Medicine (Western Health) - Research Publications

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    Abnormal Trabecular Bone Score, Lower Bone Mineral Density and Lean Mass in Young Women With Premature Ovarian Insufficiency Are Prevented by Oestrogen Replacement
    Samad, N ; Nguyen, HH ; Hashimura, H ; Pasco, J ; Kotowicz, M ; Strauss, BJ ; Ebeling, PR ; Milat, F ; Vincent, AJ (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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    Associations between dairy consumption and constipation in adults: A cross-sectional study.
    Aslam, H ; Mohebbi, M ; Ruusunen, A ; Dawson, SL ; Williams, LJ ; Berk, M ; Holloway-Kew, KL ; Collier, F ; Loughman, A ; Pasco, JA ; Jacka, FN (SAGE Publications, 2022-03)
    OBJECTIVE: The current study aimed to assess the association between dairy consumption and constipation in the general adult population. DESIGN: Data from the Geelong Osteoporosis Study were used to assess the association between dairy consumption and constipation in women (n=632) and men (n=609). Information on milk, yogurt and cheese, and constipation were self-reported. Total dairy was calculated by summing the intake of milk, yogurt and cheese and expressed as servings per day. Multivariable logistic regression models adjusted for irritable bowel syndrome, major depressive disorders, mobility, body mass index, age and fibre intake were used to examine the odds ratio (OR) and 95% confidence interval (CI) between the consumption of categories of total dairy, milk, yogurt, cheese, and constipation. RESULTS: In women, consumption of 1-2 servings/d of total dairy was associated with reduced odds for constipation (OR: 0.49; 95% CI: 0.26-0.90; P=0.021) compared to consuming <1 serving/d of total dairy after adjusting for covariates. Also, consumption of 1-4 servings/d of milk was associated with marginally reduced odds for constipation (OR: 0.63; 95% CI: 0.39-1.02; P=0.058) compared to women who consumed <1 serving/d of milk after adjusting for covariates. There were no significant associations detected between other types of dairy consumption and constipation in women, and none in men. CONCLUSION: In women, consumption of moderate amounts of dairy is associated with reduced odds for constipation whereas in men no associations were detected between dairy consumption and constipation. Further studies are warranted to confirm results.
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    Comparison of the Accuracy of the 7-Item HADS Depression Subscale and 14-Item Total HADS for Screening for Major Depression: A Systematic Review and Individual Participant Data Meta-Analysis
    Wu, Y ; Levis, B ; Daray, FM ; Ioannidis, JPA ; Patten, SB ; Cuijpers, P ; Ziegelstein, RC ; Gilbody, S ; Fischer, FH ; Fan, S ; Sun, Y ; He, C ; Krishnan, A ; Neupane, D ; Bhandari, PM ; Negeri, Z ; Riehm, KE ; Rice, DB ; Azar, M ; Yan, XW ; Imran, M ; Chiovitti, MJ ; Boruff, JT ; McMillan, D ; Kloda, LA ; Markham, S ; Henry, M ; Ismail, Z ; Loiselle, CG ; Mitchell, ND ; Al-Adawi, S ; Beck, KR ; Beraldi, A ; Bernstein, CN ; Boye, B ; Buel-Drabe, N ; Bunevicius, A ; Can, C ; Carter, G ; Chen, C-K ; Cheung, G ; Clover, K ; Conroy, RM ; Costa-Requena, G ; Cukor, D ; Dabscheck, E ; De Souza, J ; Downing, M ; Feinstein, A ; Ferentinos, PP ; Flint, AJ ; Gallagher, P ; Gandy, M ; Grassi, L ; Haerter, M ; Hernando, A ; Jackson, ML ; Jenewein, J ; Jette, N ; Juliao, M ; Kjaergaard, M ; Kohler, S ; Konig, H-H ; Krishna, LKR ; Lee, Y ; Loebner, M ; Loosman, WL ; Love, AW ; Loewe, B ; Malt, UF ; Marrie, RA ; Massardo, L ; Matsuoka, Y ; Mehnert, A ; Michopoulos, I ; Misery, L ; Nelson, CJ ; Ng, CG ; O'Donnell, ML ; O'Rourke, SJ ; Ozturk, A ; Pabst, A ; Pasco, JA ; Peceliuniene, J ; Pintor, L ; Ponsford, JL ; Pulido, F ; Quinn, TJ ; Reme, SE ; Reuter, K ; Riedel-Heller, SG ; Rooney, AG ; Sanchez-Gonzalez, R ; Saracino, RM ; Schellekens, MPJ ; Scherer, M ; Schwarzbold, ML ; Cankorur, VS ; Sharpe, L ; Sharpe, M ; Simard, S ; Singer, S ; Stafford, L ; Stone, J ; Strobe, NA ; Sultan, S ; Teixeira, AL ; Tiringer, I ; Turner, A ; Walker, J ; Walterfang, M ; Wang, L-J ; Weyerer, SB ; White, J ; Wiese, B ; Williams, LJ ; Wong, L-Y ; Benedetti, A ; Thombsi, BD (AMER PSYCHOLOGICAL ASSOC, 2023-02)
    The seven-item Hospital Anxiety and Depression Scale Depression subscale (HADS-D) and the total score of the 14-item HADS (HADS-T) are both used for major depression screening. Compared to the HADS-D, the HADS-T includes anxiety items and requires more time to complete. We compared the screening accuracy of the HADS-D and HADS-T for major depression detection. We conducted an individual participant data meta-analysis and fit bivariate random effects models to assess diagnostic accuracy among participants with both HADS-D and HADS-T scores. We identified optimal cutoffs, estimated sensitivity and specificity with 95% confidence intervals, and compared screening accuracy across paired cutoffs via two-stage and individual-level models. We used a 0.05 equivalence margin to assess equivalency in sensitivity and specificity. 20,700 participants (2,285 major depression cases) from 98 studies were included. Cutoffs of ≥7 for the HADS-D (sensitivity 0.79 [0.75, 0.83], specificity 0.78 [0.75, 0.80]) and ≥15 for the HADS-T (sensitivity 0.79 [0.76, 0.82], specificity 0.81 [0.78, 0.83]) minimized the distance to the top-left corner of the receiver operating characteristic curve. Across all sets of paired cutoffs evaluated, differences of sensitivity between HADS-T and HADS-D ranged from -0.05 to 0.01 (0.00 at paired optimal cutoffs), and differences of specificity were within 0.03 for all cutoffs (0.02-0.03). The pattern was similar among outpatients, although the HADS-T was slightly (not nonequivalently) more specific among inpatients. The accuracy of HADS-T was equivalent to the HADS-D for detecting major depression. In most settings, the shorter HADS-D would be preferred. (PsycInfo Database Record (c) 2023 APA, all rights reserved).
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    Changes in body composition in the year following critical illness: A case-control study
    Thackeray, M ; Kotowicz, MA ; Pasco, JA ; Mohebbi, M ; Orford, N (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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    Bipolar disorder and bone health: A case-control study
    Williams, LJ ; Stuart, AL ; Berk, M ; Brennan-Olsen, SL ; Hodge, JM ; Quirk, SE ; Koivumaa-Honkanen, H ; Honkanen, R ; Heikkinen, J ; Chandrasekaran, V ; Cleminson, JR ; Pasco, JA (ELSEVIER, 2022-07-01)
    BACKGROUND: Bipolar disorder (BD) is associated with significant psychological and physical comorbidity. Yet little is known about the bone health of individuals with BD. Thus, we aimed to investigate the association between BD and bone health in a population-based sample of women. METHODS: Women with a history of BD (cases; n = 117) were recruited from public and private health care settings and controls, without BD, were drawn from the Geelong Osteoporosis Study (n = 909). BD was identified using a semi-structured clinical interview (SCID-I/NP). Bone mineral density (BMD) was measured at the spine, femoral neck and total body using dual energy x-ray absorptiometry, and bone quality by quantitative heel ultrasound and included the following parameters: Speed of Sound (SOS), Broadband Ultrasound Attenuation (BUA) and Stiffness Index (SI). Weight and height were measured and information on medication use and lifestyle was obtained. RESULTS: Adjusted mean BMD among the cases was 4.3% lower at the hip and 1.6% lower at the total body compared to controls. Age was an effect modifier at the spine. Among women <50 years, mean spine BMD for cases was 3.5% lower than controls. No differences in spine BMD for those ≥50 years were detected. Cases also had a 1.0%, 3.2% and 7.8% lower adjusted mean SOS, BUA and SI compared to controls, respectively. LIMITATIONS: Course, chronicity and recovery of BD were not explored in relation to bone health. CONCLUSION: These data suggest BD is associated with low bone quantity and quality in women. Replication and research into underlying mechanisms is warranted.
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    Associations between parameters of peripheral quantitative computed tomography and bone material strength index
    Holloway-Kew, KL ; Rufus-Membere, P ; Anderson, KB ; Tembo, MC ; Sui, SX ; Hyde, NK ; Diez-Perez, A ; Kotowicz, MA ; Pasco, JA (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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    Estimation of Whole-Body and Appendicular Lean Mass from Spine and Hip Dual Energy X-ray Absorptiometry: A Cross-Sectional Study
    Thackeray, M ; Orford, NR ; Kotowicz, MA ; Mohebbi, M ; Pasco, JA (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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    Lipopolysaccharide-binding protein and bone health: data from a population-based sample of men
    Cleminson, JR ; Pasco, JA ; Bortolasci, CC ; Holloway-Kew, KL ; Hodge, JM ; Anderson, KB ; Kotowicz, MA ; Samarasinghe, RM ; Williams, LJ (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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    Peripheral quantitative computed tomography-derived bone parameters in men with impaired fasting glucose and diabetes
    Holloway-Kew, KL ; Anderson, KB ; Tembo, MC ; Sui, SX ; Harland, JW ; Hyde, NK ; Kotowicz, MA ; Pasco, JA (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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    Clinical Utility of Thigh and Mid-Thigh Dual-Energy x-Ray Absorptiometry to Identify Bone and Muscle Loss
    Vogrin, S ; Hassan, EB ; Putra, FM ; Pasco, JA ; Kotowicz, MA ; Duque, G (WILEY, 2023-04)