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Objective: This study aimed to investigate how skeletal muscle attenuation and adipose tissue (AT) attenuation of the quadriceps, hamstrings, paraspinal muscle groups and the psoas muscle vary according to the targeted muscles, sex, and age., Design: Population-based cross-sectional study., Setting: Community-dwelling old population in Reykjavik, Iceland., Subjects: A total of 5331 older adults (42.8% women), aged 66-96 years from the Age, Gene/Environment Susceptibility (AGES)- Reykjavik Study, who participated in the baseline visit (between 2002 and 2006) and had valid thigh and abdominal computed tomography (CT) scans were studied., Methods: Muscle attenuation and AT attenuation of the quadriceps, hamstrings, paraspinal muscle groups and the psoas muscle were determined using CT. Linear mixed model analysis of variance was performed for each sex, with skeletal muscle or AT attenuation as the dependent variable., Results: Muscle attenuation decreased, and AT attenuation increased with age in both sexes, and these differences were specific for each muscle, although not in all age groups. Age-related differences in muscle and AT attenuation varied with specific muscle. In general, for both sexes, skeletal muscle attenuation of the hamstrings declined more than average with age. Men and women displayed a different pattern in the age differences in AT attenuation for each muscle., Conclusions: Our data support the hypotheses that skeletal muscle attenuation decreases, and AT attenuation increases with aging. In addition, our data add new evidence, supporting that age-related differences in skeletal muscle and AT attenuation vary between muscles., (Copyright © 2021 Elsevier Inc. All rights reserved.)

In this case-cohort study, we used data-driven computational anatomy approaches to assess within and between sex spatial differences in proximal femoral bone characteristics in relation to incident hip fracture. One hundred male and 234 female incident hip fracture cases, and 1047 randomly selected noncase subcohort participants (562 female) were chosen from the population-based AGES-Reykjavik study (mean age of 77 years). The baseline -i.e. before hip fracture- hip quantitative computed tomography scans of these subjects were analyzed using voxel-based morphometry, tensor-based morphometry, and surface-based statistical parametric mapping to assess the spatial distribution of volumetric bone mineral density (vBMD), internal structure, and cortical bone properties (thickness, vBMD and trabecular vBMD adjacent to the endosteal surface) of the proximal femur, respectively, in relation to incident hip fracture. Results showed that in both men and women: 1) the superior aspect of the femoral neck and the trochanteric region (except for cortical bone thickness) were consistently identified as being associated with incident hip fracture, and 2) differences in bone properties between noncases and incident hip fracture cases followed similar trends, were located at compatible regions, and manifested heterogeneity in the spatial distribution of their magnitude with focal regions showing larger differences. With respect to sex differences, most of the regions with a significant interaction between fracture group and sex showed: 1) differences of greater magnitude in men between noncases and incident hip fracture cases with different spatial distributions for all bone properties with the exception of cortical bone thickness, and 2) that while most of these regions showed better bone quality in male cases than in female cases, female cases showed higher vBMD in the principal compressive group and higher endotrabecular vBMD at several regions including the anterior, posterior, and lateral aspects of the proximal femur. These findings indicate the value of these image analysis techniques by providing unique information about the specific patterns of bone deterioration associated with incident hip fracture and their sex differences, highlighting the importance of looking to men and women separately in the assessment of hip fracture risk., (Copyright © 2018. Published by Elsevier Inc.)

Background: Knowledge of adipose composition in relation to mortality may help delineate inconsistent relationships between obesity and mortality in old age. We evaluated relationships between abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) density, mortality, biomarkers, and characteristics., Methods: VAT and SAT density were determined from computed tomography scans in persons aged 65 and older, Health ABC (n = 2,735) and AGES-Reykjavik (n = 5,131), and 24 nonhuman primates (NHPs). Associations between adipose density and mortality (4-13 years follow-up) were assessed with Cox proportional hazards models. In NHPs, adipose density was related to serum markers and tissue characteristics., Results: Higher density adipose tissue was associated with mortality in both studies with adjustment for risk factors including adipose area, total fat, and body mass index. In women, hazard ratio and 95% CI for the densest quintile (Q5) versus least dense (Q1) for VAT density were 1.95 (1.36-2.80; Health ABC) and 1.88 (1.31-2.69; AGES-Reykjavik) and for SAT density, 1.76 (1.35-2.28; Health ABC) and 1.56 (1.15-2.11; AGES-Reykjavik). In men, VAT density was associated with mortality in Health ABC, 1.52 (1.12-2.08), whereas SAT density was associated with mortality in both Health ABC, 1.58 (1.21-2.07), and AGES-Reykjavik, 1.43 (1.07-1.91). Higher density adipose tissue was associated with smaller adipocytes in NHPs. There were no consistent associations with inflammation in any group. Higher density adipose tissue was associated with lower serum leptin in Health ABC and NHPs, lower leptin mRNA expression in NHPs, and higher serum adiponectin in Health ABC and NHPs., Conclusion: VAT and SAT density provide a unique marker of mortality risk that does not appear to be inflammation related.

Background: Aging skeletal muscle is characterized not only by a reduction in size (sarcopenia) and strength but also by an increase in fatty infiltration (myosteatosis). An effective countermeasure to sarcopenia is resistance exercise; however, its effect on fatty infiltration is less clear., Objective: To examine in resistance-trained older persons whether muscle attenuation, a noninvasive measure of muscle density reflecting intramuscular lipid content, is altered with training status., Methods: Thirteen healthy community-dwelling men and women aged 65-83 years (body mass index 27.0+/-1.2, mean+/-SE) had computed-tomography scans of the mid-thigh performed following 24 weeks of training, 24 weeks of detraining, and 12 weeks of retraining. Training and retraining were undertaken twice weekly for several upper- and lower-body muscle groups. Skeletal muscle attenuation in Hounsfield units (HU) as well as mid-thigh muscle volume was obtained for the quadriceps and hamstrings. Muscle strength was assessed by 1-repetition maximum and physical function by a battery of tests., Results: The average change in muscle strength following training, detraining and retraining was 48.8+/-2.9%, -17.6+/-1.3%, and 19.8+/-2.0%, respectively. Strength changes were accompanied by significant alterations in muscle density (p<0.001), with the quadriceps HU decreasing by 7.7+/-1.0% following detraining and increasing by 5.4+/-0.5% with retraining. For the hamstrings HU measure, detraining and retraining resulted in an 11.9+/-1.4% loss and a 5.5+/-1.8% gain, respectively. There was no significant change in muscle volume., Conclusion: Cessation of resistance exercise in trained older persons increases the fatty infiltration of muscle, while resumption of exercise decreases it. Monitoring changes in both muscle size and fat infiltration may enable a more comprehensive assessment of exercise in combating age-related muscular changes., (Copyright 2008 S. Karger AG, Basel.)

Introduction: It is important to identify possible pathological mechanisms that underlie the known sexual dimorphism in bone fragility in old age. In this cross-sectional population-based study, we use data from three different skeletal sites to examine sex differences in volumetric bone density, geometry and strength indices and determine whether sex differences in these bone strength measures continue to increase into very old age., Materials and Methods: A total of 1715 elderly individuals (807 men and 908 women) age 67-93 years, participants in a population-based study, the Age, Gene/Environment Susceptibility-Reykjavik Study (AGES-REYKJAVIK) and not taking medications affecting bone metabolism, were studied. Quantitative computed tomography (QCT) was performed in the lumbar spine, hip and mid-femoral shaft to estimate volumetric trabecular, cortical and integral BMD, bone geometry and bone strength indices. Regression models were used to assess the effects of age and gender-adjustment for standing midlife height and current weight., Results: At age 67-69 years, men had 24.9-31.7% larger cross-sectional bone size at measured sites than women. At all bone sites, women had two- to fivefold diminution in net bone mass with age compared to men but had comparable increments in bone size (1.8-6.0% per 10 years). This was reflected in significantly worse (more than twofold) bone strength measures with age in women, including compressive strength indices at the spine, femoral neck and trochanter and bending strength indices at the femoral neck., Conclusion: With the limitations of a cross-sectional study, our data support the hypothesis that sex differences in bone strength continue into old age. These sex differences appear to be due to greater net bone loss in women rather than due to greater bone gain in men.

ObjectiveThis study aimed to investigate how skeletal muscle attenuation and adipose tissue (AT) attenuation of the quadriceps, hamstrings, paraspinal muscle groups and the psoas muscle vary according to the targeted muscles, sex, and age.DesignPopulation-based cross-sectional study.SettingCommunity-dwelling old population in Reykjavik, Iceland.SubjectsA total of 5331 older adults (42.8% women), aged 66-96 years from the Age, Gene/Environment Susceptibility (AGES)- Reykjavik Study, who participated in the baseline visit (between 2002 and 2006) and had valid thigh and abdominal computed tomography (CT) scans were studied.MethodsMuscle attenuation and AT attenuation of the quadriceps, hamstrings, paraspinal muscle groups and the psoas muscle were determined using CT. Linear mixed model analysis of variance was performed for each sex, with skeletal muscle or AT attenuation as the dependent variable.ResultsMuscle attenuation decreased, and AT attenuation increased with age in both sexes, and these differences were specific for each muscle, although not in all age groups. Age-related differences in muscle and AT attenuation varied with specific muscle. In general, for both sexes, skeletal muscle attenuation of the hamstrings declined more than average with age. Men and women displayed a different pattern in the age differences in AT attenuation for each muscle.ConclusionsOur data support the hypotheses that skeletal muscle attenuation decreases, and AT attenuation increases with aging. In addition, our data add new evidence, supporting that age-related differences in skeletal muscle and AT attenuation vary between muscles.

IntroductionIn addition to well-established links with cardiovascular and respiratory diseases, cigarette smoking may affect skeletal muscle; however, associations with quadriceps atrophy, density, and function are unknown. This study explored the associations of current and former smoking with quadriceps muscle area and attenuation as well as muscle force (assessed as knee extension peak torque) and rate of torque development-a measure of muscle power in older adults.MethodsData from 4469 older adults, aged 66-95 years at baseline in the Age, Gene/Environment Susceptibility-Reykjavik Study with measurements of thigh computed tomography, isometric knee extension testing, self-reported smoking history, and potential covariates were analyzed.ResultsSex differences were observed in these data; therefore, our final analyses are stratified by sex. In men, both former smokers and current smokers had lower muscle area (with β= -0.10, 95% confidence interval [CI] = -0.17 to -0.03 and β = -0.19, 95% CI = -0.33 to -0.05, respectively) and lower muscle attenuation (ie, higher fat infiltration, β = -0.08, 95% CI = -0.16 to -0.01 and β = -0.17, 95% CI = -0.34 to -0.01, respectively) when compared with never smokers. Smoking status was not associated with male peak torque or rate of torque development. In women, current smoking was associated with lower muscle attenuation (β = -0.24, 95% CI = -0.34 to -0.13) compared to never smoking. Among female smokers (current and former), muscle attenuation and peak torque were lower with increasing pack-years.ConclusionsResults suggest that cigarette smoking is related to multiple muscle properties at older age and that these relationships may be different among men and women.ImplicationsThis article presents novel data, as it examined for the first time the relationship between smoking and computed tomography-derived quadriceps muscle size (cross-sectional area) and attenuation. This study suggests that current cigarette smoking is related to higher muscle fat infiltration, which may have significant health implications for the older population, because of its known association with poor physical function, falls, and hip fractures.

Bone marrow adiposity (BMA) is associated with aging and osteoporosis, but whether BMA can predict bone loss and fractures remains unknown. Using data from the Age Gene/Environment Susceptibility (AGES)-Reykjavik study, we investigated the associations between 1 H-MRS-based measures of vertebral bone marrow adipose tissue (BMAT), annualized change in bone density/strength by quantitative computed tomography (QCT) and DXA, and secondarily, with incident clinical fractures and radiographic vertebral fractures among older adults. The associations between BMAT and annualized change in bone density/strength were evaluated using linear regression models, adjusted for age, body mass index (BMI), diabetes, estradiol, and testosterone. Cox proportional hazards models were used to evaluate the associations between baseline BMAT and incident clinical fractures, and logistic regression models for incident vertebral fractures. At baseline, mean ± SD age was 80.9 ± 4.2 and 82.6 ± 4.2 years in women (n = 148) and men (n = 150), respectively. Mean baseline BMAT was 55.4% ± 8.1% in women and 54.1% ± 8.2% in men. Incident clinical fractures occurred in 7.4% of women over 2.8 years and in 6.0% of men over 2.2 years. Incident vertebral fractures occurred in 12% of women over 3.3 years and in 17% of men over 2.7 years. Each 1 SD increase in baseline BMAT was associated with a 3.9 mg2 /cm4 /year greater loss of spine compressive strength index (p value = .003), a 0.9 mg/cm3 /year greater loss of spine trabecular BMD (p value = .02), and a 1.2 mg/cm3 /year greater loss of femoral neck trabecular BMD (p value = .02) in women. Among men, there were no associations between BMAT and changes in bone density/strength. There were no associations between BMAT and incident fractures in women or men. In conclusion, we found greater BMAT is associated with greater loss of trabecular bone at the spine and femoral neck, and greater loss of spine compressive strength, in older women. © 2019 American Society for Bone and Mineral Research.

Concerns raised at a 2010 Bone Summit held for National Aeronautics and Space Administration Johnson Space Center led experts in finite element (FE) modeling for hip fracture prediction to propose including hip load capacity in the standards for astronaut skeletal health. The current standards for bone are based upon areal bone mineral density (aBMD) measurements by dual X-ray absorptiometry (DXA) and an adaptation of aBMD cut-points for fragility fractures. Task Group members recommended (i) a minimum permissible outcome limit (POL) for post-mission hip bone load capacity, (ii) use of FE hip load capacity to further screen applicants to astronaut corps, (iii) a minimum pre-flight standard for a second long-duration mission, and (iv) a method for assessing which post-mission physical activities might increase an astronaut's risk for fracture after return. QCT-FE models of eight astronaut were analyzed using nonlinear single-limb stance (NLS) and posterolateral fall (NLF) loading configurations. QCT data from the Age Gene/Environment Susceptibility (AGES) Reykjavik cohort and the Rochester Epidemiology Project were analyzed using identical modeling procedures. The 75th percentile of NLS hip load capacity for fractured elderly males of the AGES cohort (9537N) was selected as a post-mission POL. The NLF model, in combination with a Probabilistic Risk Assessment tool, was used to assess the likelihood of exceeding the hip load capacity during post-flight activities. There was no recommendation to replace the current DXA-based standards. However, FE estimation of hip load capacity appeared more meaningful for younger, physically active astronauts and was recommended to supplement aBMD cut-points.

Bone marrow adiposity is associated with aging, osteoporosis, and reduced hematopoiesis, as well as anorexia nervosa, but little is known about the underlying mechanisms that affect marrow adiposity. Chronic kidney disease (CKD) may influence bone marrow adipose tissue (BMAT), possibly through loss of lean mass or higher circulating levels of sclerostin. To test these hypotheses, we investigated the cross-sectional association between estimated glomerular filtration rate (eGFR) as a measure of kidney function and 1 H-MRS-based measurement of vertebral BMAT (L1 to L4) in 475 older adults from the Age Gene/Environment Susceptibility (AGES)-Reykjavik study. Mean BMAT was compared in those with eGFR >60 (n = 297) versus those with eGFR 45 to 60 (n = 120) or eGFR 60 (adjusted mean 53.8%; 95% CI, 52.8 to 54.8) (p = 0.0002). BMAT did not differ in those with eGFR 45 to 60 (adjusted mean 54.3%; 95% CI, 52.8 to 55.9) compared with those with eGFR >60 (p = 0.58). In a subgroup of participants with serum sclerostin available (n = 253), additional adjustment for sclerostin attenuated the difference in adjusted mean vertebral BMAT between those with eGFR 60 from 3.7% (p = 0.04) to 2.4% (p = 0.20). CKD stage 3b or worse was associated with greater bone marrow adiposity; this association may be partially mediated by sclerostin. © 2018 American Society for Bone and Mineral Research.

In this case-cohort study, we used data-driven computational anatomy approaches to assess within and between sex spatial differences in proximal femoral bone characteristics in relation to incident hip fracture. One hundred male and 234 female incident hip fracture cases, and 1047 randomly selected noncase subcohort participants (562 female) were chosen from the population-based AGES-Reykjavik study (mean age of 77 years). The baseline -i.e. before hip fracture- hip quantitative computed tomography scans of these subjects were analyzed using voxel-based morphometry, tensor-based morphometry, and surface-based statistical parametric mapping to assess the spatial distribution of volumetric bone mineral density (vBMD), internal structure, and cortical bone properties (thickness, vBMD and trabecular vBMD adjacent to the endosteal surface) of the proximal femur, respectively, in relation to incident hip fracture. Results showed that in both men and women: 1) the superior aspect of the femoral neck and the trochanteric region (except for cortical bone thickness) were consistently identified as being associated with incident hip fracture, and 2) differences in bone properties between noncases and incident hip fracture cases followed similar trends, were located at compatible regions, and manifested heterogeneity in the spatial distribution of their magnitude with focal regions showing larger differences. With respect to sex differences, most of the regions with a significant interaction between fracture group and sex showed: 1) differences of greater magnitude in men between noncases and incident hip fracture cases with different spatial distributions for all bone properties with the exception of cortical bone thickness, and 2) that while most of these regions showed better bone quality in male cases than in female cases, female cases showed higher vBMD in the principal compressive group and higher endotrabecular vBMD at several regions including the anterior, posterior, and lateral aspects of the proximal femur. These findings indicate the value of these image analysis techniques by providing unique information about the specific patterns of bone deterioration associated with incident hip fracture and their sex differences, highlighting the importance of looking to men and women separately in the assessment of hip fracture risk.

This study aimed to explore the relationships of several indicators of cigarette smoking habits (smoking status, pack-years, age at smoking initiation and smoking cessation) with quantitative computed tomographic (QCT)-derived proximal femur bone measures (trabecular vBMD, integral vBMD and the ratio of cortical to total tissue volume (cvol/ivol)) and with subsequent change in these measures over the next five years. A total of 2673 older adults (55.9% women), aged 66-92 years at baseline from the Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study, who had two QCT scans of the hip were studied. In multivariable linear regression models, compared to never-smokers, current smokers had lower cvol/ivol at baseline and former-smokers had poorer measures on all outcomes (lower trabecular vBMD, integral vBMD and cvol/ivol), even when adjusted for several potential confounders. Further, among former smokers, those with higher pack-years had worse bone outcomes and those with longer duration since smoking cessation had better bone health at baseline. Analyses of change in bone measures revealed that compared to never-smokers, current smokers had significantly greater loss of trabecular vBMD, integral vBMD, and cvol/ivol. The regression models included adjustment for sex, age, education, and baseline body mass index, creatinine, % weight change from age 50, 25OHD, physical activity level, high-sensitive C-Reactive protein levels, alcohol and coffee consumption, history of diabetes mellitus, arthritis, and respiratory diseases. In conclusion, both current and former smoking showed adverse associations with bone health assessed with QCT. Results suggest that current smoking in particular may aggravate the rate of bone loss at older age and highlight implications for targeting this risk factor in populations that present higher smoking prevalence and vulnerability to bone fragility.

ContextHigher bone marrow fat (BMF)1 is associated with osteoporosis and reduced hematopoiesis. Exogenous estradiol reduces BMF in older women, but effects of endogenous sex hormones are unknown.ObjectiveTo determine if endogenous sex hormones are associated with BMF in older men and women.Design, setting and participantsCross-sectional study in the Age Gene/Environment Susceptibility (AGES) Reykjavik cohort. Participants using medications that may affect BMF were excluded.Main outcome measuresVertebral BMF was measured with magnetic resonance spectroscopy. Estradiol, testosterone and sex hormone binding globulin were measured on archived serum. Linear regression models were adjusted for age, total percent body fat and visit window.ResultsAnalyses included 244 men and 226 women, mean age 81.5 (SD 4.1) years. Mean BMF was 54.1% (SD 8.6) (men) and 54.7% (SD 8.1) (women). In adjusted models, per 1pg/ml increase in total estradiol, there was a statistically significant 0.26% decrease in BMF in men (95% CI: -0.41, -0.11) and a non-significant 0.20% decrease in women (95% CI: -0.55, 0.15), with no evidence of interaction by gender (p=0.88). Per 10ng/dl increase in total testosterone, there was a significant 0.10% decrease in BMF in men (95% CI: -0.17, -0.03) and a non-significant 0.13% (95% CI: -0.79, 0.53) decrease in women, with no evidence of interaction by gender (p=0.97).ConclusionHigher bone marrow fat is associated with lower total estradiol and testosterone levels in older men, with a similar but statistically non-significant association in older women. Sex hormone levels appear to play a role in the regulation of bone marrow fat in older adults.

BackgroundAlthough the importance of sleep on preservation of several physiological functions is well known, the relationship with the two interconnected tissues - muscle and bone is less understood.ObjectivesThis study aimed to examine the association of 24-hour sleep duration with mid-thigh muscle composition and proximal femur volumetric bone mineral density (vBMD).Methods2438 men and 3326 women aged 66 to 96years, residents in the Reykjavik area, were included in this cross-sectional study. Proximal femur integral vBMD, mid-thigh muscle area and muscle attenuation were assessed with computed tomography. Sleep and nap habits were assessed using a questionnaire.ResultsWe found that after adjustment for age and BMI long sleep duration (>8h/d) was negatively associated with thigh lean area in both men (B=-2.21, 95% confidence interval (CI): -4.01, -0.40) and women (B=-2.39, 95% CI: -3.75, -1.03) and with muscle attenuation (B=-0.95, 95% CI: -1.47, -0.43) only in women. After adjustments for age, health and lifestyle factors the association between long sleep duration and muscle lean area was attenuated and became nonsignificant while associations with muscle attenuation remained marginally significant (B=-0.51, 95% CI: -1.03, -0.002). Sleep duration was not associated with proximal femur integral vBMD in the multivariate models.ConclusionLong sleep duration, particularly in old women, can affect thigh muscle attenuation (increase in intramuscular fat). Whether optimization of sleep can ameliorate age-associated intramuscular or intermuscular adipose tissue warrants further studies.

Bone mineral density (BMD) has been linked to mortality, but little is known about the independent contribution of each endosteal bone compartment and also the rate of bone loss to risk of mortality. We examined the relationships between (1) baseline trabecular and cortical volumetric BMD (vBMD) at the proximal femur, and (2) the rate of trabecular and cortical bone loss and all-cause mortality in older adults from the AGES-Reykjavik study. The analysis of trabecular and cortical vBMD and mortality was based on the baseline cohort of 4654 participants (aged ≥66 years) with a median follow-up of 9.4 years; the association between rate of bone loss and mortality was based on 2653 participants with bone loss data (median follow-up of 5.6 years). Analyses employed multivariable Cox-proportional models to estimate hazard ratios (HRs) with time-varying fracture status; trabecular and cortical variables were included together in all models. Adjusted for important confounders, Cox models showed that participants in the lowest quartile of trabecular vBMD had an increased risk of mortality compared to participants in other quartiles (HR = 1.12; 95% confidence interval (CI), 1.01 to 1.25); baseline cortical vBMD was not related to mortality (HR = 1.08; 95% CI, 0.97 to 1.20). After adjustment for time-dependent fracture status, results were attenuated and not statistically significant. A faster loss (quartile 1 versus quartiles 2-4) in both trabecular and cortical bone was associated with higher mortality risk (HR = 1.37 and 1.33, respectively); these associations were independent of major potential confounders including time-dependent incident fractures (HR = 1.32 and 1.34, respectively). Overall, data suggest that faster bone losses over time in both the trabecular and cortical bone compartments are associated with mortality risk and that measurements of change in bone health may be more informative than single-point measurements in explaining mortality differences in older adults. © 2017 American Society for Bone and Mineral Research.

Without effective countermeasures, the musculoskeletal system is altered by the microgravity environment of long-duration spaceflight, resulting in atrophy of bone and muscle tissue, as well as in deficits in the function of cartilage, tendons, and vertebral disks. While inflight countermeasures implemented on the International Space Station have evidenced reduction of bone and muscle loss on low-Earth orbit missions of several months in length, important knowledge gaps must be addressed in order to develop effective strategies for managing human musculoskeletal health on exploration class missions well beyond Earth orbit. Analog environments, such as bed rest and/or isolation environments, may be employed in conjunction with large sample sizes to understand sex differences in countermeasure effectiveness, as well as interaction of exercise with pharmacologic, nutritional, immune system, sleep and psychological countermeasures. Studies of musculoskeletal biomechanics, involving both human subject and computer simulation studies, are essential to developing strategies to avoid bone fractures or other injuries to connective tissue during exercise and extravehicular activities. Animal models may be employed to understand effects of the space environment that cannot be modeled using human analog studies. These include studies of radiation effects on bone and muscle, unraveling the effects of genetics on bone and muscle loss, and characterizing the process of fracture healing in the mechanically unloaded and immuno-compromised spaceflight environment. In addition to setting the stage for evidence-based management of musculoskeletal health in long-duration space missions, the body of knowledge acquired in the process of addressing this array of scientific problems will lend insight into the understanding of terrestrial health conditions such as age-related osteoporosis and sarcopenia.

UNLABELLED: Association between serum bone formation and resorption markers and cortical and trabecular bone loss and the concurrent periosteal apposition in a population-based cohort of 1069 older adults was assessed. BTM levels moderately reflect the cellular events at the endosteal and periosteal surfaces but are not associated with fracture risk. INTRODUCTION: We assessed whether circulating bone formation and resorption markers (BTM) were individual predictors for trabecular and cortical bone loss, periosteal expansion, and fracture risk in older adults aged 66 to 93 years from the AGES-Reykjavik study. METHODS: The sample for the quantitative computed tomography (QCT)-derived cortical and trabecular BMD and periosteal expansion analysis consisted of 1069 participants (474 men and 595 women) who had complete baseline (2002 to 2006) and follow-up (2007 to 2011) hip QCT scans and serum baseline BTM. During the median follow-up of 11.7 years (range 5.4-12.5), 54 (11.4 %) men and 182 (30.6 %) women sustained at least one fracture of any type. RESULTS: Increase in BTM levels was associated with faster cortical and trabecular bone loss at the femoral neck and proximal femur in men and women. Higher BTM levels were positively related with periosteal expansion rate at the femoral neck in men. Markers were not associated with fracture risk. CONCLUSION: This data corroborates the notion from few previous studies that both envelopes are metabolically active and that BTM levels may moderately reflect the cellular events at the endosteal and periosteal surfaces. However, our results do not support the routine use of BTM to assess fracture risk in older men and women. In light of these findings, further studies are justified to examine whether systemic markers of bone turnover might prove useful in monitoring skeletal remodeling events and the effects of current osteoporosis drugs at the periosteum.

Genome-wide association studies (GWASs) have revealed numerous loci for areal bone mineral density (aBMD). We completed the first GWAS meta-analysis (n = 15,275) of lumbar spine volumetric BMD (vBMD) measured by quantitative computed tomography (QCT), allowing for examination of the trabecular bone compartment. SNPs that were significantly associated with vBMD were also examined in two GWAS meta-analyses to determine associations with morphometric vertebral fracture (n = 21,701) and clinical vertebral fracture (n = 5893). Expression quantitative trait locus (eQTL) analyses of iliac crest biopsies were performed in 84 postmenopausal women, and murine osteoblast expression of genes implicated by eQTL or by proximity to vBMD-associated SNPs was examined. We identified significant vBMD associations with five loci, including: 1p36.12, containing WNT4 and ZBTB40; 8q24, containing TNFRSF11B; and 13q14, containing AKAP11 and TNFSF11. Two loci (5p13 and 1p36.12) also contained associations with radiographic and clinical vertebral fracture, respectively. In 5p13, rs2468531 (minor allele frequency [MAF] = 3%) was associated with higher vBMD (β = 0.22, p = 1.9 × 10-8 ) and decreased risk of radiographic vertebral fracture (odds ratio [OR] = 0.75; false discovery rate [FDR] p = 0.01). In 1p36.12, rs12742784 (MAF = 21%) was associated with higher vBMD (β = 0.09, p = 1.2 × 10-10 ) and decreased risk of clinical vertebral fracture (OR = 0.82; FDR p = 7.4 × 10-4 ). Both SNPs are noncoding and were associated with increased mRNA expression levels in human bone biopsies: rs2468531 with SLC1A3 (β = 0.28, FDR p = 0.01, involved in glutamate signaling and osteogenic response to mechanical loading) and rs12742784 with EPHB2 (β = 0.12, FDR p = 1.7 × 10-3 , functions in bone-related ephrin signaling). Both genes are expressed in murine osteoblasts. This is the first study to link SLC1A3 and EPHB2 to clinically relevant vertebral osteoporosis phenotypes. These results may help elucidate vertebral bone biology and novel approaches to reducing vertebral fracture incidence. © 2016 American Society for Bone and Mineral Research.

Muscle composition may affect mortality risk, but prior studies have been limited to specific samples or less precise determination of muscle composition. We evaluated associations of thigh muscle composition, determined using computed tomography imaging, and knee extension strength with mortality risk among 4,824 participants aged 76.4 (standard deviation (SD), 5.5) years from the Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study (2002-2006). Cox proportional hazards models were used to estimate hazard ratios. After 8.8 years of follow-up, there were 1,942 deaths. For men, each SD-increment increase in muscle lean area, muscle quality, and strength was associated with lower mortality risk, with decreases ranging between 11% and 22%. Each SD-increment increase in intermuscular adipose tissue and intramuscular adipose tissue was associated with higher mortality risk (hazard ratio (HR) = 1.13 (95% confidence interval (CI): 1.06, 1.22) and HR = 1.23 (95% CI: 1.15, 1.30), respectively). For women, each SD-increment increase in muscle lean area, muscle quality, and strength was associated with lower mortality risk, with decreases ranging between 12% and 19%. Greater intramuscular adipose tissue was associated with an 8% higher mortality risk (HR = 1.08, 95% CI: 1.01, 1.16). This study shows that muscle composition is associated with mortality risk. These results also show the importance of improving muscle strength and area and lowering muscle adipose tissue infiltration.

Muscle composition may affect mortality risk, but prior studies have been limited to specific samples or less precise determination of muscle composition. We evaluated associations of thigh muscle composition, determined using computed tomography imaging, and knee extension strength with mortality risk among 4,824 participants aged 76.4 (standard deviation (SD), 5.5) years from the Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study (2002-2006). Cox proportional hazards models were used to estimate hazard ratios. After 8.8 years of follow-up, there were 1,942 deaths. For men, each SD-increment increase in muscle lean area, muscle quality, and strength was associated with lower mortality risk, with decreases ranging between 11% and 22%. Each SD-increment increase in intermuscular adipose tissue and intramuscular adipose tissue was associated with higher mortality risk (hazard ratio (HR) = 1.13 (95% confidence interval (CI): 1.06, 1.22) and HR = 1.23 (95% CI: 1.15, 1.30), respectively). For women, each SD-increment increase in muscle lean area, muscle quality, and strength was associated with lower mortality risk, with decreases ranging between 12% and 19%. Greater intramuscular adipose tissue was associated with an 8% higher mortality risk (HR = 1.08, 95% CI: 1.01, 1.16). This study shows that muscle composition is associated with mortality risk. These results also show the importance of improving muscle strength and area and lowering muscle adipose tissue infiltration.

BackgroundQuantitative computed tomography (QCT) imaging is the basis for multiple assessments of bone quality in the proximal femur, including volumetric bone mineral density (vBMD), tissue volume, estimation of bone strength using finite element modeling (FEM), cortical bone thickness, and computational-anatomy-based morphometry assessments.MethodsHere, we present an automatic framework to perform a multi-parametric QCT quantification of the proximal femur. In this framework, the proximal femur is cropped from the bilateral hip scans, segmented using a multi-atlas based segmentation approach, and then assigned volumes of interest through the registration of a proximal femoral template. The proximal femur is then subjected to compartmental vBMD, compartmental tissue volume, FEM bone strength, compartmental surface-based cortical bone thickness, compartmental surface-based vBMD, local surface-based cortical bone thickness, and local surface-based cortical vBMD computations. Consequently, the template registrations together with vBMD and surface-based cortical bone parametric maps enable computational anatomy studies. The accuracy of the segmentation was validated against manual segmentations of 80 scans from two clinical facilities, while the multi-parametric reproducibility was evaluated using repeat scans with repositioning from 22 subjects obtained on CT imaging systems from two manufacturers.ResultsAccuracy results yielded a mean dice similarity coefficient of 0.976±0.006, and a modified Haussdorf distance of 0.219±0.071 mm. Reproducibility of QCT-derived parameters yielded root mean square coefficients of variation (CVRMS) between 0.89-1.66% for compartmental vBMD; 0.20-1.82% for compartmental tissue volume; 3.51-3.59% for FEM bone strength; 1.89-2.69% for compartmental surface-based cortical bone thickness; and 1.08-2.19% for compartmental surface-based cortical vBMD. For local surface-based assessments, mean CVRMS were between 3.45-3.91% and 2.74-3.15% for cortical bone thickness and vBMD, respectively.ConclusionsThe automatic framework presented here enables accurate and reproducible QCT multi-parametric analyses of the proximal femur. Our subjects were elderly, with scans obtained across multiple clinical sites and manufacturers, thus documenting its value for clinical trials and other multi-site studies.

Nonpharmacologic approaches to preserve or increase bone mineral density (BMD) include whole-body vibration (WBV), but its efficacy in elderly persons is not clear. Therefore, we conducted the Vibration to Improve Bone in Elderly Subjects (VIBES) trial, a randomized, placebo-controlled trial of 10 minutes of daily WBV (0.3g at 37 Hz) in seniors recruited from 16 independent living communities. The primary outcomes were volumetric BMD of the hip and spine measured by quantitative computed tomography (QCT) and biochemical markers of bone turnover. We randomized 174 men and women (89 active, 85 placebo) with T-scores -1 to -2.5 who were not taking bone active drugs and had no diseases affecting the skeleton (mean age 82 ± 7 years, range 65 to 102). Participants received daily calcium (1000 mg) and vitamin D (800 IU). Study platforms were activated using radio frequency ID cards providing electronic adherence monitoring; placebo platforms resembled the active platforms. In total, 61% of participants in the active arm and 73% in the placebo arm completed 24 months. The primary outcomes, median percent changes (interquartile range [IQR]) in total volumetric femoral trabecular BMD (active group (2.2% [-0.8%, 5.2%]) versus placebo 0.4% [-4.8%, 5.0%]) and in mid-vertebral trabecular BMD of L1 and L2 (active group (5.3% [-6.9%, 13.3%]) versus placebo (2.4% [-4.4%, 11.1%]), did not differ between groups (all p values > 0.1). Changes in biochemical markers of bone turnover (P1NP and sCTX) also were not different between groups (p = 0.19 and p = 0.97, respectively). In conclusion, this placebo-controlled randomized trial of daily WBV in older adults did not demonstrate evidence of significant beneficial effects on volumetric BMD or bone biomarkers; however, the high variability in vBMD changes limited our power to detect small treatment effects. The beneficial effects of WBV observed in previous studies of younger women may not occur to the same extent in elderly individuals.

BackgroundPolyunsaturated fatty acids (PUFAs) may play a role in fracture, but studies have been largely confined to estimates of dietary intake.ObjectiveWe aimed to examine associations between fatty acids measured in late life and fish-oil consumption in early life, midlife, and late life with osteoporotic fracture risk.DesignOsteoporotic fractures were determined from medical records over 5-9 y of follow-up in men and women aged 66-96 y. Data were analyzed from 1438 participants including 898 participants who were randomly selected from the Age, Gene/Environment Susceptibility Study, which is an observational study, and 540 participants with incident fracture. Plasma phospholipid fatty acids were assessed by using gas chromatography. Fish-oil consumption was assessed by using validated questionnaires as never (referent), less than daily, or daily. HRs and 95% CIs adjusted for age, education, height, weight, diabetes, physical activity, and medications were estimated by using Cox regression.ResultsIn men, the highest tertile of PUFAs, n-3 (ω-3), and eicosapentaenoic acid were associated with decreased fracture risk [HRs (95% CIs): 0.60 (95% CI: 0.41, 0.89), 0.66 (0.45, 0.95), and 0.59 (0.41, 0.86), respectively]. In women, PUFAs tended to be inversely associated with fracture risk (P-trend = 0.06), but tertiles 2 and 3 were not independently associated with risk. Tertile 2 of n-6 and arachidonic acid was associated with fracture risk in women [HRs (95% CIs): 1.43 (1.10, 1.85) and 1.42 (1.09, 1.85), respectively]. Daily fish-oil consumption in late life was associated with lower fracture risk in men (HR: 0.64; 95% CI: 0.45, 0.91). Daily fish-oil consumption in midlife was associated with lower fracture risk in women (HR: 0.75; 95% CI: 0.58, 0.98).ConclusionsGreater PUFA concentrations may be associated with lower osteoporotic fracture risk in older adults, particularly in men. Critical time periods for n-3 fatty acid consumption may differ by sex.

ContextOsteocyte activity is crucial to the maintenance of bone quality. Sclerostin, an osteocyte product, inhibits bone formation, yet higher circulating sclerostin is associated with higher bone density. Bone marrow fat (MF) is associated with osteoporosis, but little is known about the relationship between osteocyte activity and MF.ObjectiveOur objective was to assess the relationships between circulating sclerostin, vertebral MF, volumetric bone mineral density (vBMD), and other fat depots in older adults.Design, setting, and participantsWe conducted a cross-sectional study in the Age Gene/Environment Susceptibility-Reykjavik cohort.Main outcome measuresOutcome measures included vertebral MF (L1-L4) measured with magnetic resonance spectroscopy and vBMD (spine and hip) and abdominal fat measured with quantitative computed tomography.ResultsAfter excluding subjects with bone-active medication use (n = 50), inadequate serum (n = 2), or inadequate magnetic resonance spectroscopy (n = 1), analyses included 115 men and 134 women (mean age 79 y, mean body mass index 27.7 kg/m(2)). In men, but not women, vertebral MF was greater in those with higher serum sclerostin levels. MF was 52.2 % in the lowest tertile of serum sclerostin and 56.3% in the highest tertile in men (P for trend

Bone mineral density (BMD) and geometric bone measures are individually associated with prevalent osteoporotic fractures. Whether an aggregate of these measures would better associate with fractures has not been examined. We examined relationships between self-reported fractures and selected bone measures acquired by quantitative computerized tomography (QCT), a composite bone score, and QCT-acquired dual-energy X-ray absorptiometry-like total femur BMD in 2110 men and 2682 women in the Age, Gene/Environment Susceptibility-Reykjavik Study. The combined bone score was generated by summing gender-specific Z-scores for 4 QCT measures: vertebral trabecular BMD, femur neck cortical thickness, femur neck trabecular BMD, and femur neck minimal cross-sectional area. Except for the latter measure, lower scores for QCT measures, singly and combined, showed positive (p

Fractures of the proximal femur are the most devastating outcome of osteoporosis. It is generally understood that age-related changes in hip structure confer increased risk, but there have been few explicit comparisons of such changes in healthy subjects to those with hip fracture. In this study, we used quantitative computed tomography and tensor-based morphometry (TBM) to identify three-dimensional internal structural patterns of the proximal femur associated with age and with incident hip fracture. A population-based cohort of 349 women representing a broad age range (21-97years) was included in this study, along with a cohort of 222 older women (mean age 79±7years) with (n=74) and without (n=148) incident hip fracture. Images were spatially normalized to a standardized space, and age- and fracture-specific morphometric features were identified based on statistical maps of shape features described as local changes of bone volume. Morphometric features were visualized as maps of local contractions and expansions, and significance was displayed as Student's t-test statistical maps. Significant age-related changes included local expansions of regions low in volumetric bone mineral density (vBMD) and local contractions of regions high in vBMD. Some significant fracture-related features resembled an accentuated aging process, including local expansion of the superior aspect of the trabecular bone compartment in the femoral neck, with contraction of the adjoining cortical bone. However, other features were observed only in the comparison of hip fracture subjects with age-matched controls including focal contractions of the cortical bone at the superior aspect of the femoral neck, the lateral cortical bone just inferior to the greater trochanter, and the anterior intertrochanteric region. Results of this study support the idea that the spatial distribution of morphometric features is relevant to age-related changes in bone and independent to fracture risk. In women, the identification by TBM of fracture-specific morphometric alterations of the proximal femur, in conjunction with vBMD and clinical risk factors, may improve hip fracture prediction.

ContextBone marrow fat (BMF) and bone mineral density (BMD) by dual x-ray energy absorptiometry (DXA) are negatively correlated. However, little is known about the association of BMF with fracture or with separate trabecular and cortical bone compartments.ObjectiveOur objective was to assess the relationships between vertebral BMF, BMD by quantitative computed tomography, and fracture in older adults.Design, setting, and participantsWe conducted a cross-sectional study in the Age Gene/Environment Susceptibility-Reykjavik cohort.Main outcome measuresOutcomes measures included vertebral BMF (L1-L4) measured with magnetic resonance spectroscopy, quantitative computed tomography and DXA scans of the hip and spine, and DXA vertebral fracture assessments. Previous clinical fracture was determined from medical records.ResultsIn 257 participants without recent bone-active medication use, mean age was 79 (SD 3.1) years. Mean BMF was 53.5% ± 8.1% in men and 55.0% ± 8.4% in women. Those with prevalent vertebral fracture (21 men, 32 women) had higher mean BMF in models adjusted for BMD. In separate models by sex, the difference was statistically significant only in men (57.3% vs 52.8%, P = 0.02). BMF was associated with lower trabecular volumetric BMD (vBMD) at the spine (-10.5% difference for each 1 SD increase in BMF, P < 0.01), total hip, and femoral neck, but not with cortical vBMD, in women. In men, BMF was marginally associated with trabecular spine vBMD (-6.1%, P = 0.05). Total hip and spine areal BMD (aBMD) were negatively correlated with BMF in women only.ConclusionHigher marrow fat correlated with lower trabecular, but not cortical, BMD in older women but not men. Higher marrow fat was associated with prevalent vertebral fracture in men, even after adjustment for BMD.

Hip fracture risk rises exponentially with age, but there is little knowledge about how fracture-related alterations in hip structure differ from those of aging. We employed computed tomography (CT) imaging to visualize the three-dimensional (3D) spatial distribution of bone mineral density (BMD) in the hip in relation to age and incident hip fracture. We used intersubject image registration to integrate 3D hip CT images into a statistical atlas comprising women aged 21 to 97 years (n = 349) and a group of women with (n = 74) and without (n = 148) incident hip fracture 4 to 7 years after their imaging session. Voxel-based morphometry was used to generate Student's t test statistical maps from the atlas, which indicated regions that were significantly associated with age or with incident hip fracture. Scaling factors derived from intersubject image registration were employed as measures of bone size. BMD comparisons of young, middle-aged, and older American women showed preservation of load-bearing cortical and trabecular structures with aging, whereas extensive bone loss was observed in other trabecular and cortical regions. In contrast, comparisons of older Icelandic fracture women with age-matched controls showed that hip fracture was associated with a global cortical bone deficit, including both the superior cortical margin and the load-bearing inferior cortex. Bone size comparisons showed larger dimensions in older compared to younger American women and in older Icelandic fracture women compared to controls. The results indicate that older Icelandic women who sustain incident hip fracture have a structural phenotype that cannot be described as an accelerated pattern of normal age-related loss. The fracture-related cortical deficit noted in this study may provide a biomarker of increased hip fracture risk that may be translatable to dual-energy X-ray absorptiometry (DXA) and other clinical images.

ContextIdiopathic osteoporosis (IOP) affects otherwise healthy young individuals with intact gonadal function and no secondary cause of bone fragility. In premenopausal women with IOP, a low trauma fracture is evidence of impaired bone quality and strength. The extent to which low bone mineral density (BMD) by dual-energy x-ray absorptiometry (DXA) reflects low volumetric BMD, bone microstructure, and strength is uncertain in the absence of low trauma fracture.ObjectiveThe objective of the study was to compare three-dimensional volumetric BMD and bone stiffness in premenopausal women with IOP based on fracture history, those with idiopathic low BMD (Z score ≤ -2.0) and no low trauma fracture, and normal age-matched controls.DesignWe measured volumetric BMD and bone geometry by central quantitative computed tomography (cQCT) scans of the spine and hip and estimated bone stiffness by finite element analysis of cQCT data sets in 32 premenopausal women with IOP, 12 with idiopathic low BMD, and 34 controls.ResultsSubjects had comparable decreases in total and trabecular volumetric BMD, cortical thickness, and whole-bone stiffness compared with controls, regardless of fracture history. These differences remained significant after controlling for age, body mass index, and bone size. The positive predictive values of a DXA Z score of -2.0 or less for a cQCT volumetric BMD Z score of -2.0 or less were 95% at the lumbar spine, 90% at the total hip, and 86% at the femoral neck.ConclusionWomen with idiopathic low BMD alone and those with low trauma fractures had comparable deficits in bone mass, structure, and stiffness. Low areal BMD by DXA is fairly accurate for predicting low volumetric BMD by cQCT. These results are consistent with three-dimensional bone imaging at the iliac crest, radius, and tibia in premenopausal IOP and suggest that the term osteoporosis may be appropriate in women with Z scores below -2.0, whether or not there is a history of fracture.

Muscle forces are a strong determinant of bone structure, particularly during the process of growth and development. The gender divergence in the bone-muscle relationship becomes strongly evident during adolescence. In females, growth is characterized by increased estrogen levels and increased mass and strength of bone relative to that of muscle, whereas in men, increases in testosterone fuel large increases in muscle, resulting in muscle forces that coincide with a large growth in bone dimensions and strength. In adulthood, significant age-related losses are observed for both bone and muscle tissues. Large decrease in estrogen levels in women appears to diminish the skeleton's responsiveness to exercise more than in men. In contrast, the aging of the muscle-bone axis in men is a function of age related declines in both hormones. In addition to the well-known age related changes in the mechanical loading of bone by muscle, newer studies appear to provide evidence of age- and gender-related variations in molecular signaling between bone and muscle that are independent of purely mechanical interactions. In summary, gender differences in the acquisition and age-related loss in bone and muscle tissues may be important for developing gender-specific strategies for using exercise to reduce bone loss with aging.

Fatty infiltration of muscle, myosteatosis, increases with age and results in reduced muscle strength and function and increased fall risk. However, it is unknown if increased fatty infiltration of muscle predisposes to hip fracture. We measured the mean Hounsfield unit (HU) of the lean tissue within the midthigh muscle bundle (thigh muscle HU, an indicator of intramuscular fat), its cross-sectional area (CSA, a measure of muscle mass) by computed tomography (CT), bone mineral density (BMD) of the hip and total-body percent fat by dual X-ray absorptiometry (DXA), isokinetic leg extensor strength, and the Short Physical Performance Battery (SPPB) in 2941 white and black women and men aged 70 to 79 years. Sixty-three hip fractures were validated during 6.6 years of follow-up. Proportional hazards regression analysis was used to assess the relative risk (RR) of hip fracture across variations in thigh muscle attenuation, CSA, muscle strength, and physical function for hip fracture. In models adjusted by age, race, gender, body mass index, and percentage fat, decreased thigh muscle HU resulted in increased risk of hip fracture [RR/SD = 1.58; 95% confidence interval (CI) 1.10-1.99], an association that continued to be significant after further adjustment for BMD. In models additionally adjusted by CSA, muscle strength, and SPPB score, decreased thigh muscle HU but none of the other muscle parameters continued to be associated with an increased risk of hip fracture (RR/SD = 1.42; 95% CI 1.03-1.97). Decreased thigh muscle HU, a measure of fatty infiltration of muscle, is associated with increased risk of hip fracture and appears to account for the association between reduced muscle strength, physical performance, and muscle mass and risk of hip fracture. This characteristic captures a physical characteristic of muscle tissue that may have importance in hip fracture etiology.

In contrast to conventional dual-energy X-ray absorptiometry, quantitative computed tomography separately measures trabecular and cortical volumetric bone mineral density (vBMD). Little is known about the genetic variants associated with trabecular and cortical vBMD in humans, although both may be important for determining bone strength and osteoporotic risk. In the current analysis, we tested the hypothesis that there are genetic variants associated with trabecular and cortical vBMD at the femoral neck by genotyping 4608 tagging and potentially functional single-nucleotide polymorphisms (SNPs) in 383 bone metabolism candidate genes in 822 Caucasian men aged 65 years or older from the Osteoporotic Fractures in Men Study (MrOS). Promising SNP associations then were tested for replication in an additional 1155 men from the same study. We identified SNPs in five genes (IFNAR2, NFATC1, SMAD1, HOXA, and KLF10) that were robustly associated with cortical vBMD and SNPs in nine genes (APC, ATF2, BMP3, BMP7, FGF18, FLT1, TGFB3, THRB, and RUNX1) that were robustly associated with trabecular vBMD. There was no overlap between genes associated with cortical vBMD and trabecular vBMD. These findings identify novel genetic variants for cortical and trabecular vBMD and raise the possibility that some genetic loci may be unique for each bone compartment.

FSH may have independent actions on bone remodeling and body fat regulation. Cross-sectionally, we have shown that serum FSH is associated with bone mineral density (BMD) and body fat in older postmenopausal women, but it remains unknown whether FSH predicts bone and fat changes. Objective: We examined whether baseline FSH level is associated with subsequent bone loss or body composition changes in older adults. Setting, Design, Participants: We studied 162 women and 158 men (mean age 82 ± 4 years) from the Age, Gene/Environment Susceptibility (AGES)-Bone Marrow Adiposity cohort, a substudy of the AGES-Reykjavik Study of community-dwelling older adults. Skeletal health and body composition were characterized at baseline and 3 years later. Main Outcomes: Annualized change in BMD and body composition by dual-energy X-ray absorptiometry (DXA) and quantitative computed tomography (QCT). Models were adjusted for serum estradiol and testosterone levels. Results: There was no evidence for an association between baseline FSH level and change in BMD or body composition by DXA or QCT. For femoral neck areal BMD, adjusted mean difference (95% CI) per SD increase in FSH was 1.3 (-0.7 to 3.3) mg/cm2/y in women, and -0.2 (-2.6 to 2.2) mg/cm2/y in men. For visceral fat, adjusted mean difference (95% CI) per SD increase in FSH was 1.80 (-0.03 to 3.62) cm2/y in women, and -0.33 (-3.73 to 3.06) cm2/y in men. Conclusions: Although cross-sectional studies and studies in perimenopausal women have demonstrated associations between FSH and BMD and body composition, in older adults, FSH level is not associated with bone mass or body composition changes. [ABSTRACT FROM AUTHOR]

This study aimed to explore the relationships of several indicators of cigarette smoking habits (smoking status, pack-years, age at smoking initiation and smoking cessation) with quantitative computed tomographic (QCT)-derived proximal femur bone measures (trabecular vBMD, integral vBMD and the ratio of cortical to total tissue volume (cvol/ivol)) and with subsequent change in these measures over the next five years. A total of 2673 older adults (55.9% women), aged 66–92 years at baseline from the Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study, who had two QCT scans of the hip were studied. In multivariable linear regression models, compared to never-smokers, current smokers had lower cvol/ivol at baseline and former-smokers had poorer measures on all outcomes (lower trabecular vBMD, integral vBMD and cvol/ivol), even when adjusted for several potential confounders. Further, among former smokers, those with higher pack-years had worse bone outcomes and those with longer duration since smoking cessation had better bone health at baseline. Analyses of change in bone measures revealed that compared to never-smokers, current smokers had significantly greater loss of trabecular vBMD, integral vBMD, and cvol/ivol. The regression models included adjustment for sex, age, education, and baseline body mass index, creatinine, % weight change from age 50, 25OHD, physical activity level, high-sensitive C-Reactive protein levels, alcohol and coffee consumption, history of diabetes mellitus, arthritis, and respiratory diseases. In conclusion, both current and former smoking showed adverse associations with bone health assessed with QCT. Results suggest that current smoking in particular may aggravate the rate of bone loss at older age and highlight implications for targeting this risk factor in populations that present higher smoking prevalence and vulnerability to bone fragility. [ABSTRACT FROM AUTHOR]

Abstract: We have developed a general framework which employs quantitative computed tomography (QCT) imaging and inter-subject image registration to model the three-dimensional structure of the hip, with the goal of quantifying changes in the spatial distribution of bone as it is affected by aging, drug treatment or mechanical unloading. We have adapted rigid and non-rigid inter-subject registration techniques to transform groups of hip QCT scans into a common reference space and to construct composite proximal femoral models. We have applied this technique to a longitudinal study of 16 astronauts who on average, incurred high losses of hip bone density during spaceflights of 4–6 months on the International Space Station (ISS). We compared the pre-flight and post-flight composite hip models, and observed the gradients of the bone loss distribution. We performed paired t-tests, on a voxel by voxel basis, corrected for multiple comparisons using false discovery rate (FDR), and observed regions inside the proximal femur that showed the most significant bone loss. To validate our registration algorithm, we selected the 16 pre-flight scans and manually marked 4 landmarks for each scan. After registration, the average distance between the mapped landmarks and the corresponding landmarks in the target scan was 2.56 mm. The average error due to manual landmark identification was 1.70 mm. [Copyright &y& Elsevier]