published_or_final_version / Biochemistry / Doctoral / Doctor of Philosophy

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.

published_or_final_version / Public Health / Master / Master of Public Health

Osteoporosis is a serious health problem worldwide and most commonly affects postmenopausal women (World Health Organization, 1994). Of the variety of complications associated with osteoporosis in postmenopausal women, osteoporotic fracture is the most prevalent and serious one. It affects their quality of life and puts heavy burden on the healthcare system in Hong Kong. Since osteoporosis exercise program can help to reduce bone loss, it seems to be an effective strategy to prevent and manage osteoporosis in postmenopausal women. The purpose of this study is to develop an evidence-based osteoporosis exercise education program for postmenopausal women, based on the best available evidence, with an aim of helping them to prevent and manage osteoporosis through the prevention and reduction of bone loss and its related fractures. A search of literature from four databases, including Pubmed (1997 to August 2011), CINAHL Plus (1937 to August 2011), Cochrane Library (1996 to Issue 8 of 2011) and EMBASE Classic + EMBASE (1947 to August 2011), was done to identify relevant randomized controlled trials (RCTs). The methodology checklist for RCTs developed by the Scottish Intercollegiate Guidelines Network (SIGN, 2008) was used to evaluate the quality of the selected studies. A total of nine studies met the inclusion criteria and did not violate the exclusion criteria. The findings of these studies showed that exercise intervention or program significantly reduced postmenopausal women’s likelihood of having fracture and also improved their bone mass density slightly. Among the reviewed studies, programs were most commonly implemented within a 12-month period and two 60-minute supervised exercise sessions were delivered per week. The potential of implementing the proposed program, based on the evidence from the literature review, to local practice was assessed. Based on the assessment, the proposed program is necessary and beneficial for postmenopausal women. An evidence-based osteoporosis exercise education program is developed based on the best available evidence. The SIGN grading system was utilized to provide grades for the recommendations in the guideline. An effective and adequate communication with potential stakeholders to gain their support and cooperation for the proposed program is essential. In addition, a tailor-made pilot test is also crucial for ensuring the successful implementation of the proposed program. The pilot study will be conducted in a local practice and the targeted participants are 124 postmenopausal women. Data analysis will be done by the paired t-test. The proposed evidence-based osteoporosis exercise education program will be considered as effective if (1) there is a reduction of bone loss and an increase in physical activity level in postmenopausal women, and (2) there is an increase of confidence and self-perceived skill on the prevention of management of osteoporosis in nurses. / published_or_final_version / Nursing Studies / Master / Master of Nursing

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.

Individuals who sustain a spinal cord injury (SCI) experience sublesional osteoporosis (SLOP) which affects the bones of the lower extremities. As a result, these bones become fragile and susceptible to fractures. To tackle SLOP pharmacological and rehabilitation interventions have been proposed; however few have produced a significant and sustainable increase in bone mineral density (BMD). This study investigated whole-body vibration (WBV) as an alternative to tackling SLOP in SCI. Two commercially available vibration platforms, WAVE® and Juvent™, were tested for feasibility and efficacy in the SCI population. The effects of knee angle, frequency and amplitude of vibration in propagation characteristics were also assessed. The results demonstrated that variations in frequency generate the most noticeable changes in propagation characteristics, followed by variations in knee angle and amplitude. The recommended vibration parameters which could potentially have the greatest osteogenic effect on the bones of the lower extremity are 160o, 45 Hz, and 0.6 mm on the WAVE® platform.

Individuals who sustain a spinal cord injury (SCI) experience sublesional osteoporosis (SLOP) which affects the bones of the lower extremities. As a result, these bones become fragile and susceptible to fractures. To tackle SLOP pharmacological and rehabilitation interventions have been proposed; however few have produced a significant and sustainable increase in bone mineral density (BMD). This study investigated whole-body vibration (WBV) as an alternative to tackling SLOP in SCI. Two commercially available vibration platforms, WAVE® and Juvent™, were tested for feasibility and efficacy in the SCI population. The effects of knee angle, frequency and amplitude of vibration in propagation characteristics were also assessed. The results demonstrated that variations in frequency generate the most noticeable changes in propagation characteristics, followed by variations in knee angle and amplitude. The recommended vibration parameters which could potentially have the greatest osteogenic effect on the bones of the lower extremity are 160o, 45 Hz, and 0.6 mm on the WAVE® platform.

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.

Postmenopausal osteoporosis is a disease characterized by bone loss and increased risk of fracture, and represents a significant burden on the Canadian health care system. Current treatments lack the ability to simultaneously address the therapeutic needs for promoting bone formation and inhibiting resorption. Our approach employs a novel conjugate drug in which an anabolic agent (EP4 receptor agonist) is reversibly joined with an anti-resorptive agent (alendronate) through a linker. This allows the bone-targeting ability of alendronate to deliver the EP4 agonist to bone sites, thereby mitigating the side effects associated with systemic administration of the EP4 agonist. This study investigated the in vivo efficacy of this drug in a curative experiment to treat postmenopausal osteoporosis using an ovariectomized rat model. Results showed that conjugate treatment dose-dependently stimulated bone formation and restored ovariectomy-induced bone loss, and conjugation between alendronate and the EP4 agonist was crucial to the drug’s anabolic effect.

Postmenopausal osteoporosis is a disease characterized by bone loss and increased risk of fracture, and represents a significant burden on the Canadian health care system. Current treatments lack the ability to simultaneously address the therapeutic needs for promoting bone formation and inhibiting resorption. Our approach employs a novel conjugate drug in which an anabolic agent (EP4 receptor agonist) is reversibly joined with an anti-resorptive agent (alendronate) through a linker. This allows the bone-targeting ability of alendronate to deliver the EP4 agonist to bone sites, thereby mitigating the side effects associated with systemic administration of the EP4 agonist. This study investigated the in vivo efficacy of this drug in a curative experiment to treat postmenopausal osteoporosis using an ovariectomized rat model. Results showed that conjugate treatment dose-dependently stimulated bone formation and restored ovariectomy-induced bone loss, and conjugation between alendronate and the EP4 agonist was crucial to the drug’s anabolic effect.