in the United States, particularly in postmenopausal women [1]. A Surgeon General’s Reported has pointed out the importance of early diagnosis and appropriate treatment of bone diseases [2]. Treatment is typically indicated based on a bone mineral density (BMD) value of osteoporosis or a prior fragility fracture. Of note, many fragility fractures occur in postmenopausal women with non-osteoporotic BMD values. More significantly, a prior fragility fracture, particularly a prevalent vertebral fracture (VF), is a strong predictor for the elevated risk of subsequent fractures [3-7]. Hence, early identification of VFs is of great importance for initiating pharmacological therapy in women who may not otherwise be treated in order to prevent future fractures. VFs are often subclinical which require additional efforts to identify these fractures [8]. Lateral dual-energy X-ray absorptiometry (DXA) scanning of the entire spine for vertebral fracture assessment (VFA) has been proposed by the International Society for Clinical Densitometry (ISCD) as an alternative of x-ray for the diagnosis of VFs [9]. Also, the National Osteoporosis Foundation (NOF) has provided guidelines when VFA should be performed [10]. However, the effectiveness of VFA as a screening tool for the identification of prevalent VFs is unclear and the cost-effectiveness of VFA is unknown, both limiting the implementation of VFA into routine care. Therefore, I conducted a systematic review and meta-analysis, the results of which have shown that the weighted pooled prevalence of VFA-detected VFs in asymptomatic women was 28%. Given that VFA is effective, I further evaluated the cost-effectiveness of VFA as a screening tool to reduce future osteoporotic fracture risk in U.S. postmenopausal women. The reference-case analysis has shown that VFA has the greatest cost-saving when the screening is initiated at age 65 years and with follow-up screening every 5 years. These findings support the NOF guidelines for the diagnostic use of VFA. There are some women with increased risk for secondary osteoporosis who may not be eligible for BMD or VFA screening due to their younger age, for example, women with human immunodeficiency virus (HIV) infection. Therefore, an accurate fracture risk assessment tool is an important component in the management of bone health in HIV-infected women. The interests of validating the predictive accuracy of FRAX® (a widely accepted fracture risk prediction tool in general population [11]) arose from the reported poor performance of FRAX in older HIV-infected men [12]. I validated FRAX performance in HIV-infected women using the Women’s Interagency HIV study (WIHS), suggesting that FRAX also underestimated fracture risk in HIV-infected women, but improved with the addition of DXA parameters. The results of the above studies demonstrate the potential role of VFA in reducing future fracture risk in women with prevalent VFs and the cost-effectiveness of incorporating VFA into routine screening for osteoporosis in postmenopausal women. Data were also provided for improving the fracture prediction in people with secondary osteoporosis using HIV infection as a model. These data may inform clinicians, policy makers and insurers on the benefit of including disease specific risk factors for fracture prediction and VF identification tools in the fight to prevent osteoporosis related fractures.

by Martin Li. / Year shown on spine: 1997. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1996. / Includes bibliographical references (leaves 150-157). / DECLARATION --- p.II / ABSTRACT --- p.III / ACKNOWLEDGEMENTS --- p.VII / CONTENTS --- p.VIII / LIST OF ABBREVIATIONS --- p.XIV / LIST OF TABLES --- p.XVI / LIST OF CHART --- p.XXIII / LIST OF FIGURES --- p.XXIV / Chapter CHAPTER 1 --- OBSTRUCTIVE AIRWAY DISEASE: PUBLIC HEALTH AND CLINICAL ASPECTS --- p.1 / Chapter 1.1. --- Background --- p.1 / Chapter 1.2. --- Magnitude of the problem --- p.2 / Chapter 1.2.1. --- Asthma --- p.2 / Chapter 1.2.2. --- Chronic obstructive pulmonary disease --- p.3 / Chapter 1.2.3. --- Prevalence of osteoporosis in Hong Kong --- p.4 / Chapter 1.2.4. --- History of asthma care --- p.5 / Chapter 1.2.5. --- Treatment of OAD --- p.5 / Chapter 1.3. --- Side effects of Glucocorticoid in OAD patients --- p.6 / Chapter 1.4. --- Side effccts of inhaled corticosteroids in OAD patients --- p.7 / Chapter 1.5. --- Trend of asthma therapy in Hong Kong --- p.8 / Chapter CHAPTER 2: --- OSTEOPOROSIS: PUBLIC HEALTH AND CLINICAL ASPECTS --- p.11 / Chapter 2.1. --- Bone Biology --- p.11 / Chapter 2.2. --- Skeletal Organisation --- p.11 / Chapter 2.3. --- Bone remodelling --- p.12 / Chapter 2.4. --- Effect of corticosteroids on bone remodelling --- p.13 / Chapter 2.5. --- Corticosteroids induccs osteoporosis --- p.13 / Chapter 2.6. --- Factors affecting BMD --- p.14 / Chapter 2.6.1. --- Peak bone mass --- p.14 / Chapter 2.6.2. --- Ethnic factors --- p.14 / Chapter 2.6.3. --- Aging --- p.15 / Chapter 2.6.4. --- Calcium intake --- p.15 / Chapter 2.6.5. --- Oestrogen --- p.16 / Chapter 2.6.6. --- Alcohol consumption --- p.17 / Chapter 2.6.7. --- Cigarette smoking --- p.17 / Chapter 2.7. --- Physical activity and BMD --- p.17 / Chapter 2.8. --- Body composition in Chinese subjects --- p.18 / Chapter CHAPTER 3 --- "PHASE I: BODY COMPOSITION AND BONE MINERAL DENSITY IN OBSTRUCTIVE AIRWAY DISEASE PATIENT AND NORMAL CONTROL SUBJECTS: OBJECTIVES, SUBJECTS AND METHODS" --- p.20 / Chapter 3.1. --- Objectives --- p.20 / Chapter 3.2. --- Subjects and methods --- p.21 / Chapter 3.2.1 --- OAD patients --- p.21 / Chapter 3.2.1.1 --- Disease definition and selection criteria --- p.21 / Chapter 3.2.1.2. --- Normal Control subjects --- p.21 / Chapter 3.3. --- Power of estimation --- p.22 / Chapter 3.4. --- Survey methods --- p.22 / Chapter 3.5. --- Questionnaire --- p.23 / Chapter 3.6. --- Body composition and bone mineral density measurement --- p.23 / Chapter 3.6.1. --- Body composition analysis --- p.24 / Chapter 3.6.2. --- Lumbar spine and proximal hip bone mineral density analysis --- p.24 / Chapter 3.6.3. --- Routine quality control of measurements --- p.24 / Chapter 3.6.4. --- Precision on patient repositioning --- p.25 / Chapter 3.7. --- Statistical methods --- p.25 / Chapter 3.8. --- Bone mineral density of normal control subjects --- p.25 / Chapter CHAPTER 4 --- PHASE II: FLUORIDE IN THE TREATMENT OF OSTEOPOROSIS --- p.27 / Chapter 4.1. --- Introduction --- p.27 / Chapter 4.2. --- Mechanisms of action --- p.28 / Chapter 4.2.1. --- Antiresorptive effect of fluoride --- p.28 / Chapter 4.2.2. --- Force-oriented osteogenic effect of fluoride --- p.28 / Chapter 4.2.3. --- Biochemical osteogenic effect --- p.29 / Chapter 4.3. --- Effect of fluoride salts on BMD: results of clinical trials --- p.29 / Chapter 4.4. --- Effcct of fluoride on bone histomorphology --- p.30 / Chapter 4.5. --- Compliance with sodium fluoride therapy --- p.31 / Chapter 4.6. --- Contradiction of fluoride treatment --- p.31 / Chapter 4.7. --- Sodium monofluorophosphate preparation --- p.32 / Chapter CHAPTER 5 --- PHASE II: THE EFFECTS OF FLUORIDE ON BONE MINERAL DENSITY OF OAD PATIENTS ON STEROID TREATMENT --- p.37 / Chapter 5.1. --- Objectives --- p.37 / Chapter 5.2. --- Subjects and methods --- p.37 / Chapter 5.2.1. --- Power of the study --- p.37 / Chapter 5.2.2. --- Subjects --- p.37 / Chapter 5.2.3. --- Method of randomisation --- p.38 / Chapter 5.2.4. --- Treatment modalities --- p.39 / Chapter 5.2.4.1. --- Treatment group --- p.39 / Chapter 5.2.4.2. --- Control group --- p.39 / Chapter 5.2.5. --- Bone mineral density measurements --- p.39 / Chapter 5.2.6. --- Routine quality control of measurement and precision on patient repositioning --- p.40 / Chapter 5.2.7. --- Methods of monitoring drug compliance --- p.40 / Chapter 5.2.8 --- Statistical methods --- p.40 / Chapter CHAPTER 6 --- RESULTS FOR PHASE I --- p.42 / Chapter 6.1. --- Statistical power of this phase of the study --- p.42 / Chapter 6.2. --- Clinical features of OAD subjects on inhaled steroid --- p.42 / Chapter 6.3. --- Anthropometric measurements and bone mineral density --- p.45 / Chapter 6.4. --- Analysis of covariance for BMDs differences --- p.48 / Chapter 6.5. --- Multiple regression --- p.50 / Chapter 6.6 --- Correlation --- p.51 / Chapter CHAPTER 7 --- RESULTS FOR PHASE II: FLUORIDE AND CALCIUM TRIAL --- p.81 / Chapter 7.1. --- Factors affects the power of studies --- p.81 / Chapter 7.2. --- Clinical findings --- p.82 / Chapter 7.3. --- Body measurements and bone mineral densitometry --- p.85 / Chapter CHAPTER 8: --- DISCUSSION FOR PHASE I --- p.117 / Chapter CHAPTER 9: --- DISCUSSION FOR PHASE II: TRIDIN AND CALCIUM TRIAL --- p.124 / APPENDIX 1: QUESTIONNAIRE FOR OAD BONE MINERAL DENSITY STUDY --- p.132 / APPENDIX 2: BONE SCANS FROM HOLOGIC QDR2000 --- p.137 / APPENDIX 3. TABLES AND REFERENCE CURVES FOR NORMAL HONG KONG CHINESE FEMALE OR MALE BMD --- p.142 / REFERENCE --- p.150