Medicine (Western Health) - Research Publications
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ItemAbnormal Trabecular Bone Score, Lower Bone Mineral Density and Lean Mass in Young Women With Premature Ovarian Insufficiency Are Prevented by Oestrogen Replacement(FRONTIERS MEDIA SA, 2022-05-19)BACKGROUND: Low bone density (BMD) and fractures commonly affect women with premature ovarian insufficiency (POI). However, bone microarchitecture and body composition data are lacking. OBJECTIVE: To assess and characterise musculoskeletal phenotype and effects of oestrogen replacement therapy (ERT) in women with POI. METHOD: Cross-sectional and longitudinal studies of 60 normal karyotype women with POI, aged 20-40 years, from 2005-2018. Dual x-ray absorptiometry (DXA)-derived spinal (LS) and femoral neck (FN) BMD, trabecular bone score (TBS), appendicular lean mass (ALM), total fat mass (TFM), and fracture prevalence were compared with 60 age-, and BMI-matched population-based controls. Longitudinal changes in bone and body composition variables and ERT effects were analysed using linear mixed models over a median duration of 6 years. RESULTS: Women with POI were subdivided into spontaneous (s)-POI (n=25) and iatrogenic (i)-POI (n=35). Median(range) age of POI diagnosis was 34 (10-40) years with baseline DXA performed at median 1(0-13) year post-diagnosis. ERT was used by 82% women (similar for both POI groups). FN-BMD were lowest in s-POI (p<0.002). Low TBS was more common in s-POI [(44%), p=0.03], versus other groups. LS-BMD and ALM were lower in both s-POI and i-POI groups than controls (p<0.05). Fracture prevalence was not significantly different: 20% (s-POI), 17% (i-POI), and 8% (controls) (p=0.26). Longitudinal analysis of 23 POI women showed regular ERT was associated with ALM increment of 127.05 g/year (p<0.001) and protected against bone loss. However, ERT interruption was associated with annual reductions in FN BMD and TBS of 0.020g/cm2 and 0.0070 (p<0.05), respectively. CONCLUSION: Deficits in BMD, trabecular microarchitecture, and lean mass were present in women with POI. However, regular ERT protected against declines in bone variables, with an increase in ALM. Assessment of skeletal and muscle health, and advocating ERT adherence, is essential in POI to optimise musculoskeletal outcomes.
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ItemNo Preview AvailableChanges in body composition in the year following critical illness: A case-control study(W B SAUNDERS CO-ELSEVIER INC, 2022-10)PURPOSE: To measure changes in dual x-ray absorptiometry (DXA) derived body composition in Intensive Care Unit (ICU) survivors in the year following discharge and compare to population controls. MATERIALS AND METHODS: Using prospective observational data changes in hip and spine DXA estimated lean and fat mass between ICU discharge and 1-year follow-up were calculated and compared with age-sex-height matched controls from the Geelong Osteoporosis Study via multivariable linear regression. RESULTS: Sixty-four participants were included, with median age 68.8 yr [IQR 60.8, 74.6], ICU length of stay 6.5 d [IQR 4, 9] and duration of mechanical ventilation 87 h [IQR 47, 143]. ICU survivors demonstrated greater annual increases in lean (+0.92 kg; 95%CI 0.67 to 1.18, p < 0.01) and fat mass (+2.50 kg, 95%CI 1.94 to 3.05; p < 0.01) than controls. At 1-yr follow-up, the ICU group had lower lean mass (-0.96 kg, 95%CI -1.91 to -0.01; p = 0.047) and greater fat mass (6.79 kg, 95%CI 4.55 to 9.03; p < 0.001). CONCLUSIONS: Mechanically ventilated adult ICU patients gained lean mass in the year following critical illness but did not reach the level of matched population-based peers. Understanding the factors associated with, and effect of increasing muscle mass and reducing fat mass in the year after critical illness requires further investigation.
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ItemNo Preview AvailableAssociations between parameters of peripheral quantitative computed tomography and bone material strength index(ELSEVIER SCIENCE INC, 2022-02-01)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%; β = 0.020, p = 0.006, tibia 4%; β = 0.020, p = 0.027 and cortical density: radius 4%; β = 4.160, p = 0.006, tibia 4%; β = 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 (β = 4.160, p = 0.053, β = 1.458, p = 0.027 respectively). Total area at the 66% tibial site was also associated with BMSi (β = 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.
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ItemNo Preview AvailableEstimation of Whole-Body and Appendicular Lean Mass from Spine and Hip Dual Energy X-ray Absorptiometry: A Cross-Sectional Study(SPRINGER, 2022-03-01)Whole-body dual X-ray absorptiometry (DXA) accurately measures lean mass but is not routinely used in clinical practice. Hip and spine DXA are used in the diagnosis of osteoporosis, and with the common co-occurrence of sarcopenia with osteoporosis, regional DXA scans provide an opportunity for assessment of lean mass. The aim of this study is to develop predictive equations for the estimation of whole-body lean mass (WBLM), appendicular lean mass (ALM) and whole-body fat mass (WBFM) from regional DXA scans. A total of 2427 participants (ages 20-96 year; 57.7% men) from the Geelong Osteoporosis Study who underwent both regional and whole-body DXA were included in the analysis. Using forward stepwise multivariable linear regression, percentage fat (spine%fat, hip%fat) values from lumbar spine and femoral neck DXA were used in combination with clinical data to develop and validate equations for the estimation of WBLM, WBFM and ALM. Mean age was 53.5 year (± 19.2), weight 78.2 kg (± 15.4), height 169.6 cm (± 9.4), WBLM 50.4 kg (± 11.1), ALM 22.8 kg (± 5.4) and WBFM 24.3 kg (± 10.4). Spine%fat (r = 0.21) and hip%fat (r = - 0.34) were correlated with whole-body lean mass (p < 0.001). Final predictive equations included age, sex, weight, height, spine%fat, and hip%fat and possessed high predictive value (Adj R2 0.91-0.94, RMSE 1.60-2.84 kg). K-fold cross-validation methods produced median root mean square error (RMSE) ranging from 1.59 to 2.81 kg for the three models. Regional DXA scans of the spine and hip can be used to estimate whole-body and appendicular lean mass, to assist in the identification of low muscle mass.
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ItemNo Preview AvailableLipopolysaccharide-binding protein and bone health: data from a population-based sample of men(SPRINGER LONDON LTD, 2023-02-01)UNLABELLED: We aimed to investigate the association between serum lipopolysaccharide-binding protein (LBP) and bone health in men. LBP was associated with lower bone density at the mid-forearm and the quantitative heel ultrasound measure, broadband ultrasound attenuation, for heavier participants. Data do not support clear associations between serum LBP and bone health. INTRODUCTION: The objective of this study was to investigate the association between serum lipopolysaccharide-binding protein (LBP) and potential downstream effects on skeletal density, quality, and turnover in a population-based sample of men. METHODS: This cross-sectional study utilised data from 1149 men (aged 20-96 year) enrolled in the Geelong Osteoporosis Study. Blood samples were obtained and lipopolysaccharide-binding protein (LBP), bone resorption marker, C-telopeptide (CTx), and formation marker, type 1 procollagen amino-terminal-propeptide (P1NP), were measured. Bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry. Stiffness Index (SI), broadband ultrasound attenuation (BUA), and speed of sound (SOS) were derived from quantitative heel ultrasound (QUS). Linear regression models were developed to test associations between log-transformed LBP (ln-LBP), BMD, QUS, and bone turnover, after adjusting for potential covariates. RESULTS: Serum LBP ranged from 1.07-208.53 ng/mL (median 16.53 ng/mL). Those with higher levels were older, less mobile, and had lower BMD at the mid-forearm, otherwise, groups were similar. Before and after adjustment for age, ln-LBP was associated with lower BMD at the spine, total body, and mid-forearm. Further adjustment for weight attenuated associations at the spine and total body, yet the relationship at the mid-forearm was sustained (β - 0.014 ± 0.004, p = 0.001). SOS and SI were not associated with ln-LBP either before or after adjustment for age; however, weight was identified as an effect modifier in the relationship between ln-LBP and BUA. An association was observed for those weighing greater than 82.7 kg (β 3.366 ± 0.929, p < 0.001), after adjustment for potential covariates. Neither bone turnover marker was associated with ln-LBP. CONCLUSION: Our data do not support a clear association between serum LBP and measures of bone health in this sample of men.
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ItemNo Preview AvailablePeripheral quantitative computed tomography-derived bone parameters in men with impaired fasting glucose and diabetes(SPRINGER JAPAN KK, 2023-01-01)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.
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ItemFatty Liver Index and Skeletal Muscle Density(SPRINGER, 2022-06)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.
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ItemLean mass as a risk factor for intensive care unit admission: an observational study(BMC, 2021-10-18)PURPOSE: Intensive care unit (ICU) survivors have reduced physical function likely due to skeletal muscle wasting and weakness acquired during critical illness. However, the contribution of pre-morbid muscle mass has not been elucidated. We aimed to examine the association between pre-ICU muscle mass and ICU admission risk. Secondary outcomes include the relationship between muscle mass and ICU outcomes. METHODS: ICU admissions between June 1, 1998, and February 1, 2019, were identified among participants of Geelong Osteoporosis Study (GOS), a population-based cohort study. Cox proportional hazard regression models estimated hazard ratios (HR) for ICU admission across T-score strata and continuous values of DXA-derived lean mass measures of skeletal mass index (SMI, lean mass/body mass %) and appendicular lean mass corrected for height (ALM/h2, kg/m2). Multivariable regression was used to determine the relationship between lean mass and ICU outcomes. RESULTS: One hundred and eighty-six of 3126 participants enrolled in GOS were admitted to the ICU during the follow-up period. In adjusted models, lean mass was not predictive of ICU admission (SMI: HR 0.99 95%CI 0.97-1.01, p = 0.32; ALM/h2: HR 1.11 95%CI 0.94-1.31, p = 0.23), while greater appendicular lean mass was related to reduced 28-day mortality (ALM/h2 adjOR: 0.25, 95%CI 0.10-0.63, p = 0.003, SMI adjOR: 0.91, 95%CI 0.82-1.02, p = 0.09). CONCLUSION: Lean mass was not associated with ICU admission in this population-based cohort study; however, greater appendicular lean mass was associated with reduced mortality. This suggests pre-ICU muscle status may not predict development of critical illness but is associated with better survival after critical illness occurs.
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ItemNormative data for peripheral quantitative computed tomography (pQCT) bone parameters in Australian men(ELSEVIER, 2021-12)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.
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