Thesis (Ph.D.)--University of Hong Kong, 1998. / Includes bibliographical references (leaves 213-248) Also available in print.

Thesis (M.S.)--University of Akron, Dept. of Biomedical Engineering, 2006. / "December, 2006." Title from electronic thesis title page (viewed 06/27/2007) Co-Advisors, Glen O. Njus, Daniel B. Sheffer; Faculty Reader, Mary C. Verstraete; Department Chair, Daniel B. Sheffer; Dean of the College, George K. Haritos; Dean of the Graduate School, George R. Newkome. Includes bibliographical references.

No description available.

Cancellous bone constitutes much of the volume of bone which makes up axial skeletal sites such as the vertebrae of the spine and the femoral neck. However the increased vascularity of cancellous bone compared with cortical bone means that it is more prone to drug, endocrine and metabolic related effects and therefore these skeletal sites are more prone to the bone condition osteoporosis. With the bone condition osteoporosis increasing in prevalence it is becoming far more important not only for those at risk of having the condition to be diagnosed earlier, but also for the effects of the condition to be better understood. There is a need for the better clinical management of fractures and for therapies and medical practices that will best avoid the low trauma fractures that are seen as a consequence of the condition. This study is in two separate sections, the first constitutes an investigation into the diagnostic abilities of the CUBA Clinical and Sunlight Omnisense quantitative ultrasound systems; and on the other hand an examination of the osteoporotic risk factor questionnaires, Osteoporosis Risk Assessment Instrument (ORAI), Osteoporosis Index of Risk (OSIRIS), Osteoporosis Self-assessment Tool (OST), Patient Body Weight (pBW), Simple Calculated Osteoporosis Risk Estimation (SCORE) and the Study of Osteoporotic Fractures (SOFSURF). The skeletal status was assessed by DXA at the axial skeleton. The aim was to differentiate between the systems that could rationally be used to screen populations to identify those who needed DXA densitometry investigations, on the basis of ability. The second section of the study focused on the biomechanics of cancellous bone, with the initial studies examining the compressive properties of both osteoporotic and osteoarthritic cancellous bone and the effects that the conditions have on the compressive mechanics of the bone. The later section is the first ever study into the K, G and J-integral fracture mechanics of cancellous bone. It used osteoporotic and osteoarthritic cancellous bone from the femoral head of a cohort of ultrasound scanned patients and of some equine vertebral cancellous bone. The study focused on the identification of the dominant independent material variables which affected the compressive and fracture mechanics of cancellous bone, and the differences that were seen between the two different skeletal conditions. In addition to the independent variables, quantitative ultrasound (QUS) scans were performed on the donors of the femoral heads which enabled investigation into QUS’s ability to predict either the compressive or fracture mechanics of bone in-vivo. The study demonstrated that the investigation of the calcaneus using the CUBA clinical system provided the highest level of diagnostic accuracy (AUC: 0.755 - 0.95), followed by the questionnaires, of which the OSIRIS questionnaire was the best performer (AUC: 0.74 – 0.866), and lastly the Sunlight Omnisense results. The best option for the prediction of the lowest feasible DXA T-score was a combination of the CUBA Clinical results, the individual’s weight and the OSIRIS questionnaire (r2 = 45.5%), with potential minor, but significant, support also added by the OST and SOFSURF questionnaires (r2 = 46.8%). The compressive testing demonstrated that osteoporotic and osteoarthritic bone both performed differently with respect to the apparent density, with the osteoporotic bone adhering to the previously published power function relationships, but with the osteoarthritic bone having lower power functions. The stress intensity factor for plane strain testing (KQ or KC) and the critical strain energy release rate results were both influenced primarily by the apparent density with the K values obeying a power relationship to the power of 1.5 and G a relationship to the power 2. However, both the composition and integrity of the collagen network, (demonstrated by collagen cross-link analysis), played roles in the explanation of the fracture mechanics results. The J-integral results were distinctly different to those of the K and G results with regard to their dependence on composition and it is hypothesised that this is due to the structure of the bone having more dominant effects than the apparent density. In conclusion, the fracture mechanics of cancellous bone are contributed to by a complex combination of a number of variables, but with apparent density dominating the K and G fracture mechanics to a power function of between 1 and 2. Currently available QUS systems demonstrated an ability to relate to the Young’s modulus and strength but also, in this study, to the fracture mechanics variables of the cancellous bone from the hip. This relationship is a profound outcome which may help the clinical management of the condition and the fractures when they occur. The dependence on fracture mechanic variables points to a clear causal relationship between the bone fracture parameters and bone condition as underlying factors of osteoporotic fractures.

Cancellous bone constitutes much of the volume of bone which makes up axial skeletal sites such as the vertebrae of the spine and the femoral neck. However the increased vascularity of cancellous bone compared with cortical bone means that it is more prone to drug, endocrine and metabolic related effects and therefore these skeletal sites are more prone to the bone condition osteoporosis. With the bone condition osteoporosis increasing in prevalence it is becoming far more important not only for those at risk of having the condition to be diagnosed earlier, but also for the effects of the condition to be better understood. There is a need for the better clinical management of fractures and for therapies and medical practices that will best avoid the low trauma fractures that are seen as a consequence of the condition. This study is in two separate sections, the first constitutes an investigation into the diagnostic abilities of the CUBA Clinical and Sunlight Omnisense quantitative ultrasound systems; and on the other hand an examination of the osteoporotic risk factor questionnaires, Osteoporosis Risk Assessment Instrument (ORAI), Osteoporosis Index of Risk (OSIRIS), Osteoporosis Self-assessment Tool (OST), Patient Body Weight (pBW), Simple Calculated Osteoporosis Risk Estimation (SCORE) and the Study of Osteoporotic Fractures (SOFSURF). The skeletal status was assessed by DXA at the axial skeleton. The aim was to differentiate between the systems that could rationally be used to screen populations to identify those who needed DXA densitometry investigations, on the basis of ability. The second section of the study focused on the biomechanics of cancellous bone, with the initial studies examining the compressive properties of both osteoporotic and osteoarthritic cancellous bone and the effects that the conditions have on the compressive mechanics of the bone. The later section is the first ever study into the K, G and J-integral fracture mechanics of cancellous bone. It used osteoporotic and osteoarthritic cancellous bone from the femoral head of a cohort of ultrasound scanned patients and of some equine vertebral cancellous bone. The study focused on the identification of the dominant independent material variables which affected the compressive and fracture mechanics of cancellous bone, and the differences that were seen between the two different skeletal conditions. In addition to the independent variables, quantitative ultrasound (QUS) scans were performed on the donors of the femoral heads which enabled investigation into QUS’s ability to predict either the compressive or fracture mechanics of bone in-vivo. The study demonstrated that the investigation of the calcaneus using the CUBA clinical system provided the highest level of diagnostic accuracy (AUC: 0.755 - 0.95), followed by the questionnaires, of which the OSIRIS questionnaire was the best performer (AUC: 0.74 – 0.866), and lastly the Sunlight Omnisense results. The best option for the prediction of the lowest feasible DXA T-score was a combination of the CUBA Clinical results, the individual’s weight and the OSIRIS questionnaire (r2 = 45.5%), with potential minor, but significant, support also added by the OST and SOFSURF questionnaires (r2 = 46.8%). The compressive testing demonstrated that osteoporotic and osteoarthritic bone both performed differently with respect to the apparent density, with the osteoporotic bone adhering to the previously published power function relationships, but with the osteoarthritic bone having lower power functions. The stress intensity factor for plane strain testing (KQ or KC) and the critical strain energy release rate results were both influenced primarily by the apparent density with the K values obeying a power relationship to the power of 1.5 and G a relationship to the power 2. However, both the composition and integrity of the collagen network, (demonstrated by collagen cross-link analysis), played roles in the explanation of the fracture mechanics results. The J-integral results were distinctly different to those of the K and G results with regard to their dependence on composition and it is hypothesised that this is due to the structure of the bone having more dominant effects than the apparent density. In conclusion, the fracture mechanics of cancellous bone are contributed to by a complex combination of a number of variables, but with apparent density dominating the K and G fracture mechanics to a power function of between 1 and 2. Currently available QUS systems demonstrated an ability to relate to the Young’s modulus and strength but also, in this study, to the fracture mechanics variables of the cancellous bone from the hip. This relationship is a profound outcome which may help the clinical management of the condition and the fractures when they occur. The dependence on fracture mechanic variables points to a clear causal relationship between the bone fracture parameters and bone condition as underlying factors of osteoporotic fractures.

Osteoporosis and osteopenia are long-term side effects of bone marrow transplant (BMT). The purpose of this study was to determine the prevalence of bone mineral density (BMD) abnormalities in pediatric patients prior to BMT. Forty-four pediatric patients were evaluated with DEXA scans. The average Z-score was -0.37. Thirty-six percent had abnormal BMD. Sixty-seven percent of ALL patients had abnormal BMD. Patients with non-malignant diseases were significantly more likely to have abnormal BMD. Patients with ALL had more defects than solid tumor patients. Females had more defects than males. These results demonstrate BMD defects are common in children prior to BMT, especially in patients with ALL.

Osteoporosis is a disease that may be pre-determined from the condition of bone health during youth. In South Africa, the situation is quite unique in that the population of black people has a reduced fracture rate compared to white people. As lifestyle and dietary patterns change with urbanisation and there is a shift towards westernised diets and sedentary behaviour in youth, fractures in elderly South African blacks may become more prevalent. With these rapid lifestyle changes, it will become increasingly important to prioritise osteoporosis and its related conditions as a major public health concern in South Africa. Very few of the factors influencing osteoporosis have been well studied in children of different ethnic groups. Physical activity in childhood, especially in the prepubertal years, confers residual benefits to the adult skeleton. In this thesis, the associations between ethnicity, history of participation in physical activity and skeletal health were explored in a sample of pre-/early pubertal children from South Africa who participated in four different studies. Furthermore, a novel aspect of the thesis was the use of peripheral quantitative computed tomography (pQCT) to investigate the mechanistic role that physical activity plays on bone health in this unique population. First the use of an existing physical activity questionnaire for the assessment of bone loading had to be validated in a sample of black and white boys and girls (n=38). A bone loading algorithm was used to calculate a peak bone strain score (PBSS) from the physical activity questionnaire. Therefore a bone specific physical activity questionnaire (B3Q) was used in subsequent studies. The PBSS was shown to be reliable and reproducible with significant (p<0.001) intraclass correlation coefficients. There were significant correlations between PBSS and moderate (r=0.38; p=0.02), vigorous (r=0.36; p=0.03) and combined moderate to vigorous intensity activity counts (r=0.38; p=0.02) as measured by accelerometry. The ability of the PBSS algorithm to classify children into high or low weight bearing groups was in moderate agreement with accelerometer derived combined moderate and vigorous activity counts (κ=0.42; p=0.008). PBSS was significantly correlated to body size adjusted bone mineral content at all sites scanned by DXA (r=0.43-0.57; p<0.05). Positive correlations were observed between PBSS and area, density and strength at the radius and tibia (r=0.40-0.64; p<0.05). At the radial metaphysis, significant correlations between moderate activity (r=0.46; p=0.005) and combined moderate and vigorous activity counts (r=0.42; p=0.01) were seen for bone strength. No associations were seen between accelerometer measured physical activity and bone outcomes at the tibial diaphysis. Multiple regression analysis showed that the PBSS was a better predictor of bone mass and structure than was accelerometry. The next study sought to determine whether children who were classified as being high bone loaders for the past two years would present with greater bone mass and strength regardless of their ethnicity. Sixty six children [black boys, 10.4(1.4) yrs, n=15; black girls, 10.1(1.2) yrs, n=27; white boys, 10.1(1.1) yrs, n=7; white girls, 9.6(1.3) yrs, n=17] reported on all their physical activities over the past two years in the interviewer administered bone specific physical activity questionnaire (B3Q). Children were classified as being either high or low bone loaders based on the cohort’s median peak bone strain score estimated from the B3Q. In the low bone loading group, black children had greater femoral neck bone mineral content (BMC) (2.9 (0.08)g) than white children (2.4 (0.11)g; p=0.05). There were no ethnic differences in the high bone loaders for femoral neck BMC. At the cortical sites, the black low bone loaders had a greater radius area (97.3 (1.3) vs 88.8 (2.6) mm2 ; p=0.05) and a greater tibia total area (475.5 (8.7) vs. 397.3 (14.0) mm2 ; p=0.001) and strength (1633.7 (60.1) vs. 1271.8 (98.6) mm3 ; p=0.04) compared to the white low bone loaders. These measures were not different between the black low and high bone loaders or between the black and white high bone loaders. Ethnic differences in bone area and strength apparent between children classified as having a lower bone loading physical activity history appear to have been attenuated when children partaking in high bone loading physical activities were compared. Greater levels of mechanical loading seemed to have no apparent benefits in black children. Cross-sectional studies in black and white pre-pubertal children have observed significant ethnic differences in structural bone outcomes as measured by pQCT but there are a limited number of intervention studies that have been conducted in black children. The cortical bone of black and white children may respond differently to mechanical forces, yet no physical activity interventions and their effects on bone structure in black children have been done. The aim of the third study was to determine whether a weight-bearing physical activity intervention improves measures of bone mass, structure and strength in pre-pubertal black children. Children (9.7 ± 1.1 years) were randomised into an exercise (EX; n=12) and control (CON; n=11) group. The EX children performed a 20-week weightbearing exercise program performed twice a week for 45 minutes per session, while CON children continued their regular activities. Changes in tibial trabecular volumetric bone density, area and strength were greater in the EX than the CON group (all p<0.01). At the cortical site of the tibia, the change in bone density was greater in the EX group than the CON group (all p<0.05). The greater change in tibial periosteal circumference in the EX groups also resulted in a greater change in cortical thickness of the tibia compared to the CON group (p<0.05). The final study assessed whether rates of bone accrual differed over one year between high and low bone loaders and also between black and white South African children. Forty seven children (18 boys, 29 girls) were followed up after one year. High bone loaders tended to have greater baseline BMC at all sites measured by DXA but the difference was only significant at the femoral neck (p=0.03). At the follow up visit, femoral neck BMC remained significantly higher in the high compared to the low bone loaders (p=0.003). Bone strength index (BSI) at the follow up visit was significantly greater in the high bone loaders compared to the low bone loaders (p=0.05). Although there was a trend for the high bone loaders to have greater indices of density and area at the 65% tibia compared to the low bone loaders, this was not significantly different at baseline or at follow up. High bone loaders had greater relative changes in whole body BMC (p=0.002), tibial cortical area (p=0.03), cortical density (p=0.04) and cortical thickness (p=0.03) compared to low bone loaders. There were no significant differences in DXA bone outcomes between black and white children at baseline and follow up. At baseline, total density at the 4% radius was greater in black than in white children (p<0.001) but total density at the follow up visit was not significantly different between black and white children (p=0.06). Trabecular density was greater in the black than in the white children at baseline (p=0.01) as well as at follow up (p=0.04). BSI at baseline was greater in the black than in the white children (p=0.05) but this significance disappeared at follow up. Similar to the 4% radius, cortical density at baseline was significantly greater in the black compared to the white children at the 65% radius (p=0.01) and at the 65% tibia (p=0.04). In conclusion, the PBSS algorithm from the B 3Q can be used to reliably and accurately collect data on previous participation in weight bearing exercise and is able to classify children as being either high or low bone loaders. It appears that in order for White children to reach the same bone mass/health levels as Black children, they may need to participate in higher levels of weight-bearing physical activity. Ethnic differences in bone area and strength apparent between children classified as having a lower bone loading physical activity history appear to have been attenuated when children partaking in high bone loading physical activities were compared. The associations may indicate that a strong environmental influence (i.e. high participation in physical activity) may offer similar or even superior benefits to bone over genetic (ethnic) influences. The use of pQCT appears to be sufficiently sensitive in detecting bone structural changes in response to mechanical loading interventions. As such, pQCT measures were able to determine the efficacy of a weight bearing physical activity intervention on trabecular and cortical sites in black children, and, similar to what has previously been observed in white and Asian children, our knowledge on the attainment of bone in response to an exercise intervention in black children is deepened. Moreover, the bone accrual that occurs in a population of black and white children from a low-middle income country may also differ between ethnicities and may reflect an environmental influence that modifies existing paradigms on physical activity and bone health in children. The promotion of weightbearing physical activity should occur in all youth, to oppose the possible lifestyle induced risks for developing osteoporosis in adulthood.

Original published work submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, in fulfilment of the requirements for the degree of Doctor of Philosophy, August 2019 / Age-at-death estimates in skeletal remains are hampered by observer bias and error, as well as individual and population variation. This study aimed at improving accuracy and reliability of age estimates obtained from applying methods involving the assessment of histomorphometric variables of bone and bone mineral density (BMD). The assessment of osteon population density (OPD) and size (length, surface area and volume) of Haversian systems were investigated in three populations by means of stereology. Bone slides prepared from South African black (n = 99), South African white (n = 94) and Danish white (n = 30) individuals were analysed using MicroBrightField’s StereoInvestigator software. ANCOVA results revealed a statistically significant difference (p < 0.001) between the three groups in terms of OPD. No statistically significant difference was seen in the size of secondary osteons between the groups. Linear regression analysis was used to construct population-specific formulae for age-atdeath estimation in South African white and black individuals. The Danish sample was used as a comparative group for white South African standards established. Age mimicry appeared to play a role in the over-estimation of age in the Danish individuals, after which the problem was corrected by combining the two samples in order to achieve normal age distribution within the larger sample. Secondly, DXA scans of the proximal femur were done for a subgroup of South African black (n = 64) and white (n = 59) individuals for estimation of age-at-death from bone mineral density. Results displayed a significant difference between white and black groups for total and neck BMD. White males and females differed in total and neck BMD, although black males and females differed only in terms of neck BMD. Age could be significantly correlated with BMD in the white population, but not in the black population. Regression analysis was also done for the complete sample (white and black individuals pooled), as ancestry is unknown in some cases. A significant correlation was seen for age versus neck BMD in the total sample and in sex-specific groups. The outcome of this study suggested that the three population samples are somewhat dissimilar in bone microstructure, with differences related to OPD and BMD present between the groups. Based on this outcome, it should be emphasized that age estimation standards should be adapted to accommodate combined groups and create to more generally applicable standards. Further research involving various disciplines is needed to better understand the underlying reason(s) for these differences between these populations. / PH2020

Indiana University-Purdue University Indianapolis (IUPUI) / Fluoride has been used in the treatment of osteoporosis because of its apparent ability to directly initiate bone formation. However, fluoride's therapeutic efficacy is controversial. Clinical trials in the range of 50 to 75 mg/day demonstrated severe side effects and a lack of consistent therapeutic benefits. Animal studies have not fully proven a positive effect of fluoride on bone strength. The objective of this study was to determine the histomorphometric changes in the cortical bone of rabbits caused by high doses of fluoride. The hypothesis was that high-dose fluoride intake enhances bone modeling and inhibits bone remodeling. Twenty-four young adult (four months old) female, Dutch Belted rabbits were randomly divided in two groups. The control group received no fluoride in their drinking water, while the experimental group received 100-ppm fluoride. Both groups received approximately 12-ppm fluoride in their food. A pair of tetracycline labels was given two weeks apart before initiation of the experiment. Fluoride treatment was given for six months. A terminal pair of calcein green labels was given before the animals were euthanized. Histomorphometric measurements were made using stereological point-hit and linear-intercept methods. The histomorphometric findings were correlated with fluoride serum and bone levels and also with strength tests. The study demonstrated that fluoride increases bone modeling by increasing periosteal bone apposition and endosteal bone resorption. The net effect of fluoride was an enlargement of the cortical bone and bone marrow and, therefore, the total tissue cross-section. However, the observed increase in bone mass produced by fluoride did not have a positive effect on the mechanical properties of bone. Fluoride did not produce a change in the primary histomorphometric parameters of osteoid surface (OS/BS%) or mineralizing surface (MS/BS%). Fluoride treatment produced an increase in the cortical periosteal modified mineral apposition rate (CPMAR). The remaining dynamic indices (i.e. endosteal MAR, remodeling MAR, cortical endosteal BFR and total BFR, activation frequency and formation period) were not affected by fluoride. The study failed to show an inhibitory effect of fluoride on bone remodeling.

No description available.