[Show abstract][Hide abstract] ABSTRACT: Osteoporosis is a common bone disease associated with increased risk of low-trauma fractures leading to substantial morbidity, mortality, and financial costs. Clinically, osteoporosis is defined by low bone mineral density (BMD); however, increasing evidence suggests that trabecular bone (TB) microarchitectural quality is an important determinant of bone strength and fracture risk. A tensor scale based algorithm for in vivo characterization of TB plate-rod microarchitecture at the distal tibia using multirow detector CT (MD-CT) imaging is presented and its performance and applications are examined.
The tensor scale characterizes individual TB on the continuum between a perfect plate and a perfect rod and computes their orientation using optimal ellipsoidal representation of local structures. The accuracy of the method was evaluated using computer-generated phantom images at a resolution and signal-to-noise ratio achievable in vivo. The robustness of the method was examined in terms of stability across a wide range of voxel sizes, repeat scan reproducibility, and correlation between TB measures derived by imaging human ankle specimens under ex vivo and in vivo conditions. Finally, the application of the method was evaluated in pilot human studies involving healthy young-adult volunteers (age: 19 to 21 yr; 51 females and 46 males) and patients treated with selective serotonin reuptake inhibitors (SSRIs) (age: 19 to 21 yr; six males and six females).
An error of (3.2% ± 2.0%) (mean ± SD), computed as deviation from known measures of TB plate-width, was observed for computer-generated phantoms. An intraclass correlation coefficient of 0.95 was observed for tensor scale TB measures in repeat MD-CT scans where the measures were averaged over a small volume of interest of 1.05 mm diameter with limited smoothing effects. The method was found to be highly stable at different voxel sizes with an error of (2.29% ± 1.56%) at an in vivo voxel size as compared to the original ex vivo voxel size. Tensor scale measures derived from imaging under in vivo and ex vivo conditions with significantly different modulation transfer function, i.e., difference in "true resolution," showed strong linear correlation (r = 0.92). The study of healthy volunteers shows that, after adjustment for height and weight, males have a 14% higher mean TB plate-width as compared to females (p < 0.05). SSRI-treated patients have 12.5% lower mean TB plate-width (p = 0.052) as compared to age-similar and sex-, height-, and weight-matched healthy controls. In contrast, the observed group difference in dual-energy x-ray absorptiometry (DXA)-derived hip BMD was 10.5% between males and females and only 5.04% between healthy controls and patients on SSRIs.
Tensor scale analysis of MD-CT images yields accurate and reproducible characterization of TB plate-rod microarchitecture that may be more sensitive than DXA-derived BMD to sex differences and to the skeletal changes associated with medical conditions or their treatments.
Medical Physics 09/2015; 42(9):5410. DOI:10.1118/1.4928481 · 2.64 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Cortical bone supports and protects human skeletal functions and plays an important role in determining bone strength and fracture risk. Cortical bone segmentation at a peripheral site using multirow-detector CT (MD-CT) imaging is useful for in vivo assessment of bone strength and fracture risk. Major challenges for the task emerge from limited spatial resolution, low signal-to-noise ratio, presence of cortical pores, and structural complexity over the transition between trabecular and cortical bones. An automated algorithm for cortical bone segmentation at the distal tibia from in vivo MD-CT imaging is presented and its performance and application are examined.
The algorithm is completed in two major steps-(1) bone filling, alignment, and region-of-interest computation and (2) segmentation of cortical bone. After the first step, the following sequence of tasks is performed to accomplish cortical bone segmentation-(1) detection of marrow space and possible pores, (2) computation of cortical bone thickness, detection of recession points, and confirmation and filling of true pores, and (3) detection of endosteal boundary and delineation of cortical bone. Effective generalizations of several digital topologic and geometric techniques are introduced and a fully automated algorithm is presented for cortical bone segmentation.
An accuracy of 95.1% in terms of volume of agreement with manual outlining of cortical bone was observed in human MD-CT scans, while an accuracy of 88.5% was achieved when compared with manual outlining on postregistered high resolution micro-CT imaging. An intraclass correlation coefficient of 0.98 was obtained in cadaveric repeat scans. A pilot study was conducted to describe gender differences in cortical bone properties. This study involved 51 female and 46 male participants (age: 19-20 yr) from the Iowa Bone Development Study. Results from this pilot study suggest that, on average after adjustment for height and weight differences, males have thicker cortex (mean difference 0.33 mm and effect size 0.92 at the anterior region) with lower bone mineral density (mean difference -28.73 mg/cm(3) and effect size 1.35 at the posterior region) as compared to females.
The algorithm presented is suitable for fully automated segmentation of cortical bone in MD-CT imaging of the distal tibia with high accuracy and reproducibility. Analysis of data from a pilot study demonstrated that the cortical bone indices allow quantification of gender differences in cortical bone from MD-CT imaging. Application to larger population groups, including those with compromised bone, is needed.
Medical Physics 08/2015; 42(8):4553. DOI:10.1118/1.4923753 · 2.64 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The diverse developmental patterns of obesogenic behaviors during childhood and adolescence can be better understood by using new analytic approaches to assess the heterogeneity in variation during growth and development and to map the clustering of behavior patterns.
To identify distinct trajectories of daily time spent in moderate- to vigorous-intensity physical activity (MVPA) from ages 5 to 19 years and to examine the associations of MVPA trajectories with sports participation and television viewing trajectories.
Cohort members in the prospective population-based Iowa Bone Development Study participated in MVPA assessments via accelerometry from September 16, 1998, to December 9, 2013, at ages 5, 8, 11, 13, 15, 17, and 19 years and completed a questionnaire every 6 months on sports participation and daily time spent in television viewing.
Trajectories of MVPA (minutes per day), participation in organized sports (yes or no), and television viewing time (hours per day).
Based on the data from 537 participants (50.1% females; 94.6% white), we identified 4 MVPA trajectories: consistently inactive (14.9%), consistently active (18.1%), decreasing moderate physical activity (52.9%), and substantially decreasing high physical activity (14.1%). All participants in the consistently inactive trajectory also followed a trajectory of no participation in sports. The consistently active trajectory was associated with decreasing an already low television viewing trajectory (P < .001).
This study provided a nuanced look at the known decrease in MVPA during childhood and adolescence. Sports participation could be a critical way to avoid the consistently inactive pattern. Most important, we identified a subset of participants who maintained a seemingly healthy level of MVPA from childhood to young adulthood. The developmental pathways of physical activity and television viewing behaviors could be related. Additional studies should examine the determinants and health consequences of these specific MVPA trajectories.
[Show abstract][Hide abstract] ABSTRACT: To assess association between lower body muscle power and bone strength, as well as the mediating effect of muscle cross-sectional area (MCSA) on that association.
Participants (N=141 males; 162 females) were approximately 17 years. Muscle power was predicted using vertical jump and the Sayers equation. Using peripheral quantitative computed tomography (pQCT), bone strength indices were obtained at two locations of the tibia, corresponding to primary stressors acting upon each site: bone strength index for compression (BSI) at the distal 4% site; density-weighted polar section modulus strength-strain index [SSIp] and cortical bone area (CoA) at the 66% mid-shaft site for torsion. Muscle cross-sectional area (MCSA) was measured at the 66% site. Pearson bivariate and partial correlation coefficients were estimated to quantify the strength of the associations among variables. Direct and indirect mediation model effects were estimated and 95% bootstrap confidence intervals were constructed to test the causal hypothesis. Height and maturity were examined as covariates.
Pearson correlation coefficients among muscle power, MCSA, and bone strength were statistically significant (p<0.01) and ranged from r=0.54 to 0.78. After adjustment for covariates, associations were reduced (r=0.37 to 0.69) (p<0.01). Mediation models for males for BSI, SSIp, and CoA accounted for 38%, 66%, and 54% of the variance in bone strength, respectively. Models for females for BSI, SSIp, and CoA accounted for 46%, 77%, and 66% of the variance, respectively.
We found strong and consistent associations, as well as direct and indirect pathways, among muscle power, MCSA, and tibia strength. These results support the use of muscle power as a component of health-related fitness in bone health interventions for older adolescents.
Medicine & Science in Sports & Exercise 02/2015; 47(10). DOI:10.1249/MSS.0000000000000648 · 3.98 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Aging is a natural process involving complex interplay between environment, metabolism, and genes. Sirtuin genes and their downstream targets have been associated with lifespan in numerous organisms from nematodes to humans. Several target proteins of the sirtuin genes are key sensors and/or effectors of oxidative stress pathways including FOXO3, SOD3, and AKT1. To examine the relationship between single nucleotide polymorphisms (SNP) at candidate genes in these pathways and human lifespan, we performed a molecular epidemiologic study of an elderly cohort (≥65 years old.). Using age at death as a continuous outcome variable and assuming a co-dominant genetic model within the framework of multi-variable linear regression analysis, the genotype-specific adjusted mean age at death was estimated for individual SNP genotypes while controlling for age-related risk factors including smoking, body mass index, alcohol consumption and co-morbidity. Significant associations were detected between human lifespan and SNPs in genes SIRT3, SIRT5, SIRT6, FOXO3 and SOD3. Individuals with either the CC or CT genotype at rs107251 within SIRT6 displayed >5-year mean survival advantages compared to the TT genotype (5.5 and 5.9 years, respectively; q-value = 0.012). Other SNPs revealed genotype-specific mean survival advantages ranging from 0.5 to 1.6 years. Gender also modified the effect of SNPs in SIRT3, SIRT5 and AKT1 on lifespan. Our novel findings highlight the impact of sirtuins and sirtuin-related genotypes on lifespan, the importance of evaluating gender and the advantage of using age as a continuous variable in analyses to report mean age at death.
PLoS ONE 12/2014; 9(12):e115616. DOI:10.1371/journal.pone.0115616 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
Adverse associations between maternal pesticide exposure and neural tube defects (NTDs) have been suggested but not consistently observed. This study used data from the multisite National Birth Defects Prevention Study to examine associations between maternal periconceptional (1 month preconception through 2 months postconception) occupational pesticide exposure and NTDs.
Mothers of 502 NTD cases and 2950 unaffected live-born control infants with estimated delivery dates from 1997 through 2002 were included. Duration, categorical intensity scores, and categorical frequency scores for pesticide classes (e.g., insecticides) were assigned using a modified, literature-based job-exposure matrix and maternal-reported occupational histories. Adjusted odds ratios (aORs) and 95% confidence intervals were estimated based on fitted multivariable logistic regression models that described associations between maternal periconceptional occupational pesticide exposure and NTDs. The aORs were estimated for pesticide exposure (any [yes/no] and cumulative exposure [intensity × frequency × duration] to any pesticide class, each pesticide class, or combination of pesticide classes) and all NTD cases combined and NTD subtypes.
Positive, but marginally significant or nonsignificant, aORs were observed for exposure to insecticides + herbicides for all NTD cases combined and for spina bifida alone. Similarly, positive aORs were observed for any exposure and cumulative exposure to insecticides + herbicides + fungicides and anencephaly alone and encephalocele alone. All other aORs were near unity.
Pesticide exposure associations varied by NTD subtype and pesticide class. Several aORs were increased, but not significantly. Future work should continue to examine associations between pesticide classes and NTD subtypes using a detailed occupational pesticide exposure assessment and examine pesticide exposures outside the workplace.
Birth Defects Research Part A Clinical and Molecular Teratology 11/2014; 100(11). DOI:10.1002/bdra.23293 · 2.09 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Purpose: Greater visceral fat (VF) has been associated with with lower bone measures in youth, though this relationship has not been evaluated longitudinally. The purpose of this study was to determine if VF is negatively associated with bone parameters in overweight and obese adolescents from age 11-17.
Methods: Iowa Bone Development Study participants underwent peripheral quantitative computed tomography (pQCT) scans of the radius and tibia and whole body dual energy x-ray absorptiometry (DXA) scans every 2 years from age 11-17. Eligible participants were overweight or obese at age 11 according to CDC BMI percentiles and had age 11 baseline scans and age 15 or 17 follow-up. VF area (cm2) was estimated from whole body DXA scans using Apex 4.0 software (Hologic, Inc). Gender specific analyses evaluated the relationship between VF and bone development with growth models using biological age (visit age – age of peak height velocity) as the time variable adjusted for limb length and lean mass. Results are presented as standardized parameter estimates.
Results: Eligible participants included 42 girls(45% obese) and 52 boys (35% obese) with a mean age at baseline of 11.2±0.3 years. In girls, greater VF was associated with thinner cortical bone and lower strength-strain index (SSI) at the radius (20% site), but not tibia (Table). In boys, greater VF was associated with lower density and strength at the predominantly trabecular bone site (4%) at the tibia but not radius. At the cortical site in boys (20%), greater VF was associated with thinner bones at the radius with no significant associations at the tibia. In sensitivity analyses restricted to obese participants, results remained relatively unchanged in girls. In boys, the relationship between VF and SSI (20% site) became significant (-0.12±0.05, p=0.0260) while parameter estimates for associations at the 4% tibial site were attenuated and no longer reached significance (BMD: -0.14±0.08, p=0.11; BSI: -0.17±0.09, p=0.07).
Conclusions: Greater VF is associated with lower cortical bone strength at the non-weight-bearing radius but not at the tibia where greater mechanical loading may attenuate the negative relationship. Lower trabecular bone strength at the tibia with greater VF in boys may be a reflection of more rapid growth at that site. These results suggest the bone-fat relationship may vary depending on adiposity and bone site and explain previous, conflicting reports on this relationship.
American Society for Bone and Mineral Research 2014 Annual Meeting, Houston, Texas, USA; 09/2014
[Show abstract][Hide abstract] ABSTRACT: This study examined the association between physical activity (PA) and bone mineral content (BMC; gram) from middle childhood to middle adolescence and compared the impact of vigorous-intensity PA (VPA) over moderate- to vigorous-intensity PA (MVPA). Participants from the Iowa bone development study were examined at ages 5, 8, 11, 13, and 15 years (n = 369, 449, 452, 410, and 307, respectively). MVPA and VPA (minutes per day) were measured using ActiGraph accelerometers. Anthropometry was used to measure body size and somatic maturity. Spine BMC and hip BMC were measured via dual-energy x-ray absorptiometry. Sex-specific multi-level linear models were fit for spine BMC and hip BMC, adjusted for weight (kilogram), height (centimeter), linear age (year), non-linear age (year(2)), and maturity (pre peak height velocity vs. at/post peak height velocity). The interaction effects of PA × maturity and PA × age were tested. We also examined differences in spine BMC and hip BMC between the least (10th percentile) and most (90th percentile) active participants at each examination period. Results indicated that PA added to prediction of BMC throughout the 10-year follow-up, except MVPA, did not predict spine BMC in females. Maturity and age neither modify the PA effect for males nor females. At age 5, the males at the 90th percentile for VPA had 8.5% more hip BMC than males in the 10th percentile for VPA. At age 15, this difference was 2.0%. Females at age 5 in the 90th percentile for VPA had 6.1% more hip BMC than those in the 10th percentile for VPA. The age 15 difference was 1.8%. VPA was associated with BMC at weight-bearing skeletal sites from childhood to adolescence, and the effect was not modified by maturity or age. Our findings indicate the importance of early and sustained interventions that focus on VPA. Approaches focused on MVPA may be inadequate for optimal bone health, particularly for females.
Frontiers in Endocrinology 07/2014; 5:112. DOI:10.3389/fendo.2014.00112
[Show abstract][Hide abstract] ABSTRACT: Background:
Correction for soft tissue signal attenuation can improve the diagnostic accuracy of single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI). The aim of this study was to correlate SPECT-MPI findings with clinical outcomes in patients who underwent stress imaging in the supine position, who also underwent "second look" stress imaging in the prone position.
Patients without perfusion abnormalities were considered Normal (N = 270). Those with apparent supine stress perfusion abnormalities which all resolved during prone imaging formed the Normal-Prone group (N = 309). Patients with matched perfusion abnormalities during both supine and prone stress imaging were considered Abnormal (N = 169).
During follow-up (187 ± 96 days), utilization rates for invasive coronary angiography were similar for Normal vs Normal-Prone patients (3.5% vs 3.8%; P = NS), but were significantly higher in Abnormal patients (42.4%, P < .0001). Coronary revascularization occurred in 0.78%, 0.64%, and 17.7% of Normal, Normal-Prone, and Abnormal patients, respectively (P < .001). Cardiac death or myocardial infarction occurred in 2.2%, 2.3%, and 6.3% of Normal, Normal-Prone, and Abnormal patients, respectively (P = .02).
Second look SPECT-MPI identifies patients at low risk for death or myocardial infarction, who infrequently require invasive coronary angiography.
[Show abstract][Hide abstract] ABSTRACT: Background / Purpose:
Substantial evidence exists to indicate bidirectional relationships between obesity and depressive disorders and the importance of fat distribution to this relationship. This analysis used a well-characterized sample of individuals in late adolescence to determine the association between depressive illness and fat distribution.
In adolescents, relationships between central adiposity and major depressive disorder (MDD) may be confined to those who are overweight/obese. Despite the high co-morbidity of anxiety and depressive disorders, only the latter appeared to be significantly associated with adiposity.
69th Society of Biological Psychiatry Annual Meeting 2014; 06/2014
[Show abstract][Hide abstract] ABSTRACT: Background Physical activity improves bone strength and reduces the risk for osteoporotic fractures. However, there are substantial gaps in our knowledge as to when, how and how much activity is optimal for bone health.
Purpose In this cohort study, we examined developmental trajectories of objectively measured physical activity from childhood to adolescence to discern if moderate-and-vigorous intensity physical activity (MVPA) predicts bone strength.
Methods Starting at age 5 and continuing at 8, 11, 13, 15 and 17 years, Iowa Bone Development Study participants (n=530) wore an accelerometer for 3–5 days. At age 17, we assessed dual X-ray energy absorptiometry outcomes of mass and estimated geometry (femoral neck cross-sectional area and section modulus). We also assessed geometric properties (bone stress index and polar moment of inertia) of the tibia using peripheral computer quantitative tomography. Latent class modelling was used to construct developmental trajectories of MVPA from childhood to late adolescence. General linear models were used to examine the trajectory groups as predictors of age 17 bone outcomes.
Results Girls and boys who accumulated the most MVPA had greater bone mass and better geometry at 17 years when compared to less active peers. The proportion of participants achieving high levels of MVPA throughout childhood was very low (<6% in girls) and by late adolescence almost all girls were inactive.
Conclusions Bone health benefits of physical activity are not being realised due to low levels of activity for most youth, especially in girls.
British Journal of Sports Medicine 05/2014; 48(13). DOI:10.1136/bjsports-2014-093574 · 5.03 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective
To examine associations among age, physical activity (PA), and birth cohort on body mass index (BMI) percentiles in men.
Design and Methods
Longitudinal analyses using quantile regression were conducted among men with ≥ two examinations between 1970 and 2006 from the Aerobics Center Longitudinal Study (n=17,759). Height and weight were measured; men reported their PA and were categorized as inactive, moderately or highly active at each visit. Analyses allowed for longitudinal changes in PA.
BMI was greater in older than younger men and in those born in 1960 than those born in 1940. Inactive men gained weight significantly more rapidly than active men. At the 10th percentile, increases in BMI among inactive, moderately active, and highly active men were 0.092, 0.078, and 0.069 kg/m2 per year of age, respectively. The 10th percentile increased by 0.081 kg/m2 per birth year and by 0.180 kg/m2 at the 90th percentile, controlling for age.
Although BMI increased with age, PA reduced the magnitude of the gradient among active compared to inactive men. Regular PA had an important, protective effect against weight gain. This study provides evidence of the utility of quantile regression to examine the specific causes of the obesity epidemic.
[Show abstract][Hide abstract] ABSTRACT: Objective:
Second-generation antipsychotics (SGAs) cause weight gain and cardiometabolic abnormalities in children and adolescents. Less well-investigated is the outcome of these adverse events following SGA discontinuation, which we examined.
Medically healthy 7 to 17-year-old patients treated with risperidone for ≥6 months were enrolled and returned for follow-up, 1.5 years later. Treatment history was extracted from the medical and pharmacy records. Anthropometric and laboratory measurements were obtained at each research visit. Multivariable linear regression analysis and Fisher's exact test were used to compare participants who remained on risperidone at follow-up (Risp Cont Group) with those who had discontinued SGA treatment (SGA Disc Group) and those who had switched to another SGA (SGA Cont Group). Correlational analyses examined the association between change in age-sex specific body mass index (BMI) z score between study entry and follow-up and change in cardiometabolic outcomes.
The sample consisted of 101 participants (93% male) with a mean age of 11.7±2.6 years at study entry. The majority had an externalizing disorder and received 0.03±0.02 mg/kg/day of risperidone, for 2.5±1.6 years. At follow-up, 18% (n=18) were in the SGA Disc Group and 9% (n=9) were in the SGA Cont Group. BMI z score decreased in the SGA Disc Group, remained unchanged in the Risp Cont Group (n=74), and increased in the SGA Cont Group. Importantly, the change in BMI z score between study entry and follow-up was significantly correlated with the change in systolic and diastolic blood pressure z scores, heart rate, waist circumference, percent body fat, inflammatory markers, fasting total insulin, homeostatic model assessment insulin resistance index (HOMA-IR), C-peptide, total, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) cholesterol, triglycerides, triglycerides/HDL ratio, and leptin.
Following several years of treatment, risperidone discontinuation is associated with a reversal of the excessive weight gain, mediated by a negative energy balance, and a corresponding improvement in cardiometabolic parameters.
Journal of child and adolescent psychopharmacology 04/2014; 24(3):120-9. DOI:10.1089/cap.2013.0126 · 2.93 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Choanal atresia causes serious posterior nasal obstruction. This defect is the leading cause of nasal surgery in newborns, although its etiology is largely unknown. Data from the National Birth Defects Prevention Study, a population-based case-control study, were used to examine associations between maternal self-reports of exposures and occurrence of choanal atresia in their offspring. Overall, 117 case and 8350 control mothers with deliveries from 1997-2007 provided telephone interview reports of pre-pregnancy (one year before conception) and periconceptional (one month before through three months after conception) exposures. Exposures analyzed were pre-pregnancy dietary intake, pre-pregnancy and periconceptional caffeine consumption, and periconceptional cigarette smoking, alcohol drinking, and medication use. Independent associations between each exposure and all choanal atresia cases combined (n=117) and isolated choanal atresia cases (those without additional unrelated major defects; n=61) were examined. Odds ratios (ORs), both unadjusted (uORs) and adjusted (aORs) for potential confounders, and 95% confidence intervals (CI)s were estimated using unconditional logistic regression analysis. For all choanal atresia cases combined, positive associations were observed with maternal pre-pregnancy intake in the highest quartile for vitamin B-12 (aOR=1.9; CI=1.1,3.1), zinc (aOR=1.7; CI=1.0,3.1), and niacin (aOR=1.8; CI=1.0,3.1), and intake in the lowest quartile for methionine (aOR=1.6; CI=1.0,2.6) and vitamin D (aOR=1.6; CI=1.0,2.4) compared to intake in the two intermediate quartiles combined. Further, a positive association was observed with periconceptional use of thyroid medications (uOR=2.6; CI=1.0,6.3) compared to no use of such medications. Among isolated choanal atresia cases, negative associations were observed for pantothenic acid (aOR=0.4; CI=0.2,0.9) and fat (aOR=0.5; 95% CI=0.2,1.0) intake in the lowest quartile compared to that in the intermediate quartiles, and positive associations were observed for periconceptional cigarette smoking (aOR=2.3; CI=1.1,4.7) compared to no smoking and pre-pregnancy daily coffee intake of 3 or more cups (aOR=2.5; CI=1.1,5.6) compared to intake of less than 1 cup per day. The positive association for periconceptional exposure to thyroid medications also persisted for isolated choanal atresia cases (uOR=4.0; CI=1.1,11.2). Because of the large number of associations tested, these findings may be due to chance. Alternatively, they may contribute new hypotheses regarding the etiology of choanal atresia; thus, requiring replication in additional studies.
European journal of medical genetics 04/2014; 57(5). DOI:10.1016/j.ejmg.2014.02.010 · 1.47 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Adult bone diseases, especially osteoporosis, lead to increased risk of fracture which in turn is associated with substantial morbidity, mortality, and financial costs. Clinically, osteoporosis is defined by low bone mineral density (BMD); however, increasing evidence suggests that the micro-architectural quality of trabecular bone (TB) is an important determinant of bone strength and fracture risk. Accurate measures of TB thickness and marrow spacing is of significant interest for early diagnosis of osteoporosis or treatment effects. Here, we present a new robust algorithm for computing TB thickness and marrow spacing at a low resolution achievable in vivo. The method uses a star-line tracing technique that effectively deals with partial voluming effects of in vivo imaging with voxel size comparable to TB thickness. Also, the method avoids the problem of digitization associated with conventional algorithms based on sampling distance transform along skeletons. Accuracy of the method was examined using computer-generated phantom images while the robustness of the method was evaluated on human ankle specimens in terms of stability across a wide range of voxel sizes, repeat scan reproducibility under in vivo conditions, and correlation between thickness values computed at ex vivo and in vivo imaging resolutions. Also, the sensitivity of the method was examined by evaluating its ability to predict the bone strength of cadaveric specimens. Finally, the method was evaluated in a human study involving 40 healthy young-adult volunteers (age: 19 to 21 years; 20 males and 20 females) and ten athletes (age: 19 to 21 years; 6 males and 4 females). Across a wide range of voxel sizes, the new method is significantly more accurate and robust as compared to conventional methods. Both TB thickness and marrow spacing measures computed using the new method demonstrated strong associations (R2 2 [0:83; 0:87]) with bone strength. Also, the TB thickness and marrow spacing measures allowed discrimination between male and female volunteers (p 2 [0:01; 0:04]) as well as between athletes and non-athletes (p 2 [0:005; 0:03]).
[Show abstract][Hide abstract] ABSTRACT: Controversy persists concerning the impact of community water fluoridation on bone health in adults, and few studies have assessed relationships with bone at younger ages. Ecological studies of fluoride's effects showed some increase in bone mineral density of adolescents and young adults in areas with fluoridated water compared with non-fluoridated areas. However, none had individual fluoride exposure measures. To avoid ecological fallacy and reduce bias, we assessed associations of average daily fluoride intake from birth to age 15 yr for Iowa Bone Development Study cohort members with age 15 yr dual-energy x-ray absorptiometry (DXA) bone outcomes (whole body, lumbar spine, and hip), controlling for known determinants (including daily calcium intake, average daily time spent in moderate-to-vigorous intensity physical activity, and physical maturity). Mean (SD) daily fluoride intake was 0.66 mg (0.24) for females and 0.78 mg (0.30) for males. We found no significant relationships between daily fluoride intake and adolescents' bone measures in adjusted models (for 183 females, all p values ≥ .10 and all partial R(2) ≤ 0.02; for 175 males, all p values ≥ .34 and all partial R(2) ≤ 0.01). The findings suggest that fluoride exposures at the typical levels for most US adolescents in fluoridated areas do not have significant effects on bone mineral measures.
Journal of dental research 01/2014; 93(4). DOI:10.1177/0022034514520708 · 4.14 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Chronic recurrent multifocal osteomyelitis (CRMO) is a human autoinflammatory disorder that primarily affects bone. Missense mutation (L98P) of proline-serine-threonine phosphatase-interacting protein 2 (Pstpip2) in mice leads to a disease that is phenotypically similar to CRMO called chronic multifocal osteomyelitis (cmo). Here we show that deficiency of IL-1RI in cmo mice resulted in a significant reduction in the time to onset of disease as well as the degree of bone pathology. Additionally, the proinflammatory cytokine IL-1β, but not IL-1α, played a critical role in the pathology observed in cmo mice. In contrast, disease in cmo mice was found to be independent of the nucleotide-binding domain, leucine-rich repeat-containing family, pyrin domain-containing 3 (NLRP3) inflammasome as well as caspase-1. Neutrophils, but not bone marrow-derived macrophages, from cmo mice secreted increased IL-1β in response to ATP, silica, and Pseudomonas aeruginosa compared with neutrophils from WT mice. This aberrant neutrophil response was sensitive to inhibition by serine protease inhibitors. These results demonstrate an inflammasome-independent role for IL-1β in disease progression of cmo and implicate neutrophils and neutrophil serine proteases in disease pathogenesis. These data provide a rationale for directly targeting IL-1RI or IL-1β as a therapeutic strategy in CRMO.
Proceedings of the National Academy of Sciences 01/2014; 111(3). DOI:10.1073/pnas.1318685111 · 9.67 Impact Factor