Bone defects resulting from non-unions, fractures, significant revision joint replacements, tumour resection and osteolysis present a clinical problem. While autografts are considered the gold standard, ubiquitous use of this reparative technique is limited by graft supply and site morbidity. Recent progresses in tissue engineering using stem cells, bone enhancing molecules and gene therapy have provided more hypotheses for bone defect treatment. In vivo assessment to test these hypotheses requires animal models to mimic human conditions. Immunodeficient or nude animals have the advantage of hosting materials from human and other xenographic origins without immuno-intolerance or rejection. A thorough understanding of the biology in nude animals is vital for the further advancement of connective tissue healing and regeneration strategies. Nude mice are excellent xenographic hosts for in- vivo characterisation and provide a reproducible animal source. The immune deficiencies of nude compared to normal animals may however, influence bone healing and need to be addressed. This dissertation (a) investigated potential bone defect models in nude mice and nude rats (b) incorporated the selected bone defect model to evaluate the effect of T cell deficiency and age on bone defect healing in nude animals (c) determined the feasibility of a critical size defect (CSD) in nude mice. A distal-femur-condylar-defect (DFCD) model was successfully performed in nude mice and rats. The model was found to have some advantages as a bone defect model: (1) located at a weight-bearing skeletal site (2) no requirements for an internal or external fixator (3) does not obstruct or limit mobility (4) location is not in close proximity to any major organs such as the brain (5) easy identification of surface anatomy (6) defect size is standardised and reproducible (7) does not require lengthy and complicated surgery and (8) cost effective. This dissertation confirmed that bone healing in nude mice is similar to that of normal immunocompetent mice. Absence of T lymphocytes did not delay or inhibit bone repair. Use of older nude mice did not seem to affect the healing rate, in contrast to older normal mice, which showed delay in bone healing in the initial phase. Establishment of critical sized defects in mice at a weight-bearing location was not feasible due to the robust healing of murine. This dissertation recommends that the DFCD model could be utilized for the assessment of xenogenic materials at early time point.

I have a background of active research in Radiation Oncology since passing the final examination of the Royal Australian and New Zealand College of Radiologists ( RANZCR ) at the first attempt in 1992. My first two papers were published the following year [ 1,2 - see curriculum vitae ], and there are currently 49 publications ( 26 first authorships ). My primary research interest has involved the use of radiotherapy ( RT ) for palliation of painful bone metastases. This interest originated from a year at Mt Vernon Hospital, UK, as the inaugural RANZCR Windeyer Fellow in Clinical Oncology ( 1993 ). I worked with Dr Peter Hoskin, a leading figure in the British Bone Pain Trial Working Party responsible for three randomised fractionation trials on this subject. These and many other previous and subsequent studies have demonstrated ( counter - intuitively ) that low dose single fraction RT is as effective as higher dose fractionated schedules in relieving bone pain, with intention - to - treat overall response rates ( RRs ) of about 60 %. However, the studies provided virtually no data on the efficacy of RT specifically for bone pain with a neuropathic component ( NBP ), a scenario occurring in perhaps as many as 20 % of patients with bone metastases during the course of their disease. On returning to Australia as a consultant radiation oncologist at the Royal Adelaide Hospital in 1994, I joined the Trans - Tasman Radiation Oncology Group ( TROG ), the major radiotherapy clinical trials group in Australasia. During the following year, I developed a protocol for a randomised controlled trial comparing one with five fractions of RT for NBP ( TROG 96.05 ). The first patient was registered in February 1996, and a total of 15 centres in Australia ( 11 ), New Zealand ( 3 ) and UK ( 1 ) took part. A National Health and Medical Research Council Project Grant of $ 172,000 was awarded for the study ( 1998-2000 ). Preliminary findings ( blinded to trial arm ) were published in 2000 [ 23 ], and extensive quality assurance activities for the trial were summarised in two further publications [ 21,38 ]. The accrual target was met in December 2002 ( n = 272 ) and the final analysis was reported as an oral presentation at the 12th European Cancer Congress, Copenhagen, September 2003. The essential findings were that NBP responds similarly to localised pain ( overall intention - to - treat RR 57 % ) with no statistically significant difference in RR or time to treatment failure between randomisation arms [ 43 ]. A subsequent cost analysis quantified the relative cost to the Australian healthcare system for the two fractionation schedules [ 47 ]. During the conduct of the trial, I undertook and published a survey confirming the reluctance of Australasian radiation oncologists to use single fractions for painful bone metastases despite the emerging randomised trial results [ 24 ]. I also contributed to the international debate on this controversial subject as co - author with three high profile researchers in a Letter - to - the - Editor [ 20 ], and was a member of an International Consensus Panel on palliative radiotherapy endpoints for future bone metastases trials [ Chow E et al. Radiother Oncol 2002 ; 64 : 275 - 80 ]. I presented invited lectures entitled : Fractionation regimens for metastatic bone pain ( RANZCR Scientific Meeting, Brisbane, 1998 ) ; Neuropathic pain and bone metastases ( Royal College of Radiologists Second Consensus Workshop in Palliative Radiotherapy and Symptom Control, London, 2000 ) [ 27 ] ; Radiotherapy for neuropathic bone pain : TROG 96.05 update ( International Congress of Radiation Oncology, Melbourne, 2001 ) [ 30 ]. My recognised expertise in this field also led to invitations to write an Editorial on the published overviews of bone pain studies [ 40 ], and a book chapter on bone metastases from lung cancer [ 49 ]. My active role in bone pain research continues. The abovementioned International Consensus Panel collaboration led to the development of the first randomised trial on re - treatment of bone metastases with RT. This National Cancer Institute of Canada sponsored international Intergroup trial ( NCIC SC.20 / TROG 03.08 ) has an accrual target of 650 patients and was activated in January 2004. I am the Australasian Co - Chair, securing $ 40,000 funding for local capitation from Cancer Council Australia in February 2004. I believe this body of work constitutes a significant contribution to the literature on RT for bone metastases, and NBP in particular. My research on the latter constitutes the first prospective data ever obtained on RT for this clinical problem, enabling informed selection of single or multiple fraction treatment schedules. / Thesis (M.D.)--Department of Medicine, 2005.

The morphology and function of the wrist is poorly understood. Improved understanding of carpal anatomy may facilitate improved understanding of carpal mechanics and may enhance the clinical management of wrist dysfunction. Many detailed investigations of wrist structure have been reported, many of which have focussed on the scaphoid and its ligamentous supports. The results of these studies are not readily collated to provide an accurate description of the scaphoid and its supports. This study attempted to provide a detailed description of the anatomy of the scaphoid and its supporting structures. A detailed nomenclature was proposed to facilitate accurate description of the scaphoid and related structures. Gross observation enabled separation of the sample population of scaphoids into two groups. Morphometric analyses were used to determine any significant differences between the groups (type one and type two). The histological sections were then used to facilitate accurate gross identification of ligaments and computed tomographs were used to investigate the in situ variation of scaphoid orientation. The investigations suggest that two distinct populations of scaphoid existed within the sample population. The scaphoids varied in bone morphology, arrangement and degree of ligamentous support and position relative to the capitate. Articular facet shape and size differed between scaphoid types. The orientation and number of ligaments supporting the scaphoid were suggestive of variable scaphoid motion. The variation in ligamentous patterns was supported by histological investigation. Computed tomographs through the longitudinal axis of the scaphoid suggested a variable position of the scaphoid relative to the capitate. The variation of these structures was discussed in relation to the kinematic findings of others. A theoretical model of variable scaphoid function was proposed based on the anatomical findings. The data presented and the reviewed kinematic data may be extrapolated to suggest two models of scaphoid motion. The scaphoids may be divided into rotating/translating scaphoids and flexing/extending scaphoids. This must be confirmed by a combined anatomical and mechanical study. The clinical implications of different scaphoid structure and function may be profound. The ability to identify such differences in situ may facilitate varied clinical management for the various types of wrist suggested. / Thesis (Ph.D.)--Department of Anatomical Sciences, 2004.

Thesis (M.D.S.)--University of Hong Kong, 1998. / Includes bibliographical references. Also available in print.

Thesis (Ph. D.)--State University of New York at Binghamton, Anthropology Dept., 2006. / Includes bibliographical references.

Bone defects resulting from non-unions, fractures, significant revision joint replacements, tumour resection and osteolysis present a clinical problem. While autografts are considered the gold standard, ubiquitous use of this reparative technique is limited by graft supply and site morbidity. Recent progresses in tissue engineering using stem cells, bone enhancing molecules and gene therapy have provided more hypotheses for bone defect treatment. In vivo assessment to test these hypotheses requires animal models to mimic human conditions. Immunodeficient or nude animals have the advantage of hosting materials from human and other xenographic origins without immuno-intolerance or rejection. A thorough understanding of the biology in nude animals is vital for the further advancement of connective tissue healing and regeneration strategies. Nude mice are excellent xenographic hosts for in- vivo characterisation and provide a reproducible animal source. The immune deficiencies of nude compared to normal animals may however, influence bone healing and need to be addressed. This dissertation (a) investigated potential bone defect models in nude mice and nude rats (b) incorporated the selected bone defect model to evaluate the effect of T cell deficiency and age on bone defect healing in nude animals (c) determined the feasibility of a critical size defect (CSD) in nude mice. A distal-femur-condylar-defect (DFCD) model was successfully performed in nude mice and rats. The model was found to have some advantages as a bone defect model: (1) located at a weight-bearing skeletal site (2) no requirements for an internal or external fixator (3) does not obstruct or limit mobility (4) location is not in close proximity to any major organs such as the brain (5) easy identification of surface anatomy (6) defect size is standardised and reproducible (7) does not require lengthy and complicated surgery and (8) cost effective. This dissertation confirmed that bone healing in nude mice is similar to that of normal immunocompetent mice. Absence of T lymphocytes did not delay or inhibit bone repair. Use of older nude mice did not seem to affect the healing rate, in contrast to older normal mice, which showed delay in bone healing in the initial phase. Establishment of critical sized defects in mice at a weight-bearing location was not feasible due to the robust healing of murine. This dissertation recommends that the DFCD model could be utilized for the assessment of xenogenic materials at early time point.

Bone defects resulting from non-unions, fractures, significant revision joint replacements, tumour resection and osteolysis present a clinical problem. While autografts are considered the gold standard, ubiquitous use of this reparative technique is limited by graft supply and site morbidity. Recent progresses in tissue engineering using stem cells, bone enhancing molecules and gene therapy have provided more hypotheses for bone defect treatment. In vivo assessment to test these hypotheses requires animal models to mimic human conditions. Immunodeficient or nude animals have the advantage of hosting materials from human and other xenographic origins without immuno-intolerance or rejection. A thorough understanding of the biology in nude animals is vital for the further advancement of connective tissue healing and regeneration strategies. Nude mice are excellent xenographic hosts for in- vivo characterisation and provide a reproducible animal source. The immune deficiencies of nude compared to normal animals may however, influence bone healing and need to be addressed. This dissertation (a) investigated potential bone defect models in nude mice and nude rats (b) incorporated the selected bone defect model to evaluate the effect of T cell deficiency and age on bone defect healing in nude animals (c) determined the feasibility of a critical size defect (CSD) in nude mice. A distal-femur-condylar-defect (DFCD) model was successfully performed in nude mice and rats. The model was found to have some advantages as a bone defect model: (1) located at a weight-bearing skeletal site (2) no requirements for an internal or external fixator (3) does not obstruct or limit mobility (4) location is not in close proximity to any major organs such as the brain (5) easy identification of surface anatomy (6) defect size is standardised and reproducible (7) does not require lengthy and complicated surgery and (8) cost effective. This dissertation confirmed that bone healing in nude mice is similar to that of normal immunocompetent mice. Absence of T lymphocytes did not delay or inhibit bone repair. Use of older nude mice did not seem to affect the healing rate, in contrast to older normal mice, which showed delay in bone healing in the initial phase. Establishment of critical sized defects in mice at a weight-bearing location was not feasible due to the robust healing of murine. This dissertation recommends that the DFCD model could be utilized for the assessment of xenogenic materials at early time point.

Thesis (Ph.D.)--University of Hong Kong, 2000. / Includes bibliographical references (leaves 131-154) Also available in print.

Thesis (Ph. D.)--University of Washington, 1982. / Vita. Bibliography: leaves 235-255.

Introduction: The process by which children's bones grow has not been fully charcterised. The current dogma is that girls fill in their medullary canal area by forming bone at the endosteum. It has been argued that the sex difference in how bone strength is conferred -- favouring boys -- may contribute to the relative protection that aging men have over aging women with respect to fracture incidence and the prevalence of osteoporosis. Primary Objectives: 1)To compare bone surface changes at the periosteal and endosteal surface of the tibial midshaft in boys and girls. 2)To compare how bone density at the tibial midshaft is accrued in boys and girls. 3) To compare sex differences in bone strength accrual. Methods: Design and Participants: Participants were obtained from a 20-month randomized, controlled school-based physical activity intervention. As we found no difference in the effect of the intervention on pQCT bone outcome variables, both groups were combined for our current study. A total of 183 participants (93 boys, 89 girls) received a pQCT scan at baseline. Results: Sex-specific comparisons of the pQCT bone outcome variables showed significantly greater rates of change (slope) for boys for the total area (ToA), cortical area (CoA), medullary canal area (MedA) and strength-strain index (SSI) measures, p<0.001. No significant differences were observed for CoD, p=0.904. The magnitude of these differences is 60.8% for ToA, 55.7% for CoA, 75.6% for MedA, 1.3% for CoD, and 54.7% for SSI. Examination of differences between the sexes (intercept) revealed significant differences with greater gains observed for boys for all measures p<0.001 except for CoD where girls exhibited greater gains p<0.001. Conclusion: Girls showed a similar pattern of cortical bone growth at the tibial midshaft- periosteal apposition dominated over endosteal resorption. Boys' increased changes and pattern of growth were of a greater magnitude at both surfaces compared to girls. This resulted in a greater increase in strength as measured by SSI in boys which can partly be explained by their larger size. Girls exhibited greater increases in CoD; however, no significant difference in the change in CoD was observed between the two.