Bone fracture, particularly that occurring in osteoporotic conditions, has become a major health issue. Fracture healing is a well-orchestrated regenerative process, the enhancement of which has been one of the major goals in fracture management. Low-magnitude high-frequency vibration (LMHFV) is osteogenic for intact bone and beneficial for limb blood circulation, which implies a potential of enhancement for fracture healing. Three parts of the experiments were conducted in this study to test the hypothesis that LMHFV would accelerate fracture healing by promoting chondrogenesis, endochondral ossification, and remodeling in both normal and osteoporotic bones. / Part I study. Three-month-old female SD rats underwent closed femoral fracture and were randomized into either vibration group (VG-I, 35Hz, 0.3g, 20min/day, 5days/week) or sham-treated control group (CG-I). Femora were harvested at 1, 2 and 4 weeks for micro-CT analysis, histomorphometry, and mechanical testing. Part II study. Osteoporotic model was established in nine-month-old SD rats after three months of inducement following ovariectomy. Similar grouping (VG-II and CG-II) and treatment regimes were performed after fracture, with the femora harvested at 2, 4 and 8 weeks for assessments like those in the Part I study. Part III study. After fracture, 3-month-old female SD rats were grouped (VG-III and CG-III) and treated as in the Part I study. At 1, 2 and 4 weeks, femora were collected for gene quantification (Col-1, Col-2, BMP-2, VEGF, and TGF-beta1) using real-time PCR. Type I and II collagens were located immunochemically in histological sections. / Results of the Part I and II studies demonstrated that LMHFV promoted callus formation (together with chondrogenesis), mineralization (endochondral ossification), and remodeling, which led to faster healing and better mechanical outcomes in both normal and osteoporotic fractures. In molecular level, the effect of LMHFV was reflected by the stimulation of chondrogenesis and osteogenesis related matrix collagen formation and growth factor expression. The molecular data echo Part I and II findings well. This study proved that LMHFV accelerated fracture healing by promoting chondrogenesis, endochondral ossification, and remodeling in both normal and osteoporotic bones, and indicated great potential of its future clinical application on fracture healing. / Shi, Hongfei. / Adviser: Kwok-Sui Leung. / Source: Dissertation Abstracts International, Volume: 70-06, Section: B, page: 3422. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2008. / Includes bibliographical references (leaves 180-201). / 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.

Chow, Dick Ho Kiu. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (leaves 93-103). / Abstracts in English and Chinese. / Abstract --- p.ii / Publications --- p.vii / Acknowledgement --- p.viii / Table of Contents --- p.x / List of Figures --- p.xiv / List of Tables --- p.xv / List of Abbreviations --- p.xvii / Chapter 1 --- Introduction --- p.1 / Chapter 1.1 --- Bone and its Cellular Components --- p.1 / Chapter 1.1.1 --- Cellular Components of Bone --- p.1 / Chapter 1.1.2 --- Macroscopic Structure --- p.4 / Chapter 1.1.3 --- Microscopic Structure --- p.4 / Chapter 1.2 --- Fracture Healing --- p.5 / Chapter 1.2.1 --- Inflammation --- p.6 / Chapter 1.2.2 --- Soft Callus Formation --- p.6 / Chapter 1.2.3 --- Hard Callus Formation --- p.7 / Chapter 1.2.4 --- Bone Remodeling --- p.7 / Chapter 1.3 --- Low Magnitude High Frequency Vibration (LMHFV) Stimulation --- p.7 / Chapter 1.3.1 --- Mechanical Stimulation --- p.10 / Chapter 1.3.2 --- Effect of LMHFV on Bone --- p.12 / Chapter 1.4 --- Osteoporosis and Osteoporotic Fractures --- p.16 / Chapter 1.4.1 --- Epidemiology of Osteoporotic Fracture --- p.17 / Chapter 1.4.2 --- Pathophysiology --- p.17 / Chapter 1.4.3 --- Osteoporotic Fracture Healing --- p.20 / Chapter 1.5 --- Bisphosphonate --- p.23 / Chapter 1.5.1 --- Background --- p.23 / Chapter 1.5.2 --- Mechanism of Action --- p.24 / Chapter 1.5.3 --- U sage of Bisphosphonate --- p.25 / Chapter 1.5.4 --- Bisphosphonate Effects on Fracture Healing --- p.27 / Chapter 1.6 --- Hypothesis --- p.27 / Chapter 1.7 --- Study Plan --- p.28 / Chapter 1.7.1 --- Objectives --- p.28 / Chapter 2 --- Method --- p.29 / Chapter 2.1 --- Ovariectomized Rat Femoral Fracture Model --- p.29 / Chapter 2.1.1 --- Ovariectomized Rat Model. --- p.29 / Chapter 2.1.2 --- Closed Femoral Fracture --- p.31 / Chapter 2.2 --- Study Design --- p.32 / Chapter 2.3 --- LMHFV Treatment Protocol --- p.32 / Chapter 2.4 --- Bisphosphonate Treatment Protocol --- p.35 / Chapter 2.4.1 --- Pharmacological Parameters --- p.35 / Chapter 2.4.2 --- Ibandronate Injection Solution Preparation --- p.37 / Chapter 2.4.3 --- Injection --- p.37 / Chapter 2.5 --- Fluorochrome Labeling --- p.38 / Chapter 2.5.1 --- Fluorochrome Preparation --- p.38 / Chapter 2.5.2 --- Injection --- p.38 / Chapter 2.6 --- Assessments --- p.39 / Chapter 2.6.1 --- Radiographic Analysis --- p.39 / Chapter 2.6.2 --- uCT Analysis --- p.40 / Chapter 2.6.3 --- Undecalcified Histology --- p.43 / Chapter 2.6.4 --- ELISA Analysis on Bone Markers --- p.47 / Chapter 2.7 --- Statistical Analysis --- p.50 / Chapter 3 --- Results --- p.51 / Chapter 3.1 --- Radiographic Analysis --- p.52 / Chapter 3.1.1 --- Callus Bridging Rate --- p.52 / Chapter 3.1.2 --- Callus Width and Area --- p.52 / Chapter 3.2 --- uCT Analysis --- p.55 / Chapter 3.3 --- Histomorphometric Analysis --- p.61 / Chapter 3.3.1 --- Bone Mineralization Rate --- p.61 / Chapter 3.4 --- Bone Markers Analysis --- p.64 / Chapter 3.4.1 --- Osteocalcin --- p.64 / Chapter 3.4.2 --- TRAP5b --- p.64 / Chapter 3.4.3 --- Summary --- p.67 / Chapter 4 --- Discussion --- p.69 / Chapter 4.1 --- LMHFV Enhanced Bone Remodeling --- p.69 / Chapter 4.1.1 --- LMHFV Reversed Bis Inhibition on Bone Remodeling --- p.70 / Chapter 4.1.2 --- LMHFV Effect on Osteoclastic Resorption During Bone Re-modeling --- p.71 / Chapter 4.2 --- Enhanced Fracture Healing by LMHFV --- p.72 / Chapter 4.2.1 --- Acceleration of Fracture Healing by LMHFV --- p.72 / Chapter 4.2.2 --- LMHFV Inhibits Osteoclast Activity in the Early Phase of Healing --- p.73 / Chapter 4.2.3 --- LMHFV Stimulates Osteoblast Activity in the Early Phase of Healing --- p.74 / Chapter 4.3 --- Bis Delays Fracture Healing --- p.75 / Chapter 4.4 --- Experimental Design --- p.78 / Chapter 4.4.1 --- Inhibition Study --- p.78 / Chapter 4.4.2 --- Bisphosphonate Injection Protocol --- p.79 / Chapter 4.4.3 --- Individual Analysis of Bone Formation and Resorption . --- p.81 / Chapter 4.5 --- Clinical Implications --- p.84 / Chapter 4.5.1 --- LMHFV Enhanced Remodeling --- p.84 / Chapter 4.5.2 --- Bisphosphonate Delayed Remodeling --- p.85 / Chapter 4.6 --- Limitations --- p.85 / Chapter 4.6.1 --- Measurement of Bone Resorption --- p.85 / Chapter 4.6.2 --- Osteoporotic Fracture Model --- p.86 / Chapter 4.6.3 --- Inhibition of Bone Remodeling --- p.87 / Chapter 4.7 --- Future Studies --- p.88 / Chapter 4.7.1 --- LMHFV Effect on Osteoclast in vitro --- p.88 / Chapter 4.7.2 --- Biomechanics of Fracture Callus --- p.89 / Chapter 4.7.3 --- LMHFV Effect on Leptin- Adrenergic Pathway --- p.89 / Chapter 5 --- Conclusion --- p.91 / Bibliography --- p.93

Chung, Shu Lu. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2008. / Includes bibliographical references (leaves 109-118). / Abstracts in English and Chinese. / Abstract --- p.i-iv / 中文摘要 --- p.v-vii / Publications --- p.viii / Acknowledgements --- p.ix / List of Abbreviations --- p.x-xi / Index for Figures --- p.xii-xiv / Index for Tables --- p.xv / Table of Contents --- p.xvi-xix / Chapter Session 1: --- Introduction --- p.1 / Chapter 1.1 --- Biology of fracture healing process --- p.2 / Chapter 1.1.1 --- Stage of inflammation --- p.2-3 / Chapter 1.1.2 --- Stage of soft callus formation --- p.3-4 / Chapter 1.1.3 --- Stage of hard callus formation --- p.4-5 / Chapter 1.1.4 --- Stage of bone remodeling --- p.5 / Chapter 1.2 --- Conventional treatments and its limitations --- p.5-6 / Chapter 1.3 --- Biological treatments in accelerating fracture healing process --- p.6-7 / Chapter 1.4 --- Biophysical treatments in accelerating fracture healing process --- p.7-8 / Chapter 1.4.1 --- Electromagnetic fields --- p.8-9 / Chapter 1.4.2 --- Shockwave --- p.9 / Chapter 1.4.3 --- Low intensity pulsed ultrasound --- p.9-11 / Chapter 1.5 --- Properties of ultrasound --- p.11 / Chapter 1.5.1 --- Ultrasound signals --- p.11-12 / Chapter 1.5.2 --- Attenuation of ultrasound --- p.12-14 / Chapter 1.5.3 --- Modes of ultrasound wave propagation --- p.14-15 / Chapter 1.5.4 --- Reflection and critical angle --- p.15-18 / Chapter 1.6 --- Insights from previous studies --- p.18-19 / Chapter 1.7 --- Hypothesis --- p.19 / Chapter 1.8 --- Study plan --- p.20 / Chapter 1.9 --- Objectives --- p.20 / Chapter Session 2: --- Materials and Methodology --- p.25 / Chapter 2.1 --- Materials --- p.26 / Chapter 2.2. --- Closed femoral fracture rat model --- p.26 / Chapter 2.2.1 --- Operation procedures --- p.26-27 / Chapter 2.3 --- Groupings --- p.27 / Chapter 2.4 --- Low Iintensity Pulsed Ultrasound treatment --- p.28 / Chapter 2.4.1 --- Incident angles determination --- p.28 / Chapter 2.4.2 --- LIPUS devices --- p.29 / Chapter 2.4.2 --- Set up of standardized platform --- p.29-30 / Chapter 2.4.4 --- Treatment procedure --- p.30 / Chapter 2.5 --- Radiographic analysis --- p.31 / Chapter 2.6 --- Micro-Computed Tomography --- p.32 / Chapter 2.6.1 --- Micro-Computed Tomography scanning --- p.32 / Chapter 2.6.2 --- Micro-Computed Tomography analysis --- p.32-33 / Chapter 2.7 --- Histology --- p.34 / Chapter 2.7.1 --- Sample preparation --- p.34 / Chapter 2.7.2 --- Histomorphometrical analysis --- p.34-35 / Chapter 2.8 --- Mechanical Testing --- p.35 / Chapter 2.9 --- Statistical analysis --- p.35 / Chapter Session 3: --- Results --- p.48 / Chapter 3.1 --- Radiographic analysis --- p.49 / Chapter 3.1.1 --- Qualitative analysis - Callus bridging rate --- p.49 / Chapter 3.1.2 --- Quantitative analysis - Callus area and callus width --- p.49-50 / Chapter 3.2 --- Micro-computed tomography analysis --- p.50 / Chapter 3.2.1 --- Qualitative analysis - 3D reconstructed images --- p.50-51 / Chapter 3.2.2 --- Quantitative analysis - Bone volume of callus --- p.51 / Chapter 3.2.3 --- Quantitative analysis - Bone mineral density and bone mineral content --- p.51-52 / Chapter 3.3 --- Biomechanical test --- p.52-53 / Chapter 3.4 --- Histomorphological analysis --- p.53 / Chapter 3.4.1 --- Qualitative analysis --- p.53 / Chapter 3.4.2 --- Quantitative analysis --- p.53-54 / Chapter Session 4: --- Discussion --- p.85-87 / Chapter 4.1 --- Enhancement effects of LIPUS at different incident angles --- p.88 / Chapter 4.1.1 --- LIPUS transmitted at 350 accelerated the fracture healing process --- p.88 / Chapter 4.1.1.1 --- Callus bridging and callus mineralization --- p.88-89 / Chapter 4.1.1.2 --- Dose dependent effects of LIPUS -Maximization of ultrasound energy --- p.89-90 / Chapter 4.1.2 --- LIPUS transmitted at 35° enhanced the restoration of mechanical properties in fracture healing process --- p.90 / Chapter 4.1.2.1 --- Biomechanical properties --- p.90-91 / Chapter 4.1.2.2 --- Bone mineral density and bone mineral content --- p.91-92 / Chapter 4.1.2.3 --- Highly mineralized callus area and volume --- p.92-93 / Chapter 4.2 --- 35° may be the critical angle for further enhancing fracture healing --- p.93 / Chapter 4.2.1 --- LIPUS transmitted at 35° may be the first critical angle in this study --- p.93-95 / Chapter 4.2.2 --- Effects of different incident angles --- p.95-96 / Chapter 4.3 --- Mechanism of LIPUS at different incident angles on fracture healing process --- p.96 / Chapter 4.3.1 --- Endochondral ossification --- p.96-99 / Chapter 4.4 --- Advantages in using LIPUS transmitted at critical angle --- p.99 / Chapter 4.5 --- Limitations of the study --- p.100 / Chapter 4.5.1 --- Animal model --- p.100 / Chapter 4.5.2 --- Treatment sites of LIPUS transmitted at different incident angles --- p.100 / Chapter 4.5.3 --- Types of fracture --- p.101 / Chapter Session 5: --- Conclusions --- p.102-104 / Chapter Session 6: --- Future Studies --- p.105 / Chapter 6.1 --- Protocol and regime of LIPUS transmitted at different angles --- p.106 / Chapter 6.2 --- Periosteum-stripped fracture model --- p.106-107 / Chapter 6.3 --- Molecular mechanism of LIPUS transmitted at different incident angles --- p.107-108 / Bibliography --- p.109-118 / Appendix I --- p.119

Leung Ping-chung. / Thesis (D.Sc.)--Chinese University of Hong Kong, 1994. / Includes bibliographical references.

The loss of regenerative capacity of bone, from fetal to adult to aged animals, has been attributed not only to a decline in the function of cells involved in bone formation but also to alterations in the bone microenvironment that occur through development and aging, including extracellular matrix (ECM) composition and growth/trophic factor content. In the development of novel treatments for bone repair, one potential therapeutic goal is the restoration of a more regenerative microenvironment, as found during embryonic development. One approach to creating such a microenvironment is through the use of stem cells. In addition to serving as a differentiated cell source, pluripotent stem cells, such as embryonic stem cells (ESCs), may possess the unique potential to modulate tissue environments via local production of ECM and growth factors. ESC-produced factors may be harnessed and delivered to promote functional tissue regeneration. Such an approach to generate a naturally derived, acelluar therapy has been employed successfully to deliver osteoinductive factors found within adult bone, in the form of demineralized bone matrix (DBM), but the development of treatments derived instead from developing, more regenerative tissues or cells remains attractive. Furthermore, the derivation of regenerative materials from an ESC source also presents the added benefit of eliminating donor to donor variability of adult, cadaveric tissue derived materials, such as DBM. Thus, the objective of this project was to examine the osteoinductive potential harbored within the embryonic microenvironment, in vitro and in vivo. The osteogenic differentiation of mouse ESCs as embryoid bodies (EBs) was evaluated in response to phosphate treatment, in vitro, including osteoinductive growth factor production. The osteoinductivity of EB-derived material (EBM) was then compared to that of adult tissue-derived DBM, in vivo. Phosphate treatment enhanced osteogenic differentiation of EBs. EBM derived from phosphate treated EBs retained bioactive, osteoinductive factors and induced new bone formation, demonstrating that the microenvironment within osteogenic EBs can be harnessed in an acellular material to yield in vivo osteoinductivity. This work not only provides new insights into the dynamic microenvironments of differentiating stem cells but also establishes an approach for the development of an ESC-derived, tissue specific therapy.

Aim. The overall aims of this study were to develop a tailor-made educational intervention and to examine its effectiveness on short- and longer-term outcomes among Chinese patients with traumatic limb fractures who had undergone surgery. / Background. Fracture limb and undergoing surgery is the common problem after injury. It is the most common source of pain and anxiety and research continues to demonstrate a high prevalence of unrelieved pain in injured patients who have undergone surgery. Patient's belief in pain is the major barrier in pain management. Strategies directed to have appropriate educational interventions are urgently needed to improve patient outcomes for those suffering acute pain after surgery for traumatic limb fracture. / Conclusion. The C-BEI was effective in terms of reducing the pain barrier, providing post-operative pain relief, reducing anxiety, and improving sleep satisfaction in patients with fractured limbs during their first week of hospitalization after surgery. This study has generated evidence supporting the use of a C-BEI in acute pain management. / Method. The study was conducted in the orthopaedic wards of two regional hospitals in Hong Kong and comprised two phases. In phase one, qualitative interviews were conducted with twenty-six Chinese patients who had traumatic limb fractures and were undergoing surgery regarding their experiences of and beliefs about pain management. Ten orthopaedic nurses were also interviewed about their perceived pain management practices and the barriers that prevented better pain control among patients. The findings from these qualitative interviews were used to develop a cognitive behavioural approach educational intervention (C-BEI). C-BEI was used to enhance knowledge of pain, modify their beliefs about pain management and promote positive coping thoughts and behaviour. The C-BEI consisted of two sessions. The first was a 30-minute session comprised a combination of patient education and breathing relaxation exercise and conducted at T0 (1 day before surgery). A 30-minute reinforcement session was conducted at day 7 after surgery (T3). / Results. A total of 125 participants completed the study, with 62 in the experimental group and 63 in the control group. The participants were homogenous in terms of demographic data (P > 0.05) and baseline clinical characteristics (p > 0.05). The short-term outcomes (from T0 to T3) for the participants in the experimental group were a statistically significant with lower pain barrier (p = .003), lower level of pain (p = .003), lower level of anxiety (p < .001), and better sleep satisfaction (p = .001) than the control group. The experimental group had a significantly higher frequency of analgesic use at T2 (p < .001) and better self-efficacy in pain management at T3 (p = .011) than the control group. There were no statistically significant differences in the total length of stay in hospital, although the mean length of stay was shorter in the experimental group than in the control group (8.1 day VS 10.1 days). For longer-term effects, the C-BEI was effective at the post-operative stage in anxiety reduction ( p = .002) and sleep satisfaction improvement (p = .002). There were no statistically significant differences for the VAS pain level, GSE scores, physical health summary component (PCS) and mental health summary component (MCS) of the SF36 between two groups over three months, although the experimental group had better scores in the mental health dimension. Findings of the process evaluation showed that most participants perceived the C-BEI as effective in enhancing their knowledge on pain management and the use of analgesics, and helping them to cope with pain, the could sleep better and regain self-control. / The main study was conducted in phase II which consisted of outcomes and process evaluation. A quasi-experimental design of two groups' pre-test and post-test between subjects was employed for the outcomes evaluation. All participants in the experimental group received the C-BEI and usual care, whereas those in the control group received usual care only. The short-term outcomes were treated as primary outcomes and evaluated in terms of the participants' pain barrier score, pain level (Visual Analogue Pain Scale: VAS, anxiety level (State-Trait Anxiety Inventory:STAI), sleep satisfaction, self-efficacy in pain management (General Self Efficacy Scale: GSE), and frequency of analgesic use. All of which were measured at T0, T1 (day 2), T2 (day 4), and T3 (day 7) after surgery. The total length of stay in hospital of the two groups was also compared. Longer-term outcomes were further evaluated over three months at T4 (1 month) and T5 (3 months), and included the VAS pain level, STAI, sleep satisfaction, GSE and health-related quality of life (SF36).The intention-to-treat method was adopted. The process evaluation involved a qualitative study using telephone interviews. / Wong, Mi Ling, Eliza. / Adviser: Sally Chan. / Source: Dissertation Abstracts International, Volume: 71-01, Section: B, page: 0231. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2009. / Includes bibliographical references (leaves 256-278). / 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 Company, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese.

Sun, Minghui. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2011. / Includes bibliographical references (leaves 125-159). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.