Sex differences in bone mass and size are thought to contribute to the greater incidence of vertebral fractures in women. While these sex differences are widely recognized, the relative contributions of bone mass, bone density, and bone size to the differences in vertebral strength and fracture risk between men and women have not been fully delineated. Furthermore, it is unknown whether the roles of each of these factors in determining vertebral strength change differently with age in men and women. We studied the bone content, density and geometry as well as vertebral loading and the factor of risk of the L3 vertebra in a sample of prepubertal males and females. Our first aim was to assess differences in vertebral bone dimensions, bone density, vertebral loading patterns and fracture risk, as measured by the factor of risk, in prepubertal children. Our second aim was to determine whether pre-pubertal growth affects the geometry and density of L3 differently in boys and girls. We measured vertebral dimensions, cross-sectional area and volumetric BMD of the third lumbar vertebral body in 93 prepubertal children (54 boys and 39 girls), using dual-energy X-ray absorptiometry scans obtained in the posterior-anterior and lateral projections. We also employed basic biomechanics to estimate vertebral loading during upright standing and forward bending. Bone strength and loading data were used to assess sex differences in the factor of risk in prepubertal children. Twenty children (11 boys and 9 girls) were assessed at baseline and seven months later to examine the effects of growth on bone size and vBMD. At baseline, boys and girls were similar for age, height, weight and calcium intake. L3 width and depth were 6.7% and 5.8% greater in boys than girls, respectively (P<0.001 and P=0.01, respectively). In contrast, vertebral height was 3.5% greater in girls than boys (P= 0.04). While vertebral loading was similar between sexes, stresses on the spine were 12.2% lower in boys during upright standing and 12.0% lower in boys during forward bending at both 50° and 90°, as compared to girls (P<0.001, P<0.01 and P<0.01, respectively). The factor of risk was similar between boys and girls under each loading condition. During growth, changes in vertebral size and density were not different between boys and girls. Our results indicate that even prior to puberty, sex differences in vertebral size contribute to differences in vertebral stress during standing and forward bending. Furthermore, before the onset of puberty, growth does not result in disparate changes between sexes. / Graduation date: 2004

Studies in young women show that rowing exercise is osteogenic at the spine. However, little is known regarding rowing exercise and spine bone mineral density in older women. The aim of this study was to examine differences in spine bone mineral density (BMD) and back strength between premenopausal and postmenopausal competitive female masters rowers (n=28, 45.5 ± 4.7 yrs, n=28, 56.1 ± 5.7 years, respectively) and age-matched non-rowers (n=30, 43.3 ± 4.2 yrs; n=26, 56.8 ± 4.8 years). Competitive rowers were recruited from nine rowing clubs in the local area and compared to controls recruited from the same region who were normally active but not participating in rowing activity. Participating rowers had been engaged in competitive rowing for a minimum of one year. The average years spent rowing for the premenopausal and postmenopausal groups was 7.5 ± 6.6 yrs and 5.9 ± 6.9 yrs, respectively. BMD (g/cm²) of the third lumbar vertebrae (L3) was measured by dual-energy x-ray absorptiometry (DXA) in both the anterior-posterior and lateral views. Back strength was assessed using a standing cable tensiometer. Subjects also completed questionnaires to assess diet, physical activity, medical history and rowing history. Differences in BMD and back strength between groups were determined by analysis of covariance, controlling for lean mass. Compared to controls, postmenopausal rowers had 3.2% higher BMD at the anterior-posterior spine (p=.02) and 4.4% higher lateral spine BMD (p=.04). Furthermore, isometric back strength was 22.6% greater in these rowers than controls (p=.01). In contrast, controls had higher lateral BMD than rowers, with no differences in AP spine BMD or back strength between the premenopausal rowers and controls. Back strength was a significant predictor of AP spine BMD in premenopasual rowers and controls (R²=0.137, p=0.004) and of lateral spine BMD in postmenopausal rowers only (R²=0.153, p=0.04). There were no differences in calcium intake, age, menopausal status, weight, or lean mass between rowers and controls in either the premenopausal or postmenopausal samples. Since both increased BMD and back strength are associated with reductions in vertebral fracture risk, our results suggest that rowing exercise may be an important strategy to promote bone health and reduce vertebral fracture risk in postmenopausal women. However, the forces applied in rowing may not be great enough to alter bone mass before the onset of menopause. Therefore more research is needed examining rowing exercise in these older populations. / Graduation date: 2005

Discordance in bone mass between young adult swimmers and soccer players may be a direct result of differences in bone loading patterns that influence bone mineralization during growth. Our aim was to evaluate whether sports participation (soccer and swimming) had an independent effect on bone mass accrual at the hip and lumbar spine in adolescent female athletes. We recruited boys and girls 10 to 14-years of age from Corvallis, Albany, Sweet Home, Salem, Eugene, and the greater Portland area. Bone mineral content (BMC, g) and bone mineral density (BMD, g/cm²) of the proximal left hip, spine, and whole body were assessed by dual energy x-ray absorptiometry (Hologic QDR 4500A; Hologic Inc., Waltham, MA, USA). We used ANCOVA and report that baseline BMC and BMD values of girl soccer players at the greater trochanter were significantly higher compared to controls and the swim group, and femoral neck BMC was significantly greater than the swimmers. At baseline, all boy groups were similar at the hip and spine. After 12-months, ANCOVA was also used to assess absolute change for BMC and BMD at the hip and spine. The girl soccer players had significantly more BMC and BMD at the greater trochanter as well as total hip BMD and lumbar spine BMC compared to the swimmers, but not the controls. The girl control group showed a significantly greater 12-month change for femoral neck and greater trochanter BMC than swimmers. Overall, the girl swimmers demonstrated a lower accumulation of bone mass during the 12-month study period. As for the boys, soccer players had a significantly higher 12-month change for femoral neck BMC than swimmers, but were similar at the spine. There were no differences between the boy control subjects and the swimmers for 12-month change values at the hip and spine. While preliminary and limited by the small sample size, our results indicate that after controlling for growth, soccer players gained significantly more BMC at the femoral neck than swimmers. Furthermore, exposing the young skeleton to impact loading exercise has site-specific benefits at the hip whereas prolonged training in a non-weight bearing environment may compromise skeletal acquisition. / Graduation date: 2004

In the United States, falls are the leading cause of unintentional death with one of every three people 65 years and older falling each year. Falls account for approximately 95% of hip fractures among older adults and falls to the side predominate hip fracture related falls in this population. However, risk factors for side and frequent falls are poorly understood. Furthermore, few data exist to explain differences in bone mineral density among older postmenopausal women. In particular, data regarding the timing of hormone replacement therapy (HRT) among older women is scarce. In the first aim of this dissertation, we examined changes in mobility and balance-related risk factors for side falls as well as differences in these risk factors according to fall status in a population of 107 independent, elderly women (>70 yrs), who were followed over 2 years. We found hip abduction strength decreased (p<.001) in all subjects, with side-fallers exhibiting weaker hip abduction strength (p=.008), greater sway velocity (p=.027), and slower performances on the tandem walk (p=.039) and Get Up and Go (p<.001) compared to non-fallers. For the second study, in the same population, we examined 2-year changes in balance self-efficacy (BSE) and the relationship of BSE to side fall risk factors and falls incidence. Results showed BSE at baseline was predictive of Get Up and Go, hip abduction strength and tandem walk at follow-up (p<.008), but that BSE decreased only among the non-fallers (p=.013). In the third study, we examined 3-yr hip bone mineral density (BMD) changes in women with distinct hormone replacement therapy (HRT) profiles: 1) no hormone replacement therapy (N0HRT), 2) HRT continually since menopause (Continual), 3) HRT begun 10 years after menopause (Late), 4) HRT initiated within 5 years (New), and compared the change in BMD of the hip across HRT groups. Only the NoHRT group lost bone over the 3 years (p=.014). We also assessed BMD of the lateral spine across levels of estrogen use in a sub-sample of participants and found long-term HRT users had significantly higher lateral spine BMD (p=.041) compared to women who had never been on HRT. / Graduation date: 2003

This study was designed to investigate the relationship between retinol intake, bone mineral density, and falls in 101 elderly women aged 72 to 90 years (78.6 yrs. �� 4.3 yrs.). Bone mineral density (BMD) (g/cm��) of the left hip, anterior-posterior lumbar spine (L3), and lateral spine (L3) was measured using dual-energy x-ray absorptiometry. Dietary intake and physical activity were assessed by validated questionnaires (the 100-item Block Food Frequency Questionnaire and the Physical Activity Scale for the Elderly, respectively). Isometric hip abduction strength of the right and left legs was assessed using a hand-held dynamometer. Fall surveillance was collected using a "postcard" system at three-month intervals over a two-year period. Multiple regression analyses were used to show the predictability of retinol, vitamin D, calcium, years past menopause, years on hormone replacement therapy, and physical activity on BMD variables. Together, these variables explained 14% of the variance in total hip BMD at follow-up (R��=0.14, SEE=0.12, p=0.020), 26% of the variance in the anterior-posterior spine BMD at follow-up BMD (R��=0.26, SEE=0.17, p=0.051), and 33% of the variance in lateral spine BMD at follow-up (R��=0.33, SEE=0.10, p=0.009). Two-year changes in hip BMD were poorly predicted using the model with only 5% of total hip BMD variance being explained by the six independent variables (R��=0.05, SEE=0.03, p=0.558). Logistic regression was used to determine whether the likelihood of being a faller vs. a non-faller could be predicted from a model using retinol, vitamin D, average hip strength, and physical activity. It was shown that 11.5% of the variability in fall status could be explained by the model (Cox & Snell's R��=0.115). Using an ROC curve analysis, the model correctly classified 69% of the individuals into the correct "fall category". We conclude that retinol, although not an independent predictor of BMD or fall status, is an important component in the prediction of both BMD and falls. Further interventional research is needed to determine the effects of retinol on BMD and falling. / Graduation date: 2004

We evaluated anthropometric and performance measures which best predict bone mineral density (BMD) in 54 adolescent girls (14.6��0.5y; 22.7��14.0 months past menarche). BMD for the whole body, femoral neck, greater trochanter, lumbar spine (L2-L4), and mid-femoral shaft was assessed using dual-energy x-ray absorptiometry (DXA) (Hologic QDR 1000/W). Whole body lean mass and fat mass were derived from the whole body scan. Knee extensor strength and leg power were assessed by isokinetic dynamometry and the Wingate Anaerobic Power Test, respectively. Using simple regression, lean mass was significantly correlated with BMD at all bone sites r=.45-.77; p<0.001), and was more highly correlated with BMD at all sites than was body weight. Maximum leg power was also associated with bone mass at all sites (r=.41-.67; p<0.001) while leg strength correlated significantly with all sites (r=.41-.53; p<0.001) except the lumbar spine. Stepwise regression analyses revealed that 59% of the variance in whole body BMD was predicted by lean mass alone. No other variables, including fat mass, height, months past menarche, leg power, or leg strength, contributed additionally to the regression model. Similarly, lean mass was the only predictor of lumbar spine and femoral shaft BMD (R��=.25, R��=.37, respectively), while femoral neck and trochanteric BMD were best predicted by leg power (R��=.38, R��=.36, respectively). In this group of adolescent girls, lean body mass and leg power independently predicted bone mineral density of the whole body, lumbar spine, femoral shaft, and hip, which may suggest an important role for muscle mass development during growth to maximize peak bone density. / Graduation date: 1997

The purpose of this study was to determine the effects of long-term weighted vest exercise on hip bone mass, functional ability and static balance in elderly women. This was a within subject exercise intervention study and included a 6-month control period. Twenty-three subjects (age 85 �� 6) were recruited and observed for 6-months, then debar a 9-month exercise program. Due to attrition during the control period, five subjects were recruited to add to the exercise group. Training entailed three supervised exercise sessions per week for nine-months designed to overload the lower extremity neuromuscular system. Training stimulus was one of two sets of six to twelve repetitions using weighted vests for progressive resistance. Measurements for bone mineral density (BMD) were assessed using dual energy x-ray absorptiometry (Hologic QDR-1000/W). Static balance measurements were made using the Biodex Stability System. Functional ability tests consisted of: leg strength and power (chair raises and sit to stand) and gait speed (tandem, wide and narrow gait and circular path) and was assessed monthly for six months. Comparisons were conducted using repeated measures analysis of variance. Significant improvements were observed for chair raises 13%, sit to stand 13%, tandem gait 30%, wide gait 22%, narrow gait 20% and circular path 20% following the exercise period. No significant changes were detected (p>0.05) for BMD at the femoral neck and trochanter, but BMD was maintained during the exercise period. Further, there was a trend for improved body composition in the exercise versus the control period. Static balance did not change following the observational or exercise period. In conclusion, a practical exercise program of lower extremity training using weighted vests for resistance improves functional ability in women over 75 years of age. Since improved may function transfer to improved postural stability, these results have important implications for design of exercise programs to reduce fall risk in the elderly. / Graduation date: 1997

The purpose of this study was to compare the levels of bone mineral density (BMD) of the whole body (WB) and proximal femurs of physically active men with spinal cord injuries (SCI) to nonactive men with spinal cord injuries. Also, the lean muscle mass (LMM) of active men with SCI was compared to the LMM of nonactive men with SCI. In addition, BMD values of the radii of physically active men with SCI were compared to that of able bodied men of the same age. The subjects N. 46 were between the age of 20-55 (��=37.83 �� 6.63 years), and were at least 2 years post spinal cord injury. Subjects with SCI were matched on similar level of lesion of the spinal cord, age, height, weight, and years post injury for the purpose of analyzing data. There were 14 active men with paraplegia and 14 nonactive men with paraplegia, 9 active men with quadriplegia and 9 nonactive men with quadriplegia. All BMD data was obtained utilizing a Hologic QDR 1000W dual energy x-ray absorptiometer. A two-factor (level by group) analysis of variance revealed no significant difference for all sites (Whole body, Total hip, radii, LMM) comparing the active and nonactive men with SCI. T-scores and z-scores generated from the Ho logic QDR 1000/W were analyzed using two-factor ANOVA (level by group). The active men with paraplegia had significantly higher BMD levels for all sites when compared to the other groups. These values may be explained by the number of incomplete injuries in the experimental group. Subjects in the physically active group did not clearly show a statistically significant difference on any of the dependent measures. However, values for the dependent measures were higher for the physically active group compared to the values of the nonactive group. / Graduation date: 1995

Introduction and Purpose: Vascular pathologies play an important role in the etiology and progression of number of ocular diseases. Many instruments are developed to monitor retinal hemodynamics, including the Canon Laser Blood Flowmeter (CLBF), in an attempt to better understand the pathophysiology of the disease (Chapter 2). The purpose of this thesis is to determine the impact of light scatter on retinal arteriolar hemodynamic measurement assessed by the CLBF as intraocular light scatter is an inevitable consequence of ageing and particularly cataract. Methodology: Chapter 4 – Artificial light scatter model: One eye from each of 10 healthy young subjects between the ages of 18 and 30 (23.6 ± 3.4) was randomly selected. To simulate light scatter, cells comprising a plastic collar and two plano lenses were filled with solutions of differing concentrations of polystyrene microspheres (Polysciences Inc., USA). 0.002%, 0.004%, 0.006%, 0.008% were prepared, as well as distilled water only. After a preliminary screening to confirm subject eligibility, seven arteriolar hemodynamic measurements were taken by randomly placing the cells between the CLBF objective lens and the subjects’ cornea. Chapter 5 – Ten patients scheduled for extracapsular cataract extraction using phacoemulsification and intraocular lens implantation between the ages of 61 and 84 (mean age 73 years, SD ± 8) were prospectively recruited. Two visits were required to complete the study; One prior to the surgery and one at least six weeks after the surgery to allow for full post-operative recovery. The severity of cataract was documented using the Lens Opacity Classification System (LOCS, III) at the first visit. Each subject underwent visual function assessment at both visits using logMAR Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity charts and the Brightness Acuity Tester (BAT). Retinal arteriolar hemodynamics were measured at both visits using the high intensity setting of the Canon Laser Blood Flowmeter. Results: Chapter 4: Our light scatter model resulted in an artifactual increase of retinal arteriolar diameter (p<0.0001) and thereby increased retinal blood flow (p<0.0001). The 0.006% and 0.008% microsphere concentrations produced significantly higher diameter and flow values than baseline. Centerline blood velocity, however, was not affected by light scatter. Retinal arteriolar diameter values were significantly less with the high intensity laser than with the low intensity laser (p=0.0007). Chapter 5: Group mean retinal arteriolar diameter and blood flow were reduced following extracapsular cataract extraction (Wilcoxon signed-rank test, p=0.022 and p=0.028 respectively); however, centerline blood velocity was unchanged (Wilcoxon signed-rank test, p=0.074). Conclusions: Using an artificial light scatter model (Chapter 3), we demonstrated that the densitometry assessment of vessel diameter is increasingly impacted as the magnitude of artificial light scatter increases; this effect can be partially negated by increasing laser intensity. We showed similar results in the presence of cataract (Chapter 4) by measuring the retinal arteriolar hemodynamics before and after removal of cataract. Care needs to be exercised in the interpretation of studies of retinal vessel diameter that use similar densitometry techniques as cataract is an inevitable consequence of aging.

Introduction and Purpose: Vascular pathologies play an important role in the etiology and progression of number of ocular diseases. Many instruments are developed to monitor retinal hemodynamics, including the Canon Laser Blood Flowmeter (CLBF), in an attempt to better understand the pathophysiology of the disease (Chapter 2). The purpose of this thesis is to determine the impact of light scatter on retinal arteriolar hemodynamic measurement assessed by the CLBF as intraocular light scatter is an inevitable consequence of ageing and particularly cataract. Methodology: Chapter 4 – Artificial light scatter model: One eye from each of 10 healthy young subjects between the ages of 18 and 30 (23.6 ± 3.4) was randomly selected. To simulate light scatter, cells comprising a plastic collar and two plano lenses were filled with solutions of differing concentrations of polystyrene microspheres (Polysciences Inc., USA). 0.002%, 0.004%, 0.006%, 0.008% were prepared, as well as distilled water only. After a preliminary screening to confirm subject eligibility, seven arteriolar hemodynamic measurements were taken by randomly placing the cells between the CLBF objective lens and the subjects’ cornea. Chapter 5 – Ten patients scheduled for extracapsular cataract extraction using phacoemulsification and intraocular lens implantation between the ages of 61 and 84 (mean age 73 years, SD ± 8) were prospectively recruited. Two visits were required to complete the study; One prior to the surgery and one at least six weeks after the surgery to allow for full post-operative recovery. The severity of cataract was documented using the Lens Opacity Classification System (LOCS, III) at the first visit. Each subject underwent visual function assessment at both visits using logMAR Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity charts and the Brightness Acuity Tester (BAT). Retinal arteriolar hemodynamics were measured at both visits using the high intensity setting of the Canon Laser Blood Flowmeter. Results: Chapter 4: Our light scatter model resulted in an artifactual increase of retinal arteriolar diameter (p<0.0001) and thereby increased retinal blood flow (p<0.0001). The 0.006% and 0.008% microsphere concentrations produced significantly higher diameter and flow values than baseline. Centerline blood velocity, however, was not affected by light scatter. Retinal arteriolar diameter values were significantly less with the high intensity laser than with the low intensity laser (p=0.0007). Chapter 5: Group mean retinal arteriolar diameter and blood flow were reduced following extracapsular cataract extraction (Wilcoxon signed-rank test, p=0.022 and p=0.028 respectively); however, centerline blood velocity was unchanged (Wilcoxon signed-rank test, p=0.074). Conclusions: Using an artificial light scatter model (Chapter 3), we demonstrated that the densitometry assessment of vessel diameter is increasingly impacted as the magnitude of artificial light scatter increases; this effect can be partially negated by increasing laser intensity. We showed similar results in the presence of cataract (Chapter 4) by measuring the retinal arteriolar hemodynamics before and after removal of cataract. Care needs to be exercised in the interpretation of studies of retinal vessel diameter that use similar densitometry techniques as cataract is an inevitable consequence of aging.