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.

Tumour necrosis factor receptor associated factors (TRAFs) play a key role in signal transduction in mammalian cells. Several members of the TRAF family have been identified but only TRAF2 and TRAF6 are implicated in the regulation of both osteoclastic bone resorption and breast cancer. Here I studied the role of TRAF2 and TRAF6 in breast cancer induced osteoclastogenesis and osteolysis. I observed that TRAF2, but not TRAF6, is highly expressed in a highly metastatic bone-tropic clone of the human MDA-MB-231-BT (MDA-231-BT) breast cancer cells when compared to parental MDA-MB-231 (MDA-231) cells. Targeted knockdown of TRAF2, but not TRAF6, in both parental MDA-231 and bone-tropic MDA-231-BT breast cancer cells by siRNAs markedly reduced cell migration and significantly reduced the ability of these cells and their conditioned medium to induce osteoclast formation in RANKL stimulated bone marrow cultures. Encouraged by these data, I generated stable parental MDA-231 and bone-tropic MDA-231-BT breast cancer cell lines overexpressing TRAF2 using a retroviral approach. Then, I went on to show that overexpression of TRAF2 in parental MDA-231 cell line significantly stimulated directed cell migration and 3D invasion in vitro. Bone-tropic MDA-231-BT breast cancer cells over expressing TRAF2 or their conditioned medium were significantly effective in enhancing RANKL induced osteoclast formation in vitro. Mechanistic studies in parental MDA-231 and bone-tropic MDA-231-BT breast cancer cells revealed that over-expression of TRAF2 enhanced cell migration and osteoclastogenesis via a mechanism that involves the activation of the breast cancer oncogene IKKepsilon (IKKε) coupled with significant increase in levels of Vascular endothelial growth factor (VEGF). Ex vivo studies in human MDA-231-mouse calvaria organ co-cultures showed that conditioned medium obtained from MDA- 231 cells enhanced calvarial osteolysis. In vivo studies showed that overexpression of TRAF2 in the human breast cancer cells MDA-231 enhanced tumour incidence and tumour volume after orthotopic injection and exacerbated osteolysis after supracalvarial injection of conditioned medium from these cells. In conclusion, our studies showed that the TRAF2/IKK/VEGF axis in breast cancer cells regulates breast cancer cell motility in vitro, osteoclastogenesis in vitro and osteolysis ex vivo and in vivo. However, the role of TRAF2 in bone metastasis associated with breast cancer will require further in vivo investigation.

published_or_final_version / Medicine / Master / Doctor of Medicine

No description available.

Consumers and Canadian poultry processors were interviewed to understand the overall perception of bone-in chicken meat and to gain insight on the defect of black bone discoloration, a color defect that appears in cooked bone-in chicken. Through the consumer science technique of laddering, food safety, eating quality, price, health and convenience were revealed as the most important values associated with chicken meat. Poultry processors agreed upon the importance of food safety. Black bone discoloration did not greatly influence consumer acceptance of broiler meat, nor did it appear to negatively impact the poultry industry as complaints were reported rarely. Modifying broiler bone growth rate through dietary treatments did not significantly (P>0.05) alter the sensory properties of the meat or reduce the incidence of discoloration. Overall, black bone discoloration is not perceived as a major problem for the poultry industry in Canada. In order to maintain consumer demand, poultry producers should focus on the food safety aspect of their products. / Food Science and Technology

Diss. (sammanfattning) Umeå : Univ., 2003. / Härtill 5 uppsatser.

Thesis (M.S.)--University of Michigan, 1959.

Thesis (Ph. D.)--University of Hong Kong, 2007. / Title proper from title frame. Also available in printed format.

Thesis (doctoral)--Lund University, 1992. / Added t.p. with thesis statement inserted. Booklet of related papers inserted.

Thesis (doctoral)--Lund University, 1997. / Added t.p. with thesis statement inserted.