Gestational vitamin D and offspring fracture risk: do associations persist into mid adolescence?

BACKGROUND: Previous studies report that maternal vitamin D exposure during pregnancy is associated with offspring later-life bone health. A study in the Vitamin D in Pregnancy (VIP) cohort reported sexually dimorphic effects of maternal 25-hydroxyvitamin-D (25(OH)D) and offspring fracture profiles at 10 years of age. We, therefore, aimed to determine associations between maternal 25(OH)D status and offspring fracture risk at 16 years of age in this cohort. METHODS: In total, 475 mother-child pairs were recruited to the VIP study in southeastern Australia. Maternal serum samples were obtained at recruitment (<16 weeks' gestation) and/or 28-32 weeks' gestation and analysed for 25(OH)D. Radiologically-confirmed incident fractures in children were ascertained from date of birth (2002-2004) until July 16, 2019. Cox proportional hazard models were used to determine associations between maternal 25(OH)D and childhood fracture risk, and final models included maternal age at recruitment, offspring sex, birth weight, gestation length and season of 25(OH)D sample. RESULTS: Data were available for 400 children (mean age 16.1 years). There were 122 (30.5%) children who sustained at least one fracture. Higher maternal 25(OH)D (per 10 nmol/L) in early gestation was associated with a decreased fracture risk in boys (HR 0.87; 95% CI: 0.77, 0.99); the pattern was reversed in girls (HR 1.10; 95% CI 1.00, 1.22). At late gestation, higher maternal 25(OH)D was associated with an increased fracture risk in girls (HR 1.14; 95% CI: 1.04, 1.24). CONCLUSIONS: While our findings must be interpreted within the constraints of our limitations, we report that the contradictory risk profiles observed at early childhood in this cohort remain in adolescence.

Obesity and sarcopenic obesity characterized by low-grade inflammation are associated with increased risk for major depression in women.

Background: We aimed to determine women's risk of major depressive disorder (MDD) in relation to obesity phenotypes characterized by levels of circulating high-sensitivity C-reactive protein (hsCRP). Methods: This population-based retrospective cohort study comprised 808 women (ages 20-84 y) recruited 1994-1997 and followed for a median 16.1 y (IQR 11.9-16.8). At baseline, body fat and lean tissue mass were measured by whole body dual-energy x-ray absorptiometry (DXA). Obesity was identified as high fat mass index (>12.9 kg/m2), body fat percentage (≥35%) and body mass index (≥30 kg/m2); sarcopenic obesity referred to a high ratio fat mass/fat-free mass (≥0.80). Systemic inflammation was operationalized as serum hsCRP concentration in the upper tertile (>2.99 mg/L). Obesity phenotypes were: non-obese + lowCRP, non-obese + highCRP, obese + lowCRP, and obese + highCRP. During follow-up, the Structured Clinical Interview for DSM-IV-TR (SCID-I/NP) was used to identify lifetime history of MDD and age of onset. Poisson regression models were used to estimate the MDD rate for each obesity phenotype during follow-up. Demographic, health and lifestyle factors were tested as potential confounders. Results: During 11,869 p-y of follow-up, 161 (19.9%) women experienced an MDD episode. For obesity phenotypes based on fat mass index, models adjusted for baseline age and prior MDD, and non-obese + lowCRP as reference, RR for non-obese + highCRP was 1.21 (95% CI 0.80, 1.82), obese + lowCRP 1.46 (0.86, 2.47) and obese + highCRP 1.56 (1.03, 2.37). Patterns were similar for obesity by body fat percentage, body mass index and sarcopenic obesity. Conclusion: Consistently across different obesity definitions, this longitudinal study reports that women with both obesity and systemic inflammation are at increased risk of subsequent MDD. Future research should examine whether tackling this metabolically unhealthy obesity type - through, for example, lifestyle or medication approaches - can reduce depression risk.

Associations Between Aldosterone-Renin-Ratio and Bone Parameters Derived from Peripheral Quantitative Computed Tomography and Impact Microindentation in Men.

Components of the renin-angiotensin-aldosterone system (RAAS) are present on bone cells. One measure of RAAS activity, the aldosterone-renin-ratio (ARR), is used to screen for primary aldosteronism. Associations between ARR and bone mineral density are conflicting. This study investigated associations between ARR and peripheral quantitative computed tomography (pQCT) and impact microindentation (IMI). Male participants (n = 431) were from the Geelong Osteoporosis Study. "Likely" primary aldosteronism was defined as ARR ≥ 70 pmol/mIU. Another group, "possible" primary aldosteronism, was defined as either ARR ≥ 70 pmol/mIU or taking a medication that affects the RAAS, but not a beta blocker, and renin < 15 mU/L. Using pQCT, images at 4% and 66% of radial (n = 365) and tibial (n = 356) length were obtained. Using IMI measurements, bone material strength index (BMSi; n = 332) was determined. Associations between ARR or likely/possible primary aldosteronism and IMI or pQCT-derived bone parameters were tested using median regression. ARR and aldosterone values were not associated with any of the pQCT-derived bone variables in either unadjusted or adjusted analyses. Men with likely primary aldosteronism (n = 16), had lower adjusted total bone area (radial 66% site, - 12.5%). No associations were observed for men with possible primary aldosteronism (unadjusted or adjusted). No associations with BMSi were observed (p > 0.05). There were no associations between ARR or aldosterone and pQCT-derived bone parameters. Men with likely primary aldosteronism had lower bone area, suggesting clinically high levels of ARR may have a negative impact on bone health.

Peripheral quantitative computed tomography-derived bone parameters in men with impaired fasting glucose and diabetes.

INTRODUCTION: Individuals with type 2 diabetes mellitus (T2DM) are at higher risk of fracture, but paradoxically do not have reduced bone mineral density. We investigated associations between peripheral quantitative computed tomography (pQCT) and glycaemia status. MATERIALS AND METHODS: Participants were men (n = 354, age 33-92 year) from the Geelong Osteoporosis Study. Diabetes was defined by fasting plasma glucose (FPG) ≥ 7.0 mmol/L, self-report of diabetes and/or antihyperglycaemic medication use and impaired fasting glucose (IFG) as FPG 5.6-6.9 mmol/L. Bone measures were derived using pQCT (XCT2000) at 4% and 66% radial and tibial sites. Linear regression was used, adjusting for age, body mass index and socio-economic status. RESULTS: At the 4% site, men with T2DM had lower adjusted bone total area, trabecular area and cortical area at the radius (all - 6.2%) and tibia (all - 6.4%) compared to normoglycaemia. Cortical density was higher for T2DM at the radius (+ 5.8%) and tibia (+ 8.0%), as well as adjusted total bone density at the tibial site (+ 6.1%). At the 66% site, adjusted total bone area and polar stress strain index were lower for T2DM at the radius (- 4.3% and - 8.0%). Total density was also higher for T2DM (+ 1.2%). Only cortical density at the 4% tibial site was different between IFG and normoglycaemia in adjusted analyses (+ 4.5%). CONCLUSION: Men with T2DM had lower total bone area, trabecular area, cortical area and polar stress strain index than the other two groups; however, total density and cortical density were higher. Only one difference was observed between IFG and normoglycaemia; increased tibial cortical density.

How Well Do Low Population-Specific Values for Muscle Parameters Associate with Indices of Poor Physical Health? Cross-Sectional Data from the Geelong Osteoporosis Study.

We aimed to examine associations between skeletal muscle deficits and indices of poor health. Cut-points for skeletal muscle deficits were derived using data from the Geelong Osteoporosis Study and definitions from the revised European Consensus on Definition and Diagnosis and the Foundation for the National Institutes of Health. Participants (n = 665; 323 women) aged 60-96 year had handgrip strength measured by dynamometry and appendicular lean mass by whole-body dual-energy X-ray absorptiometry. Physical performance was assessed using the Timed Up and Go test. Sex-specific cut-points were equivalent to two standard deviations below the mean young reference range from the Geelong Osteoporosis Study. Indices of poor health included fractures, falls, and hospitalisations. Low trauma fractures since age 50 year (excluding skull, face, digits) were self-reported and confirmed using radiological reports. Falls (≥1 in the past 12 months) and hospitalisations (past month) were self-reported. Logistic regression models (age- and sex-adjusted) were used to examine associations. Receiver Operating Characteristic curves were applied to determine optimal cut-points for handgrip strength, Timed Up and Go, appendicular lean mass/height2, and appendicular lean mass/body mass index that discriminated poor health outcomes. There were 48 participants (6.9%) with hospitalisations, 94 (13.4%) with fractures, and 177 (25.3%) with at least one fall (≥1). For all cut-points, low handgrip strength was consistently associated with falls. There was little evidence to support an association between low appendicular lean mass, using any cut-point, and indices of poor health. Optimal cut-offs for predicting falls (≥1) were: handgrip strength 17.5 kg for women and 33.5 kg for men; Timed Up and Go 8.6 s for women and 9.9 s for men; appendicular lean mass/height2 6.2 kg/m2 for women and 7.46 kg/m2 for men; and appendicular lean mass/body mass index 0.6 m2 for women and 0.9 m2 for men. In conclusion, muscle strength and function performed better than lean mass to indicate poor health. These findings add to the growing evidence base to inform decisions regarding the selection of skeletal muscle parameters and their optimal cut-points for identifying sarcopenia.

Association between maternal adversity, DNA methylation, and cardiovascular health of offspring: a longitudinal analysis of the ALSPAC cohort study.

OBJECTIVES: Maternal adversity during pregnancy has been shown to be associated with some health outcomes in the offspring. This study investigated the association of maternal adversity during pregnancy and DNA methylation with offspring cardiovascular (CV) health. DESIGN: Longitudinal observational cohort study SETTING: All pregnant residents in county Avon (∼0.9 million), UK, were eligible to participate if their estimated delivery date was between 1 April 1991 and 31 December 1992. PARTICIPANTS: Mother-offspring pairs enrolled in the Avon Longitudinal Study of Parents and Children cohort at seven (n=7431) and 17 years of age (n=3143). PRIMARY AND SECONDARY OUTCOME MEASURES: Offspring CV health primary measures were heart rate (HR), blood pressure (BP) and secondary measures were pulse-wave velocity and carotid intima-media thickness. RESULTS: Overall, there was no association between maternal adversity scores (number or perceived impact) and primary CV measures (Perceived impact; HR: 0.999-fold change 95% CI 0.998 to 1.001; systolic BP (SBP): 1.000-fold change 95% CI 0.999 to 1.001; diastolic BP: 1.000-fold change 95% CI 0.999 to 1.002). Some small offspring sex effects were observed and there was also a small association between methylation of some CpG sites and offspring BP measures. CONCLUSIONS: We found little evidence to support the overall association of maternal adversity during pregnancy and DNA methylation with offspring CV measures. Offspring sex-specific and age-specific associations require further investigation.

Fatty Liver Index and Skeletal Muscle Density.

Accumulation of fat in the liver and skeletal muscle is associated with obesity and poor health outcomes. Liver steatosis is a characteristic of non-alcoholic fatty liver disease (NAFLD) and myosteatosis, of poor muscle quality in sarcopenia. In this study of 403 men (33-96 years), we investigated associations between the fatty liver index (FLI) and muscle density, as markers of fat accumulation in these organs. We also investigated associations between the FLI and parameters of sarcopenia, including DXA-derived appendicular lean mass (ALM) and handgrip strength by dynamometry. Muscle density was measured using pQCT at the radius and tibia. FLI was calculated from BMI, waist circumference, and levels of triglycerides and gamma-glutamyltransferase. There was a pattern of decreasing muscle density across increasing quartiles of FLI. After adjusting for age and lifestyle, mean radial muscle density in Q4 was 2.1% lower than Q1 (p < 0.001) and mean tibial muscle density was 1.8% lower in Q3 and 3.0% lower in Q4, compared to Q1 (p = 0.022 and < 0.001, respectively). After adjusting for age and sedentary lifestyle, participants in the highest FLI quartile were sixfold more likely to have sarcopenia. In conclusion, our results suggest that fat accumulation in the liver co-exists with fat infiltration into skeletal muscle.

Associations between parameters of peripheral quantitative computed tomography and bone material strength index.

BACKGROUND: Bone material strength index (BMSi) is measured in vivo using impact microindentation (IMI). However, the associations between BMSi and other bone measures are not clear. This study investigated whether bone parameters derived by peripheral quantitative computed tomography (pQCT) are associated with BMSi. METHODS: Participants were men (n = 373, ages 34-96 yr) from the Geelong Osteoporosis Study. BMSi was measured using an OsteoProbe (Active Life Scientific, USA). Bone measures were obtained at both the radius (n = 348) and tibia (n = 342) using pQCT (XCT 2000 Stratec Medizintechnik, Germany). Images were obtained at 4% and 66% of radial and tibial length. Associations between pQCT parameters and BMSi were tested using Spearman's correlation and multivariable regression used to determine independent associations after adjustment for potential confounders. Models were checked for interaction terms. RESULTS: Weak associations were observed between total bone density (radius 4%; r = +0.108, p = 0.046, tibia 4%; r = +0.115, p = 0.035), cortical density (tibia 4%; r = +0.123, p = 0.023) and BMSi. The associations were independent of weight, height, and glucocorticoid use (total bone density: radius 4%; ß = 0.020, p = 0.006, tibia 4%; ß = 0.020, p = 0.027 and cortical density: radius 4%; ß = 4.160, p = 0.006, tibia 4%; ß = 0.038, p = 0.010). Associations with bone mass were also observed at the 66% radial and tibial site, independent of age, weight, and glucocorticoid use (ß = 4.160, p = 0.053, ß = 1.458, p = 0.027 respectively). Total area at the 66% tibial site was also associated with BMSi (ß = 0.010, p = 0.012), independent of weight and glucocorticoid use. No interaction terms were identified. CONCLUSION: There were weak associations detected between some pQCT-derived bone parameters and BMSi.

Associations Between Muscle Quality and Cognitive Function in Older Men: Cross-Sectional Data From the Geelong Osteoporosis Study.

Sarcopenia-related declines appear to be adversely associated with cognition in the elderly. Poor muscle quality is a marker for sarcopenia, yet little research has examined the concurrence of poor muscle quality and poor cognition. The aim of this study was to investigate the association between muscle quality and cognitive function, overall and in specific domains, in older men. This study involved 342 men from the Geelong Osteoporosis Study (ages 60-96 years). Handgrip strength (HGS, kg) was measured by dynamometry (Vernier, LoggerPro3), and lean mass of arms (kg) and appendicular lean mass (ALM, kg) by dual-energy X-ray absorptiometry (Lunar). Muscle quality was expressed as HGS/(arm lean mass) (kg/kg) as well as HGS/ALM (kg/kg). Cognitive function was assessed in 4 domains: visual attention, psychomotor function, working memory and visual learning. Overall cognitive function scores were calculated. Higher scores represent poorer cognitive performance in attention, psychomotor function and working memory, but better performance for visual memory/learning and overall cognitive function. Additionally, cognitive impairment was determined by the mini-mental state exam (score ≤ 24). Linear regression analyses and logistic regression were performed. There were age-related declines observed for all measures relating to muscle and cognition. Muscle quality (HGS/arm lean mass) was associated with all cognition assessments before and after adjusting for age, except for age-adjusted working memory. Muscle quality (HGS/arm lean mass) was associated with psychomotor function (B -0.01, 95% CI -0.02, -0.005) and overall cognitive function (b + 0.07, 95% CI 0.03, 0.11) after adjusting for age and education. Greater muscle quality was also associated with the likelihood of cognitive impairment OR 0.64 (95%CI 0.46-0.88) after adjusting for age; associations with attention and visual memory/learning were attenuated after further adjustment for confounders. Similar patterns were observed when muscle quality was determined as HGS/ALM. Our data support an association between muscle quality and cognitive function. Further research is needed to examine temporal changes between the Two.

Peripheral quantitative computed tomography (pQCT) measures are associated with prior low trauma fracture in men.

Peripheral quantitative computed tomography (pQCT) assesses bone quantity and quality, complementary to current standard practice, and has potential to improve prediction of fracture risk. This study explored whether pQCT parameters were associated with prior fracture in men and found a number of parameters to be associated, particularly at the radius. PURPOSE: Peripheral quantitative computed tomography (pQCT) provides information about bone structure and density complementary to dual x-ray absorptiometry. This study aimed to determine which pQCT parameters are associated with prior fracture. METHODS: Participants were men (n = 508, age 33-96 years) from the Geelong Osteoporosis Study. Parameters at 4% (n = 469) and 66% (n = 436) of radial length, and 4% (n = 449) and 66% (n = 437) of tibial length were acquired (pQCT XCT 2000, Stratec Medizintechnik, Pforzheim, Germany), and mean standardised. Low trauma prior fractures in adulthood (≥ age 20 years) were radiologically confirmed when possible. Cross-sectional associations between pQCT and fracture were tested using logistic regression adjusting for confounders. RESULTS: Prior low trauma fractures were identified for 106 participants. Fracture was negatively associated with parameters at the 4% radius site: bone mass (adjusted OR = 0.67; 95%CI = 0.52-0.86), total density (OR = 0.61; 95%CI = 0.47-0.78), trabecular density (OR = 0.62; 95%CI = 0.48-0.79) and cortical subdensity (OR = 0.61; 95%CI = 0.47-0.77). At the 66% radius site, fracture was associated with total density (OR = 0.69; 95%CI = 0.55-0.87) and cortical thickness (OR = 0.68; 95%CI = 0.54-0.86). Fracture was associated with the ratio of the cortical area at the 66% site to the total area at the 4% site (OR = 0.74; 95%CI = 0.58-0.94). Prior fracture was negatively associated with parameters at the 4% tibial site: total density (OR = 0.67; 95%CI = 0.52-0.86), trabecular density (OR = 0.64; 95%CI = 0.50-0.82) and cortical subdensity (OR = 0.72; 95%CI = 0.56-0.92). Fracture was negatively associated with cortical density at the 66% site (OR = 0.74; 95%CI = 0.58-0.94), and the ratio of the cortical area at the 66% site to the total area at the 4% site (OR = 0.65; 95%CI = 0.46-0.91), but were attenuated in adjusted models. No other associations were identified. CONCLUSION: Prior fracture was associated with parameters at both the radius and tibia. This study highlights key pQCT parameters that may aid in the prediction of fracture risk.

Maternal vitamin D and offspring fracture risk: the Vitamin D in Pregnancy study.

Vitamin D is important for bone health and strength. Previous studies report 25-hydroxyvitamin D (25(OH)D) exposure during pregnancy may impact offspring bone health later in life. In this study, maternal 25(OH)D at recruitment was associated with a lower fracture risk in boys and an increased fracture risk in girls at 28-32 weeks gestation. PURPOSE: Maternal 25-hydroxyvitamin D (25(OH)D) in pregnancy has been shown to be associated with offspring bone measures in some studies, but few have examined fracture risk. We aimed to determine associations between maternal vitamin D status and offspring fracture risk. METHODS: In total, 475 mother-child pairs participating in the Vitamin D in Pregnancy study in southeastern Australia were recruited. Maternal serum samples were taken at recruitment (< 16 weeks gestation) and/or 28-32 weeks gestation and analysed for 25(OH)D. Incident fractures in children were ascertained from date of birth (2002-2004) until December 31, 2012. Cox proportional hazard models included maternal age at recruitment, offspring sex, birth weight, gestation length and season of vitamin D sample. RESULTS: Complete follow-up data were available for 400 children (median age = 9.5 years). There were 68 (17.0%) children who sustained at least one fracture. Higher maternal 25(OH)D (per 10 nmol/L) in early gestation was weakly associated with a decreased fracture risk in boys (HR 0.82; 95% CI 0.68, 0.99; p = 0.048) but not girls (HR 1.10; 95% CI 0.98, 1.25; p = 0.11). At late gestation, higher maternal 25(OH)D was associated with increased fracture risk in girls (HR 1.11; 95% CI 1.01, 1.23; p = 0.038) but not boys (HR 0.94; 95% CI 0.80, 1.10; p = 0.42). No statistically significant relationships were detected in analyses investigating 25(OH)D as a categorical variable. CONCLUSION: There is some evidence that higher maternal 25(OH)D at recruitment was associated with lower fracture risk in boys, while higher maternal 25(OH)D at 28-32 weeks gestation was associated with an increased fracture risk in girls.

High Alcohol Intake in Older Men and the Probability of Osteoporotic Fracture According to the FRAX Algorithm.

We aimed to determine the contribution of high alcohol intake to fracture probability, calculated using a fracture-risk assessment tool (FRAX). Participants were 262 men (ages 60-90 y) in the Geelong Osteoporosis Study. Alcohol consumption was documented via a food frequency questionnaire; 46 (17.6%) consumed three or more units per day, fulfilling the criterion for high alcohol intake. Bone mineral density (BMD) was measured by dual energy x-ray absorptiometry. We determined FRAX probabilities (%) for major osteoporotic fracture (MOF) and hip fracture (HF), calculated with and without alcohol intake. Thresholds for high FRAX probabilities, calculated with or without BMD, were ≥20% for MOF and ≥3% for HF. Proportions of men with high HF-FRAX probabilities were consistently greater for drinkers compared with non-drinkers. For drinkers, paired differences showed that median MOF-FRAXwithoutBMD probabilities calculated with and without alcohol changed by -2.3, HF-FRAXwithoutBMD by -1.7, MOF-FRAXwithBMD by -1.4, and HF-FRAXwithBMD by -0.9 (all p < 0.001). We estimated that, should drinkers lower their alcohol consumption to <3 units/d, up to 66.7% of those at high risk for MOF and up to 41.0% at high risk for HF would reduce their FRAX probabilities to below the thresholds for high fracture risk. In the context of the Australian environment, these data describe the extent to which older men with high alcohol consumption are at increased risk for fracture.

Normative data for peripheral quantitative computed tomography (pQCT) bone parameters in Australian men.

BACKGROUND: Peripheral quantitative computed tomography (pQCT) can provide information complementary to dual x-ray absorptiometry (DXA), however, there is sparse normative data to enable meaningful clinical interpretation and comparison. This study aimed to develop age-stratified normative data for pQCT-derived bone parameters in Australian men. METHODS: Participants were men (n = 508, age 33-96 yr) from the Geelong Osteoporosis Study. Bone parameters at 4% (n = 469) and 66% (n = 436) of radial length, and 4% (n = 449) and 66% (n = 438) of tibial length were acquired using pQCT (XCT 2000, Stratec Medizintechnik, Pforzheim, Germany). Best models of age, height and weight for each parameter were developed and where parameters exhibited variation with age, age decade mean (±SD) values were determined. Scatterplots were used to visualise the relationships between each of the parameters and age, height and weight. RESULTS: Thirteen parameters at tibial and radial sites were correlated with age, height and weight, allowing for their inclusion in multiple linear regression models. A positive association with age was found for total area of the tibia or radius (as appropriate) (mm2) at all sites, trabecular bone area (mm2) at 4% sites, and total bone area (both long bones) (mm2) at 66% sites. A negative association with age was found for cortical density (mg/cm3) and cortical thickness (mm) at both radial and tibial 66% sites, but total density (mg/cm3) at the 66% radial site and total cortical density of both long bones (mg/cm3) at the 66% tibial site only. CONCLUSION: This study presents normative data for pQCT-derived bone parameters and describes age related associations in a number of these variables. Broadly, parameters of bone area were positively associated with age, whereas parameters associated with bone density and structure were negatively associated with age. These data have the potential to be used in clinical settings when assessing age-related decline in bone health. MINI ABSTRACT: Normative data for pQCT parameters in Australian men are presented, adjusted for age, height and weight.

The Dietary Inflammatory Index Is Associated with Low Muscle Mass and Low Muscle Function in Older Australians.

Age-associated chronic, low grade systemic inflammation has been recognised as an important contributing factor in the development of sarcopenia; importantly, diet may regulate this process. This cross-sectional study examined the association of diet-related inflammation with components of sarcopenia. Participants (n = 809) aged 60-95 years from the Geelong Osteoporosis Study were studied. Body composition was measured by dual energy X-ray absorptiometry. In this study, low appendicular lean mass (ALM/height2, kg/m2) was defined as T-score < -1 and low muscle function as Timed-Up-and-Go >10 s over 3 m (TUG > 10). Dietary inflammatory index (DII®) scores, based on specific foods and nutrients, were computed using dietary data collected from a food frequency questionnaire. Associations between DII scores and low muscle mass and low muscle function, alone and combined, were determined using linear and logistic regression. After adjusting for covariates, higher DII score was associated with lower ALM/height2 (ß -0.05, standard error (SE) 0.02, p = 0.028), and higher natural log-transformed (ln) (TUG) (ß 0.02, standard error 0.01, p = 0.035) and higher likelihood for these components combined (odds ratio 1.33, 95% confidence interval 1.05 to 1.69, p = 0.015). A pro-inflammatory diet, as indicated by higher DII score, is associated with lower muscle mass, poorer muscle function and increased likelihood for the combination of low muscle mass and low muscle function. Further studies investigating whether anti-inflammatory dietary interventions could reduce the risk of sarcopenia are needed.

Prevalence of Sarcopenia Employing Population-Specific Cut-Points: Cross-Sectional Data from the Geelong Osteoporosis Study, Australia.

BACKGROUND: Prevalence estimates for sarcopenia vary depending on the ascertainment criteria and thresholds applied. We aimed to estimate the prevalence of sarcopenia using two international definitions but employing Australian population-specific cut-points. METHODS: Participants (n = 665; 323 women) aged 60-96 years old were from the Geelong Osteoporosis Study. Handgrip strength (HGS) was measured by dynamometers and appendicular lean mass (ALM) by whole-body dual-energy X-ray absorptiometry. Physical performance was assessed using gait speed (GS, men only) and/or the timed up-and-go (TUG) test. Using cut-points equivalent to two standard deviations (SDs) below the mean young reference range from the same population and recommendations from the European Working Group on Sarcopenia in Older People (EWGSOP), sarcopenia was identified by low ALM/height2 (<5.30 kg for women; <6.94 kg for men) + low HGS (<16 kg women; <31 kg men); low ALM/height2 + slow TUG (>9.3 s); low ALM/height2 + slow GS (<0.8 m/s). For the Foundation for the National Institutes of Health (FNIH) equivalent, sarcopenia was identified as low ALM/BMI (<0.512 m2 women, <0.827 m2 men) + low HGS (<16 kg women, <31 kg men). Receiver Operating Characteristic curves were also applied to determine optimal cut-points for ALM/BMI (<0.579 m2 women, <0.913 m2 men) that discriminated poor physical performance. Prevalence estimates were standardized to the Australian population and compared to estimates using international thresholds. RESULTS: Using population-specific cut-points and low ALM/height2 + HGS, point-estimates for sarcopenia prevalence were 0.9% for women and 2.9% for men. Using ALM/height2 + TUG, prevalence was 2.5% for women and 4.1% for men, and using ALM/height2 + GS, sarcopenia was identified for 1.6% of men. Using ALM/BMI + HGS, prevalence estimates were 5.5-10.4% for women and 11.6-18.4% for men. CONCLUSIONS: This study highlights the range of prevalence estimates that result from employing different criteria for sarcopenia. While population-specific criteria could be pertinent for some populations, a consensus is needed to identify which deficits in skeletal muscle health are important for establishing an operational definition for sarcopenia.

Gestational Folate and Offspring Bone Health; The Vitamin D in Pregnancy Study.

Maternal nutritional intake, such as folate and folic acid supplementation, during pregnancy may affect offspring bone health during childhood. We aimed to determine the associations between maternal dietary and supplementary folate intake and offspring bone health measures, including fracture risk. Data were obtained from 160 of 475 mother-child pairs who had returned for the 11-year follow up of the Vitamin D in Pregnancy Study, an observational cohort study. Incident fractures were ascertained from radiological records and dual X-ray absorptiometry was used to measure bone mineral density and content at 11 years of age. Maternal dietary folate intake during pregnancy was determined by Food Frequency Questionnaire and folate supplementation was determined through self-report. Both measures were undertaken at recruitment (before 16 weeks gestation) and at 28-32 weeks' gestation. Multivariable linear regression models and Cox regression models were used to examine associations. Results are presented as per 1000 µg folate for dietary measures. There were significant associations between maternal folate supplementation in early pregnancy (< 16 weeks gestation) and offspring spine bone mineral content (BMC) (ß = 1.53, 95% CI 0.21, 2.86), spine area (ß = 1.10, 95% CI 0.37, 1.82) and total body less head area (ß = 329.30, 95% CI 3.50, 55.20) at the 11-year follow-up. The association between spine BMC was attenuated after adjustment for bone size (ß = 0.13 95% CI - 0.85, 1.10). There was no association between maternal folate supplementation at 28-32 weeks' or maternal dietary intake at either time point with any offspring bone outcome. These data suggest that folate supplementation in early pregnancy may be associated with offspring bone size, but not other bone measures.

Dynapenia and Low Cognition: A Cross-Sectional Association in Postmenopausal Women.

Dynapenia is a key contributor to physical frailty. Cognitive impairment and dementia accompany frailty, yet links between skeletal muscle and neurocognition are poorly understood. We examined the cross-sectional relationship between lower limb muscle strength and global cognitive function. Participants were 127 women aged 51-87 years, from the Geelong Osteoporosis Study. Peak eccentric strength of the hip-flexors and hip abductors was determined using a hand-held dynamometer, and dynapenia identified as muscle strength t-scores < -1. Cognition was assessed using the Mini-Mental State Examination (MMSE), and MMSE scores below the median were rated as low. Associations between dynapenia and low cognition were examined using logistic regression models. Hip-flexor dynapenia was detected in 38 (71.7%) women with low cognition and 36 (48.7%) with good cognition (p = 0.009); for hip abductor dynapenia, the pattern was similar (21 (39.6%) vs. 9 (12.2%); p < 0.001). While the observed difference for hip-flexor strength was attenuated after adjusting for age and height (adjusted Odds Ratio (OR) 1.95, 95%CI 0.86-4.41), low cognition was nearly 4-fold more likely in association with hip abductor dynapenia (adjusted OR 3.76, 95%CI 1.44-9.83). No other confounders were identified. Our data suggest that low strength of the hip abductors and low cognition are associated and this could be a consequence of poor muscle function contributing to cognitive decline or vice versa. As muscle weakness is responsive to physical interventions, this warrants further investigation.

Skeletal Muscle Density and Cognitive Function: A Cross-Sectional Study in Men.

We aimed to investigate cross-sectional associations between skeletal muscle density, a proxy measure for fatty infiltration into muscle, and cognition. Contributions from body fat mass, systemic inflammation and lifestyle were explored, as these factors have been identified in both muscle and cognitive deterioration. For 281 men (60-95 year) from the Geelong Osteoporosis Study, radial and tibial muscle density were measured using peripheral quantitative computed tomography. Body fat and appendicular lean mass were measured using dual-energy X-ray absorptiometry. Cognitive function was assessed for psychomotor function (DET), visual identification/attention (IDN), visual learning (OCL) and working memory (OBK) (CogState Brief Battery). Composite scores signified overall cognitive function (OCF). Higher scores represent poorer performance except for OCL and OCF. Regression analyses examined associations between muscle density and cognition; potential confounders included age, muscle cross-sectional area (CSA), body composition, lifestyle and serum markers of inflammation. Negative associations with age were evident for muscle density, all cognitive domains and OCF. Muscle density at both sites was positively associated with DET, OCL and OCF. After adjustment for age, the association persisted for DET (radius: B = - 0.006, p = 0.02; tibia: B = - 0.003, p = 0.04) and OCL (radius B = + 0.004, p = 0.02; tibia: B = + 0.005, p < 0.001). At the radius, further adjustment for serum TNF-α explained the association between muscle density (B = - 0.002, p = 0.66) and DET. Education and physical activity contributed to the model for radial muscle density and DET. There were no contributions from muscle CSA, appendicular lean mass, body fat mass, other markers of inflammation or other potential confounders. At the tibia, the association between muscle density and DET (B = - 0.003, p = 0.04) was independent of TNF-α. There was an age-adjusted association between muscle density and OCL at both sites (radius: B = + 0.004, p = 0.02; tibia: B = + 0.005, p < 0.001). None of the potential confounders contributed to the models. Muscle density was associated with cognitive function in the DET and OCL domains. However, there was little evidence that this was explained by inflammation or body fat mass. No associations were identified between muscle density and IDN or OBK.

Gestational Vitamin D and Offspring Bone Measures: Is the Association Independent of Maternal Bone Quality?

Previously we have reported an association between maternal vitamin D and offspring bone as measured by dual-energy X-ray absorptiometry. It is plausible that shared genetics might confound associations between maternal vitamin D in pregnancy and offspring bone measures. We aimed to determine whether such associations are independent of maternal bone quality. Data for this analysis were derived from 168 mother-child pairs who returned at the 11-year follow-up of the vitamin D in pregnancy study. Gestational 25-hydroxyvitamin D [25(OH)D] was assessed by radioimmunoassay in early pregnancy at recruitment (before 16 weeks gestation) and later in pregnancy (28-32 weeks gestation). Bone quality was assessed for mothers and children at the calcaneus using quantitative ultrasound (Achilles InSight, GE). Speed of Sound (SOS), Broadband Ultrasound Attenuation (BUA) and Stiffness Index (SI) were the outcomes of interest. Maternal 25(OH)D in early pregnancy was associated with offspring SOS (ß 1.46 m/s 95% CI 0.12, 2.8). When separated by sex, there was no association between maternal 25(OH)D at recruitment and offspring SI (r = - 0.05, p = 0.68), SOS (r = 0.11, p = 0.34) or BUA (- 0.09, p = 0.43) in girls. In boys, maternal 25(OH)D at recruitment was associated with SI (r = 0.21, p = 0.048), and SOS (r = 0.24, p = 0.03) but not BUA (r = 0.10, p = 0.37). Adjustment for the offspring factors and respective maternal QUS parameter did not attenuate associations between maternal 25(OH)D in early pregnancy with offspring SOS, nor SI. There was no association with BUA. Furthermore, there was no association between maternal 25(OH)D in late pregnancy with any offspring QUS parameter. These prospective data support existing evidence of a positive relationship between maternal 25(OH)D levels during early pregnancy and measures of bone health of offspring in childhood, independent of maternal bone phenotype.

Physical and lifestyle factors associated with trabecular bone score values.

TBS is associated with age, weight, childhood physical activity, and BMD in men and age, height, BMD, and mobility in women. INTRODUCTION: Trabecular bone score (TBS) indirectly assesses trabecular microarchitecture at the lumbar spine, providing complementary information to areal BMD. Many studies have investigated the relationships between BMD and lifestyle factors known to affect bone, but such research is limited for TBS. The aim of this study was to assess the relationship between TBS and lifestyle factors in Australian men and women. METHODS: This cross-sectional study involved 894 men and 682 women (ages 24-98 years) enrolled in the Geelong Osteoporosis Study. TBS was assessed by analysis of lumbar spine DXA scans (Lunar Prodigy) using TBS iNsight software (Version 2.2). Bivariate and multivariable linear regression models were used to explore the associations between TBS and physical and lifestyle factors, including anthropometry, alcohol consumption, childhood physical activity, mobility, smoking status, prior low trauma fracture, medication use, and intakes of calcium and vitamin D. RESULTS: In bivariate regression modelling, low mobility and the use of antiresorptive medication were associated with lower TBS in both men and women. Low childhood physical activity was also associated with lower TBS in men. Prior fracture, use of glucocorticosteroids, and total calcium intake were also associated with lower TBS in women. The final adjusted model for men included age, weight, childhood physical activity, and BMD, and for women, age, height, BMD, and mobility. No interaction terms were identified in the models. CONCLUSIONS: Lower TBS is associated with older age, increased weight, low childhood physical activity, and lower BMD in men and older age, shorter stature, lower BMD, and low mobility in women.