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.

Bone strength plays an important role in reducing fracture risk. Osteoporosis is a condition as a result of low bone strength and is characterized by deterioration of bone tissue and loss of bone mass, leading to increased fracture risk (Osteoporosis Canada, 2009). Impact loading through exercise has been well established as an activity to maintain and improve bone health (Schwab & Klein, 2008), with high impact activities eliciting a larger response in bone adaptation over low impact activities (Daly, 2007; Guadalupe-Grau, Fuentes, Guerra & Calbet, 2009). The high impact loading of brick breaking within martial arts should be of sufficient magnitude to elicit bone adaptation. PURPOSE: The overall purpose of this study was to examine if the bones of the loaded arm among martial artists with brick breaking experience appear to have adapted to the high impact loading of brick breaking. In order to address this the specific objectives are (1) determine if brick breakers have a larger percent side-to-side difference over age and size matched controls in bone strength index (BSIc) at the 4% radius and 6% ulna, SSIp at the 65% ulna and 50% humerus, and grip strength. (2) Determine if the total number of lifetime brick breaks is correlated with percent side-to-side difference in strength strain index (SSIp), a measure of torsional strength, at the 50% humerus. (3) Confirm the load experienced during the brick break can be considered high impact (>4 X body weight). METHODS: Male brick breakers (N=13, mean age 31.1 (SD 10.5) yrs) and their age and size matched controls (N=13, mean age 31.7 (10.8) yrs) had measurements of SSIp on both arms mid-humeri using pQCT (Stratec XCT2000). Brick breaking history was obtained by questionnaire. SSIp between arms in both groups was assessed by dependant t-tests and percent side-to-side difference (bilateral asymmetry) iii between groups was assessed by independent t-test. Brick breaking force was assessed with 9 black belt participants performing a total of 13 brick break attempts by striking a standard stack of 8 patio blocks on a force platform. RESULTS: Dominant humerus SSIp was 7.7% (124 mm3, p<0.001) greater in brick breakers and 5.3% (96 mm3, p=0.023) greater in controls. Side-to-side differences did not differ between the groups (mean difference of 2.4%, p=0.333). Brick breaking history of total breaks was moderately correlated (r=0.73, p=0.002) with torsional bone strength side-to-side difference. Peak vertical forces ranged from 2075 N to 4496 N (mean: 2960 N). CONCLUSION: Brick breakers bone strength in the loaded arm seemed to have not adapted to high impact forces. However, the association between total number of breaks (impacts) and side-to-side strength difference suggests that a minimum number of loading sessions may be required before significant strength adaptation occurs. The forces experienced during a brick breaking strike approach forces that are considered high impact in lower body activities.

Bone strength plays an important role in reducing fracture risk. Osteoporosis is a condition as a result of low bone strength and is characterized by deterioration of bone tissue and loss of bone mass, leading to increased fracture risk (Osteoporosis Canada, 2009). Impact loading through exercise has been well established as an activity to maintain and improve bone health (Schwab & Klein, 2008), with high impact activities eliciting a larger response in bone adaptation over low impact activities (Daly, 2007; Guadalupe-Grau, Fuentes, Guerra & Calbet, 2009). The high impact loading of brick breaking within martial arts should be of sufficient magnitude to elicit bone adaptation. PURPOSE: The overall purpose of this study was to examine if the bones of the loaded arm among martial artists with brick breaking experience appear to have adapted to the high impact loading of brick breaking. In order to address this the specific objectives are (1) determine if brick breakers have a larger percent side-to-side difference over age and size matched controls in bone strength index (BSIc) at the 4% radius and 6% ulna, SSIp at the 65% ulna and 50% humerus, and grip strength. (2) Determine if the total number of lifetime brick breaks is correlated with percent side-to-side difference in strength strain index (SSIp), a measure of torsional strength, at the 50% humerus. (3) Confirm the load experienced during the brick break can be considered high impact (>4 X body weight). METHODS: Male brick breakers (N=13, mean age 31.1 (SD 10.5) yrs) and their age and size matched controls (N=13, mean age 31.7 (10.8) yrs) had measurements of SSIp on both arms mid-humeri using pQCT (Stratec XCT2000). Brick breaking history was obtained by questionnaire. SSIp between arms in both groups was assessed by dependant t-tests and percent side-to-side difference (bilateral asymmetry) iii between groups was assessed by independent t-test. Brick breaking force was assessed with 9 black belt participants performing a total of 13 brick break attempts by striking a standard stack of 8 patio blocks on a force platform. RESULTS: Dominant humerus SSIp was 7.7% (124 mm3, p<0.001) greater in brick breakers and 5.3% (96 mm3, p=0.023) greater in controls. Side-to-side differences did not differ between the groups (mean difference of 2.4%, p=0.333). Brick breaking history of total breaks was moderately correlated (r=0.73, p=0.002) with torsional bone strength side-to-side difference. Peak vertical forces ranged from 2075 N to 4496 N (mean: 2960 N). CONCLUSION: Brick breakers bone strength in the loaded arm seemed to have not adapted to high impact forces. However, the association between total number of breaks (impacts) and side-to-side strength difference suggests that a minimum number of loading sessions may be required before significant strength adaptation occurs. The forces experienced during a brick breaking strike approach forces that are considered high impact in lower body activities.

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.

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. / Medicine, Faculty of / Medicine, Department of / Experimental Medicine, Division of / Graduate

Bone quality and the conditions that affect it make up a large field of study. One specific area of interest is the loss in bone strength during exposure to microgravity. The femoral neck (FN) region in particular is an important region of study since a FN failure has such a detrimental effect on mobility. The objective of this study was to characterize the effects of microgravity and recovery on the FN in the adult male hindlimb unloaded (HU) rat model. This was done through peripheral quantitative computed tomography (pQCT), mechanical testing in two different loading conditions, and estimated strength indices. Adult male Sprague-Dawley rats (6-mo) were grouped into baseline (BL), ambulatory cage control (CC) and hindlimb unloaded (HU); HU and CC animals were further divided into sub-groups (n=15 each): HU euthanized after 28 days of suspension, and HU euthanized after 28, 56, and 84 days of recovery with CC groups being euthanized at each of these time points. The excised right and left femoral necks were both scanned ex vivo using pQCT. Quasi-static mechanical testing was performed with the right femurs positioned vertically and the left femurs positioned laterally at a -10 degree angle. A series of strength indices was used to attempt to predict the mechanical testing results, including a compression index, a bending index and an alternative combination of the two. HU exposure led to 6.3 percent lower bone mineral content (BMC), compared to BL and 7.8 percent lower total volumetric bone mineral density (vBMD) at the FN. The vertical or axial loading showed a 17.1 percent drop in mechanical strength due to HU exposure. The lateral loading test revealed a 5.4 percent drop in strength, showing that HU had a greater effect on the axial loading configuration. Also, after just 28 days of recovery, the axial loading test revealed a complete recovery of strength. None of the strength indexes completely predicted the mechanical behavior of the FN. In the right femur, the combined index had the highest correlation with an R value of 0.94. The bending strength index had the highest correlation in the left lateral testing with an R value of 0.98. However, in all the cases, the strength indexes failed to predict the mechanical behavior at all the time points. In general, the strength indexes provide valuable input, but fail to replace mechanical testing.

Bone loss is an important skeletal indicator of environmental stress. Cortical and trabecular bone, however, are differentially affected by various stressors. Peripheral quantitative computed tomography (pQCT) potentially addresses this issue by separately calculating cortical and trabecular bone mineral density (BMD). This project had two major goals: evaluate the effectiveness of pQCT in measuring BMD in archaeological specimens, and test the hypothesis that females suffered greater bone loss than males in a socially stressed population. Cortical and trabecular BMD was measured in the radius and femur of skeletons from Point of Pines Pueblo, Arizona. pQCT effectively measured BMD in the sample, but the hypothesis that females suffered greater BMD loss than males was not supported. Females showed no significant BMD loss in the radius, while males experienced no significant changes in cortical density. Sex-specific activities may explain bone maintenance in the female radius, while hormonal differences likely maintained male cortical density.

Introduction: Puberty is a crucial period for rapid changes in bone mineral, size, geometry, and microarchitecture. The mechanostat theory postulates that increased mechanical loading will affect bone phenotype and strength during development and in later life. Individuals with cystic fibrosis (CF) have an increased risk of developing osteoporosis and fragility fractures in young adulthood, which may be caused by poor growth. The aim was to investigate whether sex and disease status modified the relationship between: 1) puberty and bone, and 2) muscle and bone. This would contribute to the understanding of how sex (males vs. females) and disease group (CF vs.controls) alters the relationship between bone and muscle in children and adolescents as they transition through puberty and who, on a population level, differ in the prevalence of osteoporosis and risk of fracture in later life. Methods and Analyses: This observational study used novel imaging and muscle assessment techniques to measure bone and muscle parameters in White Caucasian children and adolescents, aged 8 to 16 years, living in the UK, with children with CF (n=65) and controls (n=151). Anthropometry and pubertal status were assessed. Dual energy X-ray absorptiometry, peripheral quantitative computed tomography (pQCT), high-resolution pQCT, and jumping mechanography were used to measure bone and muscle outcomes. ANCOVA with Scheffé post hoc and multiple linear regression tests were performed. Data were adjusted according to the research aims and included covariates; sex, disease group, pubertal stage, age, quadratic age, height, weight, maximum force (Fmax), and maximum power (Pmax). Data are presented as beta-coefficient (%) and p-value, with the significance level set to p < 0.05. Results: In height adjusted analyses, among healthy participants, females had smaller bones and lower bone density compared to males. With pubertal maturation, females had lower apparent gains in the distal and proximal total area (Tt.Ar and CSA), distal cortical porosity (Ct.Po) and proximal bone strength (SSI) but higher apparent gains in distal and proximal cortical bone density(Ct.BMD, Ct.TMD, vBMD). Females had consistently lower distal total area (total CSA) and density (total vBMD), distal trabecular density(BV/TV) and number(Tb.N), and proximal cortical area(CSA) compared to males, across all stages of puberty. With increasing muscle force (Fmax), females had higher apparent gains in total body less head bone mineral (TBLH BMC) and bone area(BA), distal total and trabecular density (total and trab vBMD) compared to males. In contrast, with increasing muscle power (Pmax), females had higher apparent gains in distal total and cortical densities (D100, Ct.BMD and Ct.TMD), and distal trabecular thickness (Tb.Th), and proximal cortical density (cortical vBMD) but lower apparent gains in distal cortical porosity (Ct.Po) and trabecular number (Tb.N) compared to males. In height adjusted analyses, participants with CF had smaller bones and lower bone density compared to controls. With increasing pubertal maturation, participants with CF had lower apparent gains in total body less head bone mineral and bone area, and in distal trabecular density, cortical porosity, and trabecular thickness compared to controls. Participants with CF had consistently lower distal total and cortical area, distal total and trabecular densities and proximal bone strength compared to controls, across all stages of puberty. With increasing muscle force, participants with CF had lower apparent gains in total body less head bone mineral and bone area, distal total density, trabecular density, and trabecular number. In contrast, with increasing muscle power (Pmax), participants with CF had higher apparent gains in distal trabecular density (BV/TV) and trabecular number (Tb.N) compared to controls. Conclusion: These findings suggests that sex and disease status do modify the relationships between puberty and bone, and between muscle function and bone. Skeletal adaptation to muscle differs between sexes and in populations with chronic disease, which may explain sex and disease group differences in risks of osteoporosis and fracture. Bone adaptation to muscle in children with CF is altered, which may lead to narrow, under-mineralised bones, with lower bone strength in later life. Understanding better impairments in muscle functions may provide targets for intervention to improve skeletal health in later life.

Die Osteoporose ist als häufigste Knochenerkrankung im Alter die Ursache vieler Beeinträchtigungen. Definiert wird sie über die Knochendichte, die unter anderem mit der peripheren quantitativen Computertomographie (pQCT) bestimmt werden kann. Mit unseren Daten aus Knochendichtemessungen per pQCT am distalen Radius (XCT 2000) und an der distalen Tibia (XCT 3000) konnten wir im Tukey-HSD-Test zeigen, dass die Knochendichteparameter an oberer und unterer Extremität gut miteinander korrelieren. Es wurden die trabekuläre und die totale Dichte sowie der polare stress-and-strain-Index berücksichtigt. Die trabekuläre Knochendichte an der Tibia, dem gewichtstragenden Knochen, ist höher als die am Radius. Einflussnahme auf die Knochendichte konnte mittels Regressionsanalyse für das Alter, das Geschlecht, die Größe, das Gewicht und den BMI nachgewiesen werden. Die altersbedingte Abnahme der Knochendichte ist an der Tibia stärker ausgeprägt als am Radius. Bei der Frau bedingt eine hohe totale Dichte am Radius eine höhere Festigkeit an der Tibia als bei entsprechenden Dichtewerten beim Mann. Unter Mitberücksichtigung des Alters steigt die Festigkeit an der Tibia beim Mann mit den Jahren an. Bei der Frau sinkt sie, wie auch am Radius, mit steigendem Alter. Das Gewicht nimmt signifikanten Einfluss auf die untere Extremität, nicht jedoch auf den Radius. Die Betrachtung des BMI zeigt, dass nicht die reine Gewichtszunahme sondern die Kombination aus Größe und Gewicht diesen positiven Effekt erzielen, Fettleibigkeit ab dem Adipositasgrad aber einen negativen Einfluss auf die Knochendichte und -festigkeit hat. / As a common bone disease in elderly patients osteoporosis is a cause of severe physical impairment. It is defined by bone mineral density (BMD), which can be determined by peripheral quantitative computer tomography (pQCT). Our data from BMD measurements made by pQCT at the distal radius (XCT 2000) and at the distal tibia (XCT 3000) shows through application of the Tukey-HSD-tests that BMD values at the upper and lower extremities correlate with each other. Total and trabecular BMD as well as the polar stress-and-strain index are considered. Trabecular BMD at the body weight bearing distal tibia is higher than at the distal radius. Influence on BMD was verified by regression analysis for age, sex, height, weight and BMI. Age-related decrease of BMD is more distinct at the tibia than at the radius. In women high total BMD accounts for higher strength at the tibia than it does for corresponding values in men. Considering age, strength of the tibia increases in men during the years. In women it decreases, like it does at the radius. Weight has significant influence on the lower extremity, however not on the radius. Regarding the BMI, not just an increase in mass but a combination of weight and height causes this positive effect. Obesity above level I has a negative influence on BMD and bone strength.

These PhD projects represent secondary analyses of data from the ongoing Iowa Fluoride Study (IFS)/Iowa Bone Development Study (IBDS). The aim of this dissertation was to explore the associations between period-specific and cumulative fluoride intakes from birth to age 17, and from birth to age 19 years and bone measures of participants. Also, this dissertation looked into the associations between the clinical presence of dental fluorosis and bone outcomes. Participants have been participating in the IBDS that grew out of the IFS, which is a longitudinal investigation of dietary and non-dietary fluoride exposures, dental fluorosis and dental caries. IFS participants were recruited during 1992-95 from 8 hospital postpartum wards in Iowa, and detailed questionnaires were sent every 1.5-6 months. Data on intakes from water, other beverages, selected foods, dietary fluoride supplements and dentifrice were collected from the questionnaires, and, in combination with water and beverage fluoride levels, combined fluoride was estimated. For the first dissertation project, the association between fluoride intake and peripheral quantitative computed tomography (pQCT)-derived bone outcomes at age 17 were assessed. Participants underwent pQCT of the radius and tibia (XCT-2000) at age 17 years. pQCT results of trabecular bone mineral density (BMD) and bone mineral content (BMC), cortical BMD and BMC, and compression and torsion strength were related to fluoride intake through bivariate and multivariable analyses, adjusting for height, weight, years since peak height velocity, average daily time spent in moderate-to-vigorous intensity physical activity, daily calcium intake, and daily protein intake. P-values < 0.01 were considered statistically significant rather than p< 0.05 due to multiple hypothesis tests. The mean daily fluoride intake estimated by area-under-the-curve (AUC) from birth to 17 years was 0.79 mg (SD = 0.32) for males and 0.70 mg (SD = 0.25) for females. Spearman correlation coefficients between daily fluoride intake and pQCT bone measures were weak (for females r= -0.01 to 0.15 for radius bone outcomes and -0.001 to 0.23 for tibia bone outcomes; for males r= 0.03 to 0.24 for radius bone outcomes and -0.008 to 0.27 for tibia bone outcomes). In sex-specific linear regression analyses for females, partially-adjusted for height, weight, and years since peak height velocity, statistically significant negative associations were detected between all radial bone outcomes and period-specific fluoride intake from 0-8.5 years. Significant positive associations were detected for females between period-specific fluoride intakes from 14-17 years and all tibia bone outcomes, and between period-specific fluoride intakes from 14-17 years and all radius and tibia bone outcomes for males. In the fully-adjusted models, which also included physical activity, protein intake and calcium intake, statistically suggestive negative associations were detected for females during the early fluoride intake period from 0 to 8.5 years and radial cortical bone content and torsion bone strength. A statistically suggestive positive association was found between period-specific fluoride intake from 8.5 to 14 years and torsion bone strength (pSSI) (p< 0.05) for females. For males, statistically significant positive associations were detected between fluoride intake for the period from 14 to 17 years and cortical content and torsion strength (pSSI) at the 0.01 level. The second project examined the associations between period-specific and cumulative fluoride intakes from birth to age 19 years and MDCT-derived bone outcomes at age 19. Age 19 MDCT-derived trabecular and cortical bone micro-architecture scans were acquired at the University of Iowa Comprehensive Lung Imaging Center. MDCT results of the trabecular (volumetric bone mineral density (vBMD), transpose bone mineral density (tBMD), plate trabecula bone mineral density (pBMD), plate width (TS-PW), trabecular thickness (Tb.Th), trabecular spacing (Tb.Sp), trabecular network area (Tb.NA)) and cortical (cortical bone porosity (Cb.Poro), cortical thickness (Cb.Th)) bone were related to fluoride intake through bivariate and multivariable analyses, adjusting for height, weight, years since peak height velocity, average daily time spent in moderate-to-vigorous intensity physical activity, Healthy Eating Index (HEI) score, calcium intake and protein intake. P-values < 0.01 were considered statistically significant rather than p< 0.05 due to multiple hypothesis tests. The mean daily fluoride intake estimated by area-under-the-curve (AUC) from birth to 19 years was 0.81 mg (SD = 0.33) for males and 0.69 mg (SD = 0.27) for females. Spearman correlation coefficients between daily fluoride intake and MDCT bone measures were weak (for females r= -0.001 to 0.20 for trabecular bone outcomes and -0.01 to 0.02 for cortical bone outcomes; for males r= -0.003 to 0.16 for trabecular bone outcomes and -0.09 to -0.02 for cortical bone outcomes). In sex-specific partially-adjusted regression analysis adjusted for height, weight, and years since peak height velocity, no statistically significant associations were found for females or males. In the fully-adjusted models, which also included physical activity, HEI score, and protein and calcium intakes, no statistically significant associations were found for either females or males. The third project explored the associations between dental fluorosis score at age 8 and DXA-derived bone outcomes at age 5. DXA bone assessments of the whole body, proximal femur (hip), and lumbar spine were performed at The University of Iowa in the Clinical Research Center (Hologic QDR-2000 DXA unit). The dental fluorosis score was defined as the proportion of zones with definitive or severe fluorosis per person. In the unadjusted associations between bone outcomes and dental fluorosis score, no statistically significant associations were detected for females at the 0.05 level. For males, a statistically significant negative association was found between hip BMD and dental fluorosis score. Sex-specific partial correlation coefficients were estimated between DXA-derived bone outcomes and dental fluorosis score adjusted for height, weight, physical activity, calcium intake and fluoride intake. No statistically significant associations were found for females. For males, a statistically significant negative association was detected between dental fluorosis score and hip BMD. The findings of this dissertation show that life-long intakes from combined sources for adolescents and young adults living in fluoridated areas in the United States were weakly associated with bone measures at age 17 and 19. Furthermore, it was shown that bone outcomes can’t be predicted by the score of dental fluorosis. Fluoride is a mineral that plays an important role in the mineralization of bone and teeth, as well as in dental caries prevention. Numerous professional health organizations endorse the adjusted fluoridation of public water supplies for caries prevention. Results from this dissertation will also help in supporting additional efforts to promote water fluoridation and expand its use, as this dissertation’s outcomes did not demonstrate adverse outcomes related to bone.