Deep learning-based harmonization of trabecular bone microstructures between high- and low-resolution CT imaging.

BACKGROUND: Osteoporosis is a bone disease related to increased bone loss and fracture-risk. The variability in bone strength is partially explained by bone mineral density (BMD), and the remainder is contributed by bone microstructure. Recently, clinical CT has emerged as a viable option for in vivo bone microstructural imaging. Wide variations in spatial-resolution and other imaging features among different CT scanners add inconsistency to derived bone microstructural metrics, urging the need for harmonization of image data from different scanners. PURPOSE: This paper presents a new deep learning (DL) method for the harmonization of bone microstructural images derived from low- and high-resolution CT scanners and evaluates the method's performance at the levels of image data as well as derived microstructural metrics. METHODS: We generalized a three-dimensional (3D) version of GAN-CIRCLE that applies two generative adversarial networks (GANs) constrained by the identical, residual, and cycle learning ensemble (CIRCLE). Two GAN modules simultaneously learn to map low-resolution CT (LRCT) to high-resolution CT (HRCT) and vice versa. Twenty volunteers were recruited. LRCT and HRCT scans of the distal tibia of their left legs were acquired. Five-hundred pairs of LRCT and HRCT image blocks of 64 × 64 × 64 $64 \times 64 \times 64 $ voxels were sampled for each of the twelve volunteers and used for training in supervised as well as unsupervised setups. LRCT and HRCT images of the remaining eight volunteers were used for evaluation. LRCT blocks were sampled at 32 voxel intervals in each coordinate direction and predicted HRCT blocks were stitched to generate a predicted HRCT image. RESULTS: Mean ± standard deviation of structural similarity (SSIM) values between predicted and true HRCT using both 3DGAN-CIRCLE-based supervised (0.84 ± 0.03) and unsupervised (0.83 ± 0.04) methods were significantly (p < 0.001) higher than the mean SSIM value between LRCT and true HRCT (0.75 ± 0.03). All Tb measures derived from predicted HRCT by the supervised 3DGAN-CIRCLE showed higher agreement (CCC  ∈ $ \in $ [0.956 0.991]) with the reference values from true HRCT as compared to LRCT-derived values (CCC  ∈ $ \in $ [0.732 0.989]). For all Tb measures, except Tb plate-width (CCC = 0.866), the unsupervised 3DGAN-CIRCLE showed high agreement (CCC  ∈ $ \in $ [0.920 0.964]) with the true HRCT-derived reference measures. Moreover, Bland-Altman plots showed that supervised 3DGAN-CIRCLE predicted HRCT reduces bias and variability in residual values of different Tb measures as compared to LRCT and unsupervised 3DGAN-CIRCLE predicted HRCT. The supervised 3DGAN-CIRCLE method produced significantly improved performance (p < 0.001) for all Tb measures as compared to the two DL-based supervised methods available in the literature. CONCLUSIONS: 3DGAN-CIRCLE, trained in either unsupervised or supervised fashion, generates HRCT images with high structural similarity to the reference true HRCT images. The supervised 3DGAN-CIRCLE improves agreements of computed Tb microstructural measures with their reference values and outperforms the unsupervised 3DGAN-CIRCLE. 3DGAN-CIRCLE offers a viable DL solution to retrospectively improve image resolution, which may aid in data harmonization in multi-site longitudinal studies where scanner mismatch is unavoidable.

Generalized permanent dentition fluorosis severity becomes less evident over time among a birth cohort.

Objectives: There are relatively few cohort studies which have examined changes in fluorosis appearance over time, and none of these have assessed changes in generalized fluorosis. In this analysis, we quantified and assessed changes in multiple measures of generalized fluorosis severity through childhood, adolescence, and young adulthood. Methods: Participants were from the Iowa Fluoride Study, a birth cohort recruited from 1992 to 1995. Permanent dentition fluorosis exams were carried out at ages 9, 13, 17, and 23 years using the Fluorosis Risk Index (FRI). Generalized fluorosis was assessed using mean FRI scores at the tooth- and person-level as well as a five-category measure of generalized fluorosis. Generalized fluorosis prevalence and severity was summarized at each time point and differences in adjacent time points were assessed using gamma statistics, signed-rank tests, and plotting changes in generalized fluorosis between adjacent time points. Results: We observed a statistically significant decline in the percentage of non-zero mean FRI scores at later exam ages at both the person- and tooth-levels. Based on our five-category generalized fluorosis measure, there were 34.0%-54.1% of participants with generalized fluorosis at baseline for each tooth group, and these percentages declined to 8.9%-27.2% at the age 23-year exam. Conclusions: We observed a statistically significant decline in generalized fluorosis severity scores and overall prevalence at later exam ages across all three measures of generalized fluorosis severity. This trend should be accounted for when estimating the prevalence of fluorosis in a population using fluorosis severity data collected in children and adolescents.

Continuum finite element analysis generalizesin vivotrabecular bone microstructural strength measures between two CT scanners with different image resolution.

Fragility of trabecular bone (Tb) microstructure is increased in osteoporosis, which is associated with rapid bone loss and enhanced fracture-risk. Accurate assessment of Tb strength usingin vivoimaging available in clinical settings will be significant for management of osteoporosis and understanding its pathogenesis. Emerging CT technology, featured with high image resolution, fast scan-speed, and wide clinical access, is a promising alternative forin vivoTb imaging. However, variation in image resolution among different CT scanners pose a major hurdle in CT-based bone studies. This paper presents nonlinear continuum finite element (FE) methods for computation of Tb strength fromin vivoCT imaging and evaluates their generalizability between two scanners with different image resolution. Continuum FE-based measures of Tb strength under different loading conditions were found to be highly reproducible (ICC ≥ 0.93) using ankle images of twenty healthy volunteers acquired on low- and high-resolution CT scanners 44.6 ± 2.7 days apart. FE stress propagation was mostly confined to Tb micro-network (2.3 ± 1.7 MPa) with nominal leakages over the marrow space (0.4 ± 0.5 MPa) complying with the fundamental principle of mechanics atin vivoimaging. In summary, nonlinear continuum FE-based Tb strength measures are reproducible among different CT scanners and suitable for multi-site longitudinal human studies.

Patterns of fluoride intake from 6 to 17 years of age: The Iowa Fluoride Study.

OBJECTIVES: This article reports on estimated daily fluoride intake from water, other beverages and selected foods, dentifrice, and dietary fluoride supplements by both individual sources, and all sources combined, among 787 children participating in the Iowa Fluoride Study (IFS) from 6 to 17 years of age. METHODS: Total daily fluoride intake (mg F) and fluoride intake per kilogram bodyweight (mg F/kg bw) were estimated using responses to questionnaires sent every 3-6 months. Dietary assessments included frequencies and amounts of beverage intake for the previous week from water, milk, ready-to-drink beverages, beverages made by adding water to concentrate or powder, and selected foods with substantial water content. Descriptive statistics and bivariate and multivariable analyses with linear mixed models were used to assess associations with each of mg F and mg F/kg bw. RESULTS: Mean combined dietary fluoride (mg F) from all sources examined in the study increased slightly with age, whereas the fluoride intake per kg bw decreased with age. Age, sex, and socioeconomic status were significantly associated with fluoride intake (mg F and mg F/kg bw). Each year increase in age was associated with a 0.02-mg increase in fluoride consumption, on average, after adjusting for the effects of covariates. CONCLUSIONS: Daily mean fluoride intakes from single and combined sources were relatively stable, while the intake of fluoride per kg bw decreased from 6 to 17 years of age. Fluoridated water was the major source of ingested fluoride, contributing over 50% of total daily intake at all ages.

Fluoride Content of Ready-to-Eat Infant Foods and Drinks in Australia.

The use of fluoride is effective in preventing dental caries. However, an excessive intake of fluoride leads to dental fluorosis, making it necessary to regularly monitor the fluoride intake especially for infants. There is hitherto a lack of information on fluoride content in infant foods from an Australian perspective. Therefore, this study aims to estimate the amount of fluoride content from a range of commercially available ready-to-eat (RTE) infant foods and drinks available in Australia. Based on an external calibration method, potentiometry involving a fluoride ion selective electrode and a silver|silver chloride reference electrode was conducted to analyse the fluoride content of a total of 326 solid food samples and 49 liquid food samples in this work. Our results showed an overall median (range) fluoride content of 0.16 (0.001-2.8) µg F/g of solid food samples, and 0.020 (0.002-1.2) µg F/mL of liquid food samples. In addition, ~77.5% of the liquid samples revealed a fluoride content < 0.05% µg F/mL. The highest variation of fluoride concentration (0.014-0.92 µg F/g) was found in formulas for ≥6 month-old infants. We have attributed the wide fluoride content variations in ready-to-eat infant foods and drinks to the processing steps, different ingredients and their origins, including water. In general, we found the fluoride content in most of the collected samples from Australian markets to be high and may therefore carry a risk of dental fluorosis. These results highlight the need for parents to receive appropriate information on the fluoride content of ready-to-eat infant food and drinks.

Prevalence of non-cavitated lesions and progression, regression, and no change from age 9 to 23 years.

OBJECTIVES: Some non-cavitated caries lesions (D1 ), the initial stage of caries, progress to cavitation. This article reports participant-level and surface-level D1 prevalence and changes in status of D1 lesions through different periods from age 9 to 23. METHODS: The Iowa Fluoride Study (IFS) participants were followed longitudinally; all permanent tooth surfaces were examined clinically for caries at ages 9, 13, 17, and 23 using standardized criteria for sound (S), questionable (D0 ), non-cavitated (D1 ), cavitated (D2+ ), filled (F), or missing due to decay (M). D1 lesions at the beginning of each interval were reassessed at each follow-up age to determine transitions (to the 5 categories or no transition). RESULTS: The sample had relatively high socioeconomic status (SES), with about 52%-55% high SES, 32-35% middle SES, and 12-13% low SES. Person-level prevalences of D1 lesions were 23%, 38%, 60%, and 45% at ages 9, 13, 17, and 23, respectively. Surface-level prevalences were less than 1% at ages 9 and 13, 3% at 17, and 2% at 23. Thirteen percent of D1 s at age 9 progressed at 13, 18% progressed from 13 to 17, and 11% progressed from 17 to 23. The percentages regressing (to sound or D0 ) were 72%, 54%, and 72%, respectively. CONCLUSION: Non-cavitated lesions were more prevalent at age 17 than at ages 9, 13, and 23. The high rates of regression compared to progression or no change suggest that many non-cavitated lesions do not progress to cavitated lesions and could be reversed; therefore, surgical intervention should not be the treatment of choice for incipient lesions.

Computed Tomography-Based Stiffness Measures of Trabecular Bone Microstructure: Cadaveric Validation and In Vivo Application.

Osteoporosis causes bone fragility and elevates fracture risk. Applications of finite element (FE) analysis (FEA) for assessment of trabecular bone (Tb) microstructural strength at whole-body computed tomography (CT) imaging are limited due to challenges with Tb microstructural segmentation. We present a nonlinear FEA method for distal tibia CT scans evading binary segmentation of Tb microstructure, while accounting for bone microstructural distribution. First, the tibial axis in a CT scan was aligned with the FE loading axis. FE cubic mesh elements were modeled using image voxels, and CT intensity values were calibrated to ash density defining mechanical properties at individual elements. For FEA of an upright volume of interest (VOI), the bottom surface was fixed, and a constant displacement was applied at each vertex on the top surface simulating different loading conditions. The method was implemented and optimized using the ANSYS software. CT-derived computational modulus values were repeat scan reproducible (intraclass correlation coefficient [ICC] ≥ 0.97) and highly correlated (r ≥ 0.86) with the micro-CT (µCT)-derived values. FEA-derived von Mises stresses over the segmented Tb microregion were significantly higher (p < 1 × 10-11) than that over the marrow space. In vivo results showed that both shear and compressive modulus for males were higher (p < 0.01) than for females. Effect sizes for different modulus measures between males and females were moderate-to-high (≥0.55) and reduced to small-to-negligible (<0.40) when adjusted for pure lean mass. Among body size and composition attributes, pure lean mass and height showed highest (r ∈ [0.45 0.56]) and lowest (r ∈ [0.25 0.39]) linear correlation, respectively, with FE-derived modulus measures. In summary, CT-based nonlinear FEA provides an effective surrogate measure of Tb microstructural stiffness, and the relaxation of binary segmentation will extend the scope for FEA in human studies using in vivo imaging at relatively low-resolution. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Primary Caregiver Retention and Perceptions of Retention Strategies in a 36-Month Prospective Childhood Caries Study.

INTRODUCTION/OBJECTIVES: This paper reports on participant retention from an ongoing prospective, multi-site cohort caries risk study involving parent/infant pairs. The objectives were to: (1) compare the retention rates at each intermediate contact (every 4 months) and dental visit (every 18 months) across the 3 clinical sites, (2) assess primary caregivers' perceptions at the end of the study about the retention efforts used in this longitudinal study, and (3) determine whether primary caregiver baseline demographic characteristics and child's baseline caries experience were associated with retention. METHODS: 1325 primary caregiver-child pairs recruited at the child's first birthday were followed for 36 months at 3 sites. Dental visits occurred at children's ages of approximately 12, 30, and 48 months. Telephone/email intermediate contacts with the primary caregiver occurred 6 times between dental visits. The outcome variable was the retention rates at each dental visit and each intermediate contact. Primary caregivers' perceptions of intermediate contacts were evaluated. Retention rates were compared by maternal age, race, ethnicity, Medicaid status, yearly household income, baseline caries experience (defined as decayed, missing due to caries, or filled tooth surfaces) at 12 months, and the number of teeth erupted. RESULTS: 1325 primary caregiver/infant pairs were enrolled and completed the first in-person dental visit, 1062 pairs (80%) completed the second visit and 985 (74%) completed the third. Most primary caregivers were female (94%), with a mean age of 29 years and 667 (50%) self-identified as White, 544 (41%) as Black, and 146 (11%) as Hispanic. The percentages of successful intermediate contacts were 95% at 4 months decreasing to 82% at 34 months. Almost all 964 (98%) of 985 primary caregivers reported at the last visit that they were comfortable/very comfortable with 4-month intermediate contacts. The multivariable analysis showed that primary caregivers who were older (OR = 1.07; 95% CI, 1.04-1.09) and White (OR = 1.52; 95% CI, 1.12-2.06) were more likely to complete the study. CONCLUSIONS: Retention strategies were focused on frequent routine contact and increasing monetary incentives. Those strategies may have resulted in retention exceeding the proposed goals. At the end of the study, primary caregivers were comfortable with the 4-month intermediate contacts.

Associations between body mass index and body composition measures in a birth cohort.

BACKGROUND: Associations among body composition measures have been limited to cross-sectional analyses of different subjects. We identified cross-sectional relationships between body mass index (BMI) and other body composition measures and predicted body composition measures from BMI throughout childhood and adolescence. METHODS: BMI was calculated and % body fat (%BF), fat mass index (FMI), and fat-free mass index (FFMI) were measured using dual-energy x-ray absorptiometry at ages 5, 9, 11, 13, 15, and 17 years in a birth cohort (n = 629). Sex-specific body composition measures were calculated for BMI-for-age percentiles; associations between BMI and body composition measures were characterized; and body composition measures were predicted from BMI. RESULTS: %BF, FMI, and FFMI generally increased with BMI-for-age percentiles at each age. Correlations between BMI and %BF or FMI were generally higher at BMI-for-age percentiles ≥95% than for lower BMI-for-age percentiles. Correlations between BMI and FFMI were generally higher for participants at very low and very high BMI-for-age percentiles than at moderate BMI-for-age percentiles. Age- and sex-specific predictions from BMI are provided for %BF, FM, and FFMI. CONCLUSIONS: Sex-specific body composition measures throughout childhood and adolescence are presented. BMI is a better indicator of adiposity at higher than at lower BMI values. IMPACT: Sex-specific body composition measures throughout childhood and adolescence are described. % BF, FMI, and FFMI generally increased with BMI-for-age percentiles for both sexes throughout childhood and adolescence. BMI is a better indicator of adiposity at higher BMI levels than at lower BMI values throughout childhood and adolescence.

Association of Early Childhood Caries with Bitter Taste Receptors: A Meta-Analysis of Genome-Wide Association Studies and Transcriptome-Wide Association Study.

Although genetics affects early childhood caries (ECC) risk, few studies have focused on finding its specific genetic determinants. Here, we performed genome-wide association studies (GWAS) in five cohorts of children (aged up to 5 years, total N = 2974, cohorts: Center for Oral Health Research in Appalachia cohorts one and two [COHRA1, COHRA2], Iowa Fluoride Study, Iowa Head Start, Avon Longitudinal Study of Parents and Children [ALSPAC]) aiming to identify genes with potential roles in ECC biology. We meta-analyzed the GWASs testing ~3.9 million genetic variants and found suggestive evidence for association at genetic regions previously associated with caries in primary and permanent dentition, including the ß-defensin anti-microbial proteins. We then integrated the meta-analysis results with gene expression data in a transcriptome-wide association study (TWAS). This approach identified four genes whose genetically predicted expression was associated with ECC (p-values < 3.09 × 10−6; CDH17, TAS2R43, SMIM10L1, TAS2R14). Some of the strongest associations were with genes encoding members of the bitter taste receptor family (TAS2R); other members of this family have previously been associated with caries. Of note, we identified the receptor encoded by TAS2R14, which stimulates innate immunity and anti-microbial defense in response to molecules released by the cariogenic bacteria, Streptococcus mutans and Staphylococcus aureus. These findings provide insight into ECC genetic architecture, underscore the importance of host-microbial interaction in caries risk, and identify novel risk genes.

Activity Level and Sport Type in Adolescents Correlate with the Development of Cam Morphology.

BACKGROUND: The purpose of this study was to evaluate the influence of the volume and type of sport on the development of cam-type femoroacetabular impingement and acetabular dysplasia. METHODS: The Physical Activity Questionnaire for Adolescents (PAQ-A) was administered to Iowa Bone Development Study participants at the age of 17 years to identify those who had participated in at least 2 seasons of high school interscholastic sports. Based on relative peak strain and ground reaction forces, subjects were grouped as power sport athletes (basketball, cheerleading, football, gymnastics, soccer, and volleyball), non-power sport athletes (wrestling, baseball, cross-country or track and field, softball, or tennis), or non-athletes. Using anteroposterior views of the left hip formatted from dual x-ray absorptiometry (DXA) scans, the alpha angle, head-neck offset ratio (HNOR), and lateral center-edge angle (LCEA) were evaluated longitudinally at the ages of 17, 19, and 23 years. Logistic regression was used to evaluate the odds of hip cam morphology (alpha angle >55° and/or HNOR <0.17) or acetabular dysplasia (LCEA <24°) at the age of 23 years in all athlete groups. The relationships between physical activity level and hip measures (alpha angle, HNOR, and LCEA) from the ages of 17 to 23 years were examined using linear mixed models adjusted for sex. RESULTS: Compared with non-athletes at the age of 23 years, power sport athletes had significantly greater odds of cam morphology according to the alpha angle (odds ratio [OR], 2.93 [95% confidence interval (CI), 1.02 to 8.41]; p = 0.046) and HNOR (OR, 1.91 [95% CI, 1.01 to 3.60]; p = 0.047), but not greater odds of acetabular dysplasia (p > 0.05). There were no significant differences in the odds of cam morphology or acetabular dysplasia in non-power sport athletes compared with non-athletes (all p > 0.05). Higher physical activity levels were significantly associated with an increase in the alpha angle (beta and standard error, 0.77° ± 0.30°; p = 0.011) and a decrease in the HNOR (-0.003 ± 0.001; p = 0.003), but not the LCEA (-0.05 ± 0.15; p = 0.744). CONCLUSIONS: A higher volume of physical activity and participation in sports with higher peak strain and ground reaction forces during the process of skeletal maturation may increase the risk of developing cam morphology during late adolescence. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Tooth Eruption and Early Childhood Caries: A Multisite Longitudinal Study.

Purpose: The purpose of this study was to assess the relationship between the number of teeth present at 12 months and decayed, missing, or filled surfaces (dmfs) at 30 and 48 months. Methods: Data are from a longitudinal, multisite study with clinical dental examinations conducted at 12, 30, and 48 months of age. Spearman correlation and chi-square tests assessed relationships between teeth present at 12 months and dmfs at 30 (n equals 1,062) and 48 months (n equals 985). Results: Spearman correlations were weak but significant for both 30- and 48-month time points (R equals 0.066, P=0.032; R equals 0.093, P=0.004, respectively). Mantel-Haenszel chi-square analyses of categories of teeth present at 12 months (zero, one to four, five to eight, and greater than or equal to nine) and categories of dmfs at 30 and 48 months (zero, one to two, three to five, six to 15, and greater than or equal to 16) revealed nonsignificant (P=0.326) relationship with 30-month dmfs but a significant (P=0.013) relationship with 48-month dmfs. Conclusion: Results suggest that early tooth eruption is weakly associated with an occurrence of early childhood caries.

Youth Sports Participation Is More Important among Females than Males for Predicting Physical Activity in Early Adulthood: Iowa Bone Development Study.

A gender difference in youth sports and physical activity participation is well documented. However, research is limited to understand potential gender difference in the long-term effects of youth sports participation. The study aim was to compare the likelihood of meeting the aerobic Physical Activity Guidelines (PAG) in early adulthood by youth sports participation patterns among females and males. The study sample included 582 Iowa Bone Development Study participants (Iowa, USA). Participation in organized sports was assessed using a physical activity questionnaire 19 times on average between age 6 and 17 years. Accelerometer and dual-energy X-ray absorptiometry assessments were conducted at an average age of 23 years. Group-based trajectory analysis was conducted to identify youth sports participation trajectory patterns. Multivariable logistic regression analysis was conducted to examine the association between youth sports participation patterns and meeting the PAG in adulthood. We identified three youth sports participation patterns: "continuous participation," "drop-out," and "no participation." Females in the continuous participation group were more likely to meet the aerobic PAG at age 23 years, compared to females in the no-participation group (OR = 2.63; 95% CI = 1.05, 6.55) or the drop-out group (OR = 2.55; 95% CI = 1.38, 4.69). However, among males, youth sports participation patterns were not significantly associated with meeting the aerobic PAG at age 23 years. In conclusion, this study suggests that youth sports participation could be more important among females than males for predicting physical activity in early adulthood.

Effects of fluoride intake on cortical and trabecular bone microstructure at early adulthood using multi-row detector computed tomography (MDCT).

PURPOSE: The aim of this study was to examine the effects of period-specific and cumulative fluoride (F) intake on bone at the levels of cortical and trabecular bone microstructural outcomes at early adulthood using emerging multi-row detector computed tomography (MDCT)-based novel techniques. METHODS: Ultra-high resolution MDCT distal tibia scans were collected at age 19 visits under the Iowa Bone Development Study (IBDS), and cortical and trabecular bone microstructural outcomes were computed at the distal tibia using previously validated methods. CT scans of a tissue characterization phantom were used to calibrate CT numbers (Hounsfield units) into bone mineral density (mg/cc). Period-specific and cumulative F intakes from birth up to the age of 19 years were assessed for IBDS participants through questionnaire, and their relationships with MDCT-derived bone microstructural outcomes were examined using bivariable and multivariable analyses, adjusting for height, weight, maturity offset (years since age of peak height velocity (PHV)), physical activity (questionnaire for adolescents (PAQ-A)), healthy eating index version 2010 (HEI-2010) scores, and calcium and protein intakes. RESULTS: MDCT distal tibia scans were acquired for 324 participants from among the total of 329 participants at age 19 visits. No motion artifacts were observed in any MDCT scans, and all images were successfully processed to measure cortical and trabecular bone microstructural outcomes. At early adulthood, males were observed to have stronger trabecular bone microstructural features, as well as thicker cortical bone (p < 0.01), as compared to age-similar females; however, females were found to have less cortical bone porosity as compared to males. Among participants with available F intake estimates (75 to 91% of the 324 with MDCT scans, depending on the period-specific F intake measure), no statistically significant associations were detected between any period-specific or cumulative F intake and bone microstructural outcomes of the tibia at the p < 0.01 level. Only for females, statistically suggestive associations (p < 0.05) were found between recent F intake (from 14 to 19 years) and trabecular mean plate width and trabecular thickness at the tibia. Those associations became somewhat weaker, but still statistically suggestive, for trabecular thickness in fully adjusted analysis with height, weight, PHV, calcium and protein intake, and HEI-2010 and PAQ-A scores as covariates. CONCLUSION: The findings show that the effects of lifelong or period-specific F intake from combined sources for adolescents typical to the United States Midwest region are not strongly associated with bone microstructural outcomes at age 19 years. These findings are generally consistent with previously reported results of IBDS analyses, which further confirms that effects of lifelong or period-specific F intake on skeletons in early adulthood are absent or weak, even at the levels of cortical and trabecular bone microstructural details.

Analyzing longitudinal clustered count data with zero inflation: Marginal modeling using the Conway-Maxwell-Poisson distribution.

Biological and medical researchers often collect count data in clusters at multiple time points. The data can exhibit excessive zeros and a wide range of dispersion levels. In particular, our research was motivated by a dental dataset with such complex data features: the Iowa Fluoride Study (IFS). The study was designed to investigate the effects of various dietary and nondietary factors on the caries development of a cohort of Iowa school children at the ages of 5, 9, and 13. To analyze the multiyear IFS data, we propose a novel longitudinal method of a generalized estimating equations based marginal regression model. We use a zero-inflated model with a Conway-Maxwell-Poisson (CMP) distribution, which has the flexibility to account for all levels of dispersion. The parameters of interest are estimated through a modified expectation-solution algorithm to account for the clustered and temporal correlation structure. We fit the proposed zero-inflated CMP model and perform a comprehensive secondary analysis of the IFS dataset. It resulted in a number of notable conclusions that also make clinical sense. Additionally, we demonstrated the superiority of this modeling approach over two other popular competing models: the zero-inflated Poisson and negative binomial models. In the simulation studies, we further evaluate the performance of our point estimators, the variance estimators, and that of the large sample confidence intervals for the parameters of interest. It is also demonstrated that our longitudinal CMP model can correctly identify the time-varying dispersion patterns.

Genome-Wide Association Analysis of Longitudinal Bone Mineral Content Data From the Iowa Bone Development Study.

The foundation for osteoporosis risk is, in part, established during childhood, adolescence, and young adulthood, all periods of development when bone mass is acquired rapidly. The relative quantity of bone mass accrued is influenced by both lifestyle and genetic factors, although the genetic component is not yet well understood. The purpose of this study was to use a genome-wide association (GWA) analysis to discover single nucleotide polymorphisms (SNPs) associated with: (1) the sex-specific hip bone mineral content at approximately the age of 19 when the amount of bone accrued is near its peak; and (2) the sex-specific rate of hip bone mineral content accrual during the adolescent growth spurt. The Iowa Bone Development Study, a longitudinal cohort study exploring bone health in children, adolescents, and young adults was the source of data. From this cohort, n = 364 (190 females, 174 males) participants were included in GWA analyses to address (1) and n = 258 participants (125 females and 133 males) were included in GWA analyses to address (2). Twenty SNPS were detected having p < 1.0 × 10-5. Of most biologic relevance were 2 suggestive SNPs (rs2051756 and rs2866908) detected in an intron of the DKK2 gene through the GWA analysis that explored peak bone mass in females.

Moderate-to-vigorous intensity physical activity trajectories during adolescence and young adulthood predict adiposity in young adulthood: The Iowa Bone Development Study.

This study examined the associations of moderate-to-vigorous intensity physical activity (MVPA) trajectories in adolescence through young adulthood with adiposity in young adults. Participants from The Iowa Bone Development Study cohort were longitudinally assessed (N = 297; 57% female). Accelerometry-measured MVPA (min/day) at ages 15 through 23 years, and fat mass and visceral adipose tissue mass indices (kg/m2, g/m2) derived from dual-energy X-ray absorptiometry scans at age 23 years were analyzed. Latent trajectory analyses classified MVPA into two patterns. Multivariable linear regression analyses showed that being in the high MVPA trajectory group was associated with lower fat mass index z-scores. Individuals who were consistently active with high MVPA (vs. moderately active with decreasing MVPA) during adolescence up until early young adulthood had less accumulation of total body adiposity in young adulthood. This study suggests that adopting a consistently active lifestyle throughout adolescence can result in healthier body composition in young adulthood.

Beverage Intakes and Toothbrushing During Childhood Are Associated With Caries at Age 17 Years.

BACKGROUND: Sugar-sweetened beverages (SSBs) have been associated with childhood caries; however, associations among lifelong beverage intakes and adolescent caries have received less attention. OBJECTIVE: To investigate associations between beverage intakes during childhood and adolescence and caries experience at 17 years of age, while adjusting for fluoride intakes and toothbrushing. DESIGN: Descriptive model analyses were conducted on data collected from a longitudinal birth cohort study. PARTICIPANTS/SETTING: Participants included Iowa Fluoride Study members (n = 318) recruited at birth between 1992 and 1995 with at least 6 beverage questionnaires completed from ages 1 to 17 years and a caries examination at age 17. EXPOSURE: Predictors included mean daily milk, juice (100% juice and juice drinks before age 9), SSB (including juice drinks after age 9), and water/sugar-free beverage (SFB) intakes; daily fluoride intakes; and daily toothbrushing frequencies for ages 1 to 17. MAIN OUTCOME MEASURES: The outcome was dental caries count at age 17, adjusted for the number of scored tooth surfaces (decayed and filled surfaces attack rate [DFSAR]). STATISTICAL ANALYSES PERFORMED: Univariable generalized linear models were fit for each predictor and the outcome DFSAR. Multivariable models assessed combined effects of beverage types, fluoride variables, toothbrushing, sex, and baseline socioeconomic status. RESULTS: Based on multivariable models, each 8 oz of additional daily juice and water/SFB decreased expected DFSAR by 53% (95% confidence interval [CI]: 17%-73%) and 29% (95% CI: 7%-46%), respectively, and 8 additional oz SSBs increased expected DFSAR by 42% (95% CI: 5%-92%), after adjustment for other beverage intakes, toothbrushing, total fluoride intake excluding SSB fluoride (non-SSB total fluoride), sex, and baseline socioeconomic status. Each additional daily toothbrushing event decreased expected DFSAR by 43% (95% CI: 14%-62%) after adjustment for beverage intakes, non-SSB total fluoride intake, sex, and baseline SES. CONCLUSIONS: Higher juice and water/SFB intakes and more toothbrushing were associated with lower caries at age 17, while higher SSB intakes were associated with higher caries.

Identification of and Associations among Low, Middle, and High Body Composition Trajectories from Age 5- to 17-Years.

Our objective was to identify sex-specific age 5- to 17-year body composition (body mass index (BMI), % body fat, fat mass index, fat-free mass index) trajectories, compare trajectories assigned using age 5 (AGE5) data to those assigned using all available (ALL) data, and compare BMI assignments to other body composition assignments. Cluster analysis was used to identify low, medium, and high trajectories from body composition measures obtained from dual energy x-ray absorptiometry (DXA) scans at 5, 9, 11, 13, 15, and 17 years in a birth cohort followed longitudinally (n = 469). Moderate agreement was observed for comparisons between AGE5 data and ALL data cluster assignments for each body composition measure. Agreement between cluster assignments for BMI and other body composition measures was stronger using ALL data than using AGE5 data. Our results suggest that BMI, % body fat, fat mass index, and fat free mass index trajectories are established during early childhood, and that BMI is a reasonable predictor of body composition appropriate to track obesity in public health and clinical settings.