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INTRODUCTION: Several psychiatric disorders and medications used to treat them appear to be independently associated with skeletal deficits. As there is increasing evidence that lithium possesses skeletal protective properties, we aimed to investigate the association between lithium use and bone health in a group of women with bipolar disorder. METHOD: Women with bipolar disorder (n = 117, 20+ years) were recruited from south-eastern Australia. Bipolar disorder was confirmed using a clinical interview (SCID-I/NP). Bone mineral density (BMD; g/cm2 ) was measured at the spine, hip and total body using dual-energy x-ray absorptiometry and low bone mass determined by BMD T-score of <-1.0. Weight and height were measured, socioeconomic status (SES) determined and information on medication use and lifestyle factors self-reported. Linear and logistic regression were used to test associations between lithium and (i) BMD and (ii) low bone mass, respectively. RESULTS: Thirty-five (29.9%) women reported current lithium use. Lithium users and non-users differed in regard to SES and BMD; otherwise, groups were similar. After adjustments, mean BMD among lithium users was 5.1% greater at the spine (1.275 [95% CI 1.229-1.321] vs. 1.214 [1.183-1.244] g/cm2 , p = 0.03), 4.2% greater at the total hip (0.979 [0.942-1.016] vs. 0.938 [0.910-0.966] g/cm2 , p = 0.03) and 2.2% greater at the total body (1.176 [1.148-1.205] vs. 1.150 [1.129-1.171] g/cm2 , p = 0.08) compared to participants not receiving lithium. Lithium users were also less likely to have low bone mass (22.9% vs. 43.9%, p = 0.031). Associations persisted after adjustment for confounders. CONCLUSION: These data suggest lithium is associated with greater BMD and reduced risk of low bone mass in women with bipolar disorder. Research into the underlying mechanisms is warranted.

UNLABELLED: The relationship between self-reported falls and fracture risk was estimated in an international meta-analysis of individual-level data from 46 prospective cohorts. Previous falls were associated with an increased fracture risk in women and men and should be considered as an additional risk factor in the FRAX® algorithm. INTRODUCTION: Previous falls are a well-documented risk factor for subsequent fracture but have not yet been incorporated into the FRAX algorithm. The aim of this study was to evaluate, in an international meta-analysis, the association between previous falls and subsequent fracture risk and its relation to sex, age, duration of follow-up, and bone mineral density (BMD). METHODS: The resource comprised 906,359 women and men (66.9% female) from 46 prospective cohorts. Previous falls were uniformly defined as any fall occurring during the previous year in 43 cohorts; the remaining three cohorts had a different question construct. The association between previous falls and fracture risk (any clinical fracture, osteoporotic fracture, major osteoporotic fracture, and hip fracture) was examined using an extension of the Poisson regression model in each cohort and each sex, followed by random-effects meta-analyses of the weighted beta coefficients. RESULTS: Falls in the past year were reported in 21.4% of individuals. During a follow-up of 9,102,207 person-years, 87,352 fractures occurred of which 19,509 were hip fractures. A previous fall was associated with a significantly increased risk of any clinical fracture both in women (hazard ratio (HR) 1.42, 95% confidence interval (CI) 1.33-1.51) and men (HR 1.53, 95% CI 1.41-1.67). The HRs were of similar magnitude for osteoporotic, major osteoporotic fracture, and hip fracture. Sex significantly modified the association between previous fall and fracture risk, with predictive values being higher in men than in women (e.g., for major osteoporotic fracture, HR 1.53 (95% CI 1.27-1.84) in men vs. HR 1

Impact microindentation (IMI) is a minimally invasive technique that allows the assessment of bone material strength index (BMSi) in vivo, by measuring the depth of a micron-sized, spherical tip into cortical bone that is then indexed to the depth of the tip into a reference material. In this study, we aimed to assess the practicality of its application in 99 women aged 42-84 yr from the Geelong Osteoporosis Study. Impact microindentation was performed in the mid-shaft of the right tibia using the OsteoProbe. Immediately following measurement, each participant was requested to rate on a Visual Analogue Scale [0-10] the level of discomfort anticipated and experienced, any initial reluctance towards the measurement and whether they were willing to repeat the measurement. Of 99 potential participants who attended this assessment phase, 55 underwent IMI measurement. Reasons for non-measurement in 44 women were existing skin conditions (n = 8, 18.2 %) and excessive soft tissue around mid-tibial region (n = 32, 72.2 %). An additional four (9.1 %) participants did not provide any reasons for declining. For 55 participants who had underwent IMI, the expectation for pain when briefed about the procedure was low (2.28 ± 2.39), as was pain experienced during the measurement (0.72 ± 1.58). Participants were not reluctant to undergo the measurement (0.83 ± 1.67), and all indicated a willingness to repeat the measurement. Results of this study showed that the IMI technique is well tolerated and accepted by women participating in the Geelong Osteoporosis Study, suggesting that the technique shows promise in a research or clinical setting.

INTRODUCTION: Mood disorders are a major cause of disability, and current treatment options are inadequate for reducing the burden on a global scale. The aim of this project was to identify drugs suitable for repurposing to treat mood disorders. METHODS: This mixed-method study utilized gene expression signature technology and pharmacoepidemiology to investigate drugs that may be suitable for repurposing to treat mood disorders. RESULTS: The transcriptional effects of a combination of drugs commonly used to treat mood disorders included regulation of the steroid and terpenoid backbone biosynthesis pathways, suggesting a mechanism involving cholesterol biosynthesis, and effects on the thyroid hormone signaling pathway. Connectivity Map analysis highlighted metformin, an FDA-approved treatment for type 2 diabetes, as a drug having global transcriptional effects similar to the mood disorder drug combination investigated. In a retrospective cohort study, we found evidence that metformin is protective against the onset of mood disorders. DISCUSSION: These results provide proof-of-principle of combining gene expression signature technology with pharmacoepidemiology to identify potential novel drugs for treating mood disorders. Importantly, metformin may have utility in the treatment of mood disorders, warranting future randomized controlled trials to test its efficacy.

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.

OBJECTIVE: Although negative back beliefs are associated with high-intensity low back pain (LBP)/disability, whether they influence incident high-intensity LBP/high-disability over the long-term is unknown. This study aimed to investigate whether negative back beliefs were associated with developing high-intensity LBP and/or high-disability over 10 years in men. METHODS: Men with no or low-intensity LBP and/or disability attending the Geelong Osteoporosis Study between 2006-2010 were included. Data on age, body mass index, mobility, education, back beliefs (Back Beliefs Questionnaire), LBP and disability (Graded Chronic Pain Scale) were collected between 2006-2010. Beliefs, LBP and disability were re-assessed in 2016-2021. Binary logistic regression was used to examine the association between negative back beliefs and incident high-intensity pain and/or high-disability, adjusting for age, body mass index, mobility, and education. RESULTS: At baseline, 705 participants (mean age 53.8 years) had no or low LBP and no or low-disability; 441 (62.6%) participants completed a 10-year follow-up. Of these, 37 (8.4%) developed high-intensity pain and/or high-disability. In multivariate analyses, participants with more negative back beliefs at baseline were more likely to develop high-intensity pain and/or high-disability (Odds ratio 1.05, 95% CI 1.00-1.11). Developing more negative back beliefs was also associated with incident high-intensity pain and/or high-disability (Odds Ratio 1.20, 95% CI 1.12-1.30). CONCLUSION: In a male community-based population, negative beliefs regarding the consequences of LBP were associated with an increased likelihood of developing high-intensity pain and/or high-disability. Addressing negative back beliefs in the community may reduce the incidence of high-intensity pain and/or high-disability over 10 years in men.

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.

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).

BACKGROUND: Sarcopenia is an age-associated skeletal muscle condition characterized by low muscle mass, strength, and physical performance. There is no international consensus on a sarcopenia definition and no contemporaneous clinical and research guidelines specific to Australia and New Zealand. The Australian and New Zealand Society for Sarcopenia and Frailty Research (ANZSSFR) Sarcopenia Diagnosis and Management Task Force aimed to develop consensus guidelines for sarcopenia prevention, assessment, management and research, informed by evidence, consumer opinion, and expert consensus, for use by health professionals and researchers in Australia and New Zealand. METHODS: A four-phase modified Delphi process involving topic experts and informed by consumers, was undertaken between July 2020 and August 2021. Phase 1 involved a structured meeting of 29 Task Force members and a systematic literature search from which the Phase 2 online survey was developed (Qualtrics). Topic experts responded to 18 statements, using 11-point Likert scales with agreement threshold set a priori at >80%, and five multiple-choice questions. Statements with moderate agreement (70%-80%) were revised and re-introduced in Phase 3, and statements with low agreement (<70%) were rejected. In Phase 3, topic experts responded to six revised statements and three additional questions, incorporating results from a parallel Consumer Expert Delphi study. Phase 4 involved finalization of consensus statements. RESULTS: Topic experts from Australia (n = 62, 92.5%) and New Zealand (n = 5, 7.5%) with a mean ± SD age of 45.7 ± 11.8 years participated in Phase 2; 38 (56.7%) were women, 38 (56.7%) were health professionals and 27 (40.3%) were researchers/academics. In Phase 2, 15 of 18 (83.3%) statements on sarcopenia prevention, screening, assessment, management and future research were accepted with strong agreement. The strongest agreement related to encouraging a healthy lifestyle (100%) and offering tailor

Impact microindentation (IMI) is a novel technique for assessing bone material strength index (BMSi) in vivo, by measuring the depth of a micron-sized, spherical tip into cortical bone that is then indexed to the depth of the tip into a reference material. The aim of this study was to define the reference intervals for men and women by evaluating healthy adults from the United States of America, Europe and Australia. Participants included community-based volunteers and participants drawn from clinical and population-based studies. BMSi was measured on the tibial diaphysis using an OsteoProbe in 479 healthy adults (197 male and 282 female, ages 25 to 98 years) across seven research centres, between 2011 and 2018. Associations between BMSi, age, sex and areal bone mineral density (BMD) were examined following an a posteriori method. Unitless BMSi values ranged from 48 to 101. The mean (± standard deviation) BMSi for men was 84.4 ± 6.9 and for women, 79.0 ± 9.1. Healthy reference intervals for BMSi were identified as 71.0 to 97.9 for men and 59.8 to 95.2 for women. This study provides healthy reference data that can be used to calculate T- and Z-scores for BMSi and assist in determining the utility of BMSi in fracture prediction. These data will be useful for positioning individuals within the population and for identifying those with BMSi at the extremes of the population.

Damage to bone leads to pain and loss of movement in the musculoskeletal system. Although bone can regenerate, sometimes it is damaged beyond its innate capacity. Research interest is increasingly turning to tissue engineering (TE) processes to provide a clinical solution for bone defects. Despite the increasing biomimicry of tissue-engineered scaffolds, significant gaps remain in creating the complex bone substitutes, which include the biochemical and physical conditions required to recapitulate bone cells' natural growth, differentiation and maturation. Combining advanced biomaterials with new additive manufacturing technologies allows the development of 3D tissue, capable of forming cell aggregates and organoids based on natural and stimulated cues. Here, we provide an overview of the structure and mechanical properties of natural bone, the role of bone cells, the remodelling process, cytokines and signalling pathways, causes of bone defects and typical treatments and new TE strategies. We highlight processes of selecting biomaterials, cells and growth factors. Finally, we discuss innovative tissue-engineered models that have physiological and anatomical relevance for cancer treatments, injectable stimuli gels, and other therapeutic drug delivery systems. We also review current challenges and prospects of bone TE. Overall, this review serves as guide to understand and develop better tissue-engineered bone designs.

BACKGROUND: Falls are a common occurrence in psychiatric hospital settings, however population-based research among individuals with psychiatric disorders, in particular bipolar disorder (BD) is scant. Thus, we aimed to investigate falls risk in community-dwelling women diagnosed with BD. METHODS: Women with BD (cases, n = 119) were recruited from health care settings located in southeast Victoria, Australia. Age-matched controls (n = 357, ratio 3:1) without BD were participants in the Geelong Osteoporosis Study drawn from the same geographical region. Lifetime history of BD was identified by semi-structured clinical interview (SCID-IV/NP). Previous 12-month falls data were obtained via questionnaire. Information on mobility, alcohol use, general health, medication use, blood pressure, body mass index, socioeconomic status and use of a walking aid was collected. Generalised Estimating Equations, binary and ordinal logistic regression were used to determine the odds ratio (OR) and 95% confidence interval (CI) for falls following adjustment for confounders. RESULTS: During the 12-month period, 34 (28.6%, median age 48.4 yr) cases and 70 (19.6%, median age 49.1 yr) controls reported one fall; 22 (18.5%) cases and 18 (5.0%) controls reported ≥ two falls (p < 0.001). Cases had 2.5-fold increased odds of at least one fall and 2.9-fold increased likelihood of increasing falls categories (0 vs. 1 vs. 2 +), compared to controls [adjOR 2.5, 95%CI (1.8, 3.4), adjOR OR 2.9, 95%CI (2.0, 4.1)]. CONCLUSION: Risk of falls was greater among women with BD. Balance training could be a research and clinical focus for falls prevention programs among women with bipolar disorder to prevent the detrimental outcomes associated with falling.

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.

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.

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.

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.

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.

Medications used to treat hypertension may affect fracture risk. This study investigated fracture risk for users of angiotensin converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARB). Participants (899 men, median age 70.3 yr (59.9-79.1), range 50.0-96.6 yr; 574 women, median age 65.5 yr (58.1-75.4), range 50.1-94.6 yr) were from the Geelong Osteoporosis Study. Medication use was self-reported and incident fractures were ascertained using radiological reports. Bone mineral density (BMD) was measured at the femoral neck. Participants were divided into four groups: (1) non-users without hypertension, (2) non-users with hypertension, (3) ACEI users and (4) ARB users. Dosage was calculated using the defined daily dose (DDD) criteria. Participants were followed from date of visit to first fracture, death or 31 December 2016, whichever occurred first. Cox proportional hazards models were used for analyses. At least one incident fracture was sustained by 156 men and 135 women over a median(IQR) of 11.5(6.2-13.2) and 10.9(6.3-11.6) years of follow-up, respectively. In unadjusted analyses, compared to non-users without hypertension, men in all three other groups had a higher risk of fracture (Hazard Ratio (HR, 95%CI) 1.54, 1.00-2.37; 1.90, 1.18-3.05; 2.15, 1.26-3.66), for non-users with hypertension, ACEI and ARB users, respectively). Following adjustment for age, prior fracture and BMD, these associations became non-significant. A dose effect for ARB use was observed; men using lower doses had a higher risk of fracture than non-users without hypertension, in both unadjusted (2.66, 1.34-5.29) and adjusted (2.03, 1.01-4.08) analyses, but this association was not observed at higher doses. For women, unadjusted analyses showed a higher risk for ACEI users compared to non-users without hypertension (1.74, 1.07-2.83). This was explained after adjustment for age, alcohol consumption, prior fracture and BMD (1.28, 0.74-2.22). No other differences were observe

BACKGROUND: Beta-casein is a major protein in cow's milk, of which A1 and A2 are the most frequent variants. Recent evidence implicates A1 beta-casein consumption in mechanisms that are of potential importance to mental health, yet its possible effects on psychological endpoints remains unknown. The primary aim of the study is to evaluate the comparative effects of consumption of dairy products containing A2 beta-casein versus conventional dairy (i.e. containing both A1 and A2 beta-casein) on symptoms of psychological distress in women with low mood. METHODS: 'The Moo'D Study' is a 16-week, superiority, 1:1 parallel group, triple-blinded, randomised controlled trial. Ninety women with low mood (Patient Health Questionnaire score ≥ 5) will be randomised to consume either A2 beta-casein only or conventional dairy products. The primary outcome, symptoms of psychological distress, will be measured by the 21-item Depression, Anxiety and Stress Scale. Secondary outcomes will include symptoms of depression, anxiety and stress, severity of low mood, cognition, gut microbiota composition, gut symptomatology, markers of immune function, gut inflammation, systemic metabolites, endothelial integrity and oxidative stress, body composition, perceived wellbeing, sleep, quality of life, resource use and cost-effectiveness. DISCUSSION: This study will advance our understanding of the possible impact of milk proteins on psychological distress in women as well as elucidate mechanisms underpinning any association. Given dairy products form a substantial component of traditional and Western diets, the implications of these findings are likely to be of clinical and public health importance. TRIAL REGISTRATION: The trial protocol has been prospectively registered with the Australia and New Zealand Clinical Trials Registry, ACTRN12618002023235 . Registered on 17 December 2018.

BACKGROUND: Musculoskeletal conditions and physical frailty have overlapping constructs. We aimed to quantify individual contributions of musculoskeletal factors to frailty. METHODS: Participants included 347 men and 360 women aged ≥60 yr (median ages; 70.8 (66.1-78.6) and 71.0 (65.2-77.5), respectively) from the Geelong Osteoporosis Study. Frailty was defined as ≥3, pre-frail 1-2, and robust 0, of the following; unintentional weight loss, weakness, low physical activity, exhaustion, and slowness. Measures were made of femoral neck BMD, appendicular lean mass index (ALMI, kg/m2) and whole-body fat mass index (FMI, kg/m2) by DXA (Lunar), SOS, BUA and SI at the calcaneus (Lunar Achilles Insight) and handgrip strength by dynamometers. Binary and ordinal logistic regression models and AUROC curves were used to quantify the contribution of musculoskeletal parameters to frailty. Potential confounders included anthropometry, smoking, alcohol, prior fracture, FMI, SES and comorbidities. RESULTS: Overall, 54(15.6%) men and 62(17.2%) women were frail. In adjusted-binary logistic models, SI, ALMI and HGS were associated with frailty in men (OR = 0.73, 95%CI 0.53-1.01; OR=0.48, 0.34-0.68; and OR = 0.11, 0.06-0.22; respectively). Muscle measures (ALMI and HGS) contributed more to this association than did bone (SI) (AUROCs 0.77, 0.85 vs 0.71, respectively). In women, only HGS was associated with frailty in adjusted models (OR = 0.30 95%CI 0.20-0.45, AUROC = 0.83). In adjusted ordinal models, similar results were observed in men; for women, HGS and ALMI were associated with frailty (ordered OR = 0.30 95%CI 0.20-0.45; OR = 0.56, 0.40-0.80, respectively). CONCLUSION: Muscle deficits appeared to contribute more than bone deficits to frailty. This may have implications for identifying potential musculoskeletal targets for preventing or managing the progression of frailty.

Background Originally, sarcopenia meant ‘poverty of flesh’, but recent operational definitions have brought poor muscle function to the fore. None has considered psychological well‐being. We compared muscle function components of the European Working Group on Sarcopenia in Older People Version 2 (EWGSOP2), the Foundation for the National Institutes of Health (FNIH), and the Sarcopenia Definitions and Outcomes Consortium (SDOC) algorithms for individuals with and without depressive and anxiety symptoms. Methods This cross‐sectional study involved 348 women and 343 men (ages 60–96 years) from the Geelong Osteoporosis Study. Hospital Anxiety and Depression Scale scores for depression and anxiety ≥8 indicated depressive and anxiety symptoms. Measures included handgrip strength (HGS) and Timed Up and Go (TUG). Chi‐squared test identified inter‐group differences, and multivariable logistic regression identified poor muscle function in association with depressive or anxiety symptoms. Results Twenty‐nine (8.3%) women and 28 (8.2%) men had depressive symptoms, and 83 (23.9%) women and 41 (12.0%) men had anxiety symptoms. For women, proportions with low HGS were greater for those with vs. without depressive symptoms according to EWGSOP2 and FNIH (37.9% vs. 10.7%) and SDOC (51.7% vs. 26.7%); low HGS/body mass index (44.8% vs. 15.7%); and slow TUG (12.5% vs. 1.4%) (all P ≤ 0.011). In age‐adjusted models, women with depressive symptoms were two‐fold to five‐fold more likely to have low HGS by EWGSOP2 and FNIH {odds ratio [OR] 4.77 [95% confidence interval (CI) 1.83–12.45]} and SDOC [OR 2.59 (95% CI 1.10–6.07)], low HGS/body mass index [OR 3.92 (95% CI 1.69–9.07)], and 11‐fold more likely to have a slow TUG [OR 10.99 (95% CI 2.03–59.7)]. For men, a difference for low HGS for those with depressive symptoms was detected only for SDOC (64.3% vs. 40.0%, P = 0.013), but this was explained by age [OR 1.99 (95% CI 0.84–4.71)]. No differences were detected for anxiety symptoms.

BACKGROUND: Anticonvulsant use has been linked to bone deficits in specific patient populations. We studied the association between anticonvulsant use and bone health in a population-based sample of men and women. METHODS: Data from 926 men (24-73 yr) and 1070 women (21-94 yr) participating in the Geelong Osteoporosis Study were included. Bone mineral density (BMD, g/cm2) of the PA-spine and total hip was measured using dual-energy X-ray absorptiometry (Lunar). Bone quality was determined using quantitative heel ultrasound (QUS). Anthropometry was conducted and socioeconomic status was determined. Medication and lifestyle information was obtained via questionnaire. Linear regression was used to test associations between anticonvulsant use and bone health before and after adjustment for potential confounders. RESULTS: Seventeen (1.8%) men and 20 (1.9%) women reported anticonvulsant use. In men, anticonvulsant users had 9.1% lower adjusted mean BMD at the spine and hip compared to non-users. Body mass index was an effect modifier at the spine. Anticonvulsant users also had 1.8% lower speed of sound (SOS), 10.6% lower broadband ultrasound attenuation (BUA) and 13.7% lower stiffness index (SI) compared to non-users. In women, BMD tended to be lower at the hip compared to non-users as with the bone quality measure, BUA. No significant associations were observed at the spine or the other bone quality measures, SOS and SI. CONCLUSION: Our data suggest that bone quantity and quality, assessed using BMD and QUS, are lower for men and possibly women who use anticonvulsants. While further exploration into potential mechanisms is needed, our findings suggest that monitoring bone health among users of anticonvulsants is warranted.

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 dif

OBJECTIVE: The role of mood disorders in cancer onset is unclear. The aim of this study was to investigate the association between mood disorder and incident cancer in a population-based sample of women. METHODS: Data were derived from women aged 28-94 years participating in the Geelong Osteoporosis Study. Mood disorder was identified via Clinical Interview (SCID-I/NP). Cancer data was obtained following linkage with the Victorian Cancer Registry. Demographic and lifestyle factors were self-reported. Nested case-control and retrospective study designs were utilized. RESULTS: In the case-control study (n=807), mood disorder was documented for 18 of the 75 (9.3%) cancer cases and among 288 controls (24.0% vs. 39.3%, p = 0.009). Prior exposure to mood disorder was associated with reduced cancer incidence (OR 0.49, 95%CI 0.28-0.84); this was sustained following adjustment for confounders (ORadj 0.52, 95%CI 0.30-0.90). In the retrospective cohort study (n=655), among 154 women with a history of mood disorder at baseline, 13 (8.5%) developed incident cancer during follow-up, whereas among 501 women with no history of mood disorder, 54 (10.8%) developed incident cancer. Exposure to mood disorder was not associated with incident cancer over the follow-up period (HR 0.58, 95%CI 0.31-1.08, p = 0.09). CONCLUSION: Mood disorder was associated with reduced odds of cancer onset. However, this finding was not supported in the retrospective cohort study. Larger studies able to investigate specific cancers and mood disorders as well as underlying mechanisms in both men and women are warranted.

OBJECTIVES: The health and well-being of older women may be influenced by frailty and low socioeconomic status (SES). This study examined the association between frailty and SES, healthcare utilisation and quality of life (QOL) among older women in regional Australia. METHODS: Cross-sectional analysis of the Geelong Osteoporosis Study was conducted on 360 women (ages ≥60yr) in the 15-year follow up. Frailty was identified using modified Fried's phenotype. Individual SES measures and healthcare utilisation were documented by questionnaire. Area-based SES was determined by cross-referencing residential addresses with the Australian Bureau of Statistics Index of Relative Socio-economic Advantage and Disadvantage (IRSAD). QOL was measured using the Australian World Health Organisation Quality of Life Instrument (WHOQoL-Bref). Multinomial logistic regression was conducted with frailty groupings as outcome. RESULTS: Sixty-two (17.2%) participants were frail, 199 (55.3%) pre-frail and 99 (27.5%) robust. Frail participants were older with higher body mass index. Frailty was associated with lower education but not marital status, occupation or IRSAD. Strong associations with frailty were demonstrated for all WHOQoL-Bref domains. Frailty was associated with more primary care doctor visits (p<0.001). CONCLUSIONS: This population-based study highlights the significant impact of frailty on older women, indicating reduced QOL and increased primary care doctor visits.

OBJECTIVES: To develop guidelines, informed by health-care consumer values and preferences, for sarcopenia prevention, assessment and management for use by clinicians and researchers in Australia and New Zealand. METHODS: A three-phase Consumer Expert Delphi process was undertaken between July 2020 and August 2021. Consumer experts included adults with lived experience of sarcopenia or health-care utilisation. Phase 1 involved a structured meeting of the Australian and New Zealand Society for Sarcopenia and Frailty Research (ANZSSFR) Sarcopenia Diagnosis and Management Task Force and consumer representatives from which the Phase 2 survey was developed. In Phase 2, consumers from Australia and New Zealand were surveyed online with opinions sought on sarcopenia outcome priorities, consultation preferences and interventions. Findings were confirmed and disseminated in Phase 3. Descriptive statistical analyses were performed. RESULTS: Twenty-four consumers (mean ± standard deviation age 67.5 ± 12.8 years, 18 women) participated in Phase 2. Ten (42%) identified as being interested in sarcopenia, 7 (29%) were health-care consumers and 6 (25%) self-reported having/believing they have sarcopenia. Consumers identified physical performance, living circumstances, morale, quality of life and social connectedness as the most important outcomes related to sarcopenia. Consumers either had no preference (46%) or preferred their doctor (40%) to diagnose sarcopenia and preferred to undergo assessments at least yearly (54%). For prevention and treatment, 46% of consumers preferred resistance exercise, 2-3 times per week (54%). CONCLUSIONS: Consumer preferences reported in this study can inform the implementation of sarcopenia guidelines into clinical practice at local, state and national levels across Australia and New Zealand.

Stroke is a leading cause of death and disability and is responsible for a significant economic burden. Sarcopenia and cognitive dysfunction are common consequences of stroke, but there is less awareness of the concurrency of these conditions. In addition, few reviews are available to guide clinicians and researchers on how to approach sarcopenia and cognitive dysfunction as comorbidities after stroke, including how to assess and manage them and implement interventions to improve health outcomes. This review synthesises current knowledge about the relationship between post-stroke sarcopenia and cognitive dysfunction, including the physiological pathways, assessment tools, and interventions involved.

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.

Low muscle mass is associated with reduced independence and increased risk for falls and fractures. Identification of modifiable risk factors for low muscle mass is thus imperative. This study aimed to examine the longitudinal relationship between both diet quality and patterns and lean mass in Australian women. Data from n = 494 participants of the Geelong Osteoporosis Study's 10- and 15-year women's follow-ups were used (conducted in 2004-08 and 2011-14, respectively), and participants were aged 21-89 years. Self-reported lifestyle and demographics were collected, and food frequency questionnaire data informed the dietary exposure variables: the Australian Recommended Food Score (ARFS); the Dietary Inflammatory Index (DII); and a posteriori dietary patterns. The outcome, Skeletal Muscle Index (SMI), was calculated from DXA-derived appendicular lean mass (ALM) relative to height (ALM kg/m2). Analyses employed Generalised Estimating Equations. A higher ARFS score positively predicted SMI over 5-years, and adjustments for age and physical activity did not attenuate this relationship (B:0.044, (95%CI 0.004, 0.084) kg/m2). Following adjustment, both an anti-inflammatory diet (B:-0.034, (95%CI -0.070, -0.002) kg/m2) and a 'traditional' dietary pattern predicted higher SMI (B:0.081, (95%CI 0.004, 0.158) kg/m2). No other associations were observed. Our study reinforces the importance of diet quality for healthy, aging muscle mass. Furthermore, a less inflammatory diet and a diet comprising a wide variety of plant and animal foods may be conducive to maintenance of muscle mass in women. Further studies investigating diet quality's impact on various muscle health measures over longer time periods are warranted.

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 bon

OBJECTIVES: We aimed to investigate fracture risk associated with anticonvulsant use in a population-based sample of men and women. METHODS: Data from 1,458 participants (51.8% women) with a radiologically confirmed incident fracture (cases) were compared to 1,796 participants (46.5% women) without fracture (controls). Lifestyle factors, medication use and medical history were self-reported. Associations between anticonvulsant use and fracture were explored using binary logistic regression following adjustment for confounders. RESULTS: In men, fracture cases and controls differed in age, smoking history, education, alcohol use, and gonadal hormone supplementation. In women, fracture cases and controls differed by previous fracture history, alcohol use, physical activity levels and use of anti-fracture agents. After adjustment for age, pooled anticonvulsant use was associated with a 3.4-fold higher risk of fracture in men and a 1.8-fold higher risk in women. Following further adjustments for confounders these patterns persisted; a 2.8-fold higher fracture risk in men and a 1.8-fold higher fracture risk in women. CONCLUSIONS: Anticonvulsant use was associated with increased fracture risk, independent of demographic, lifestyle, medical and medication related factors. While further studies exploring potential underlying mechanisms are warranted, regular monitoring of bone health in anticonvulsant users with risk factors may be useful.

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.

Background: Falls are a significant cause of injuries, loss of confidence, increased morbidity, and institutionalisation in all older people, with women at 50% greater risk than men. The relationship between dementia and falls is well established and 2/3 of all dementia occurs in women. In this study we explored risk factors associated with a 14 year falls risk in a community-based cohort of women, which included validated measures across a wide range of clinical domains including neuropsychological, mood, quality of life and biomarkers (including hormonal). Method: The Australian Women’s Healthy Aging Project is an longitudinal observation study, assessments every year (1991 –1999), followed by assessments in 2002, 2004, 2012 and 2014. The assessments included cognitive (as of 2002), blood, and cardiovascular disease risk assessment, and questions related to falls. After data cleaning, the remaining cohort consisted of 180 participants (Table 1). Missing data were imputed using mice random forest. To identify key risk factors associated with a 14 year falls risk, random survival (time to event) forest (RSF) machine learning was used. Result: The RSF model, using all 290+ possible predictive variables, performed well with an Out Of Bag (OOB, withheld data) prediction error (C-index) of 32.8%. The most predictive variables in the model were identified using the variable importance measure (VIM). The initial model was refined by taking the top 30 predictive variables and retraining the RSF. This refined model resulted in an improved OOB C-index of 5.8% (27%). The top 20 predictive variables, Figure 1, include those associated with cardiovascular disease risk, cognitive performance, and hormone levels (e.g., family history of heart attack, digit symbol coding, and estradiol levels). Conclusion: Ninety percent of the top 20 predictive risk variables for the 14 year fall risk in women, were from three key domains, cognition (40%), cardiovascular (25%) and hormone-related

We aimed to examine muscle strength, function and mass in relation to cognition in older men. This cross-sectional data-set included 292 men aged ≥60 yr. Handgrip strength (kg) was measured by dynamometry, gait speed by 4-metre walk (m/s) and appendicular lean mass (kg) by dual-energy x-ray absorptiometry. Cognition was assessed across four domains: psychomotor function, attention, visual learning and working memory. Composite scores for overall cognition were calculated. Bivariate analyses indicated that handgrip strength and gait speed were positively associated with cognitive function. After accounting for confounders, positive associations between individual muscle (or physical) measures and cognitive performance were sustained for handgrip strength and psychomotor function, gait speed and psychomotor function, gait speed and attention, handgrip strength and overall cognition, and gait speed and overall cognition. In multivariable models, handgrip strength and gait speed independently predicted psychomotor function and overall cognition. No associations were detected between lean mass and cognition after adjusting for confounders. Thus, low muscle strength and slower gait speed, rather than low lean mass, were associated with poor cognition in older men.

BACKGROUND: Low handgrip strength (HGS) is a measure of poor skeletal muscle performance and a marker of ill health and frailty. Muscle quality (MQ) is a measure of muscle strength relative to muscle mass. We aimed to develop normative data for HGS and MQ, report age-related prevalence of low HGS and MQ, and determine the relationship with age, anthropometry, and body composition for women in Australia. METHODS: This cross-sectional analysis included data from 792 women (ages 28-95 years) assessed by the Geelong Osteoporosis Study. Duplicate measures of HGS were performed for each hand with a dynamometer (Jamar) and the mean of maximum values used for analyses. Dual energy X-ray absorptiometry-derived lean mass for the arms was used to calculate MQ as HGS/lean mass (kg/kg). Body mass index (BMI) was categorized as normal (BMI < 25.0 kg/m2 ), overweight (25.0-29.9 kg/m2 ), and obese (>30.0 kg/m2 ). Fat mass index (FMI) was calculated as whole body fat/height2 (kg/m2 ) and appendicular lean mass index (ALMI) as lean mass of arms and legs/height2 (kg/m2 ). RESULTS: Mean (±SD) of HGS values for normal BMI, overweight, and obese groups were 25 (±7), 24 (±7), and 24 (±7) kg, P = 0.09, and for MQ, 12 (±3), 11 (±3), and 10 (±3) kg/kg, P < 0.001. Our data indicated a quadratic relationship between age and HGS or MQ. Mean HGS and MQ remained stable until the fifth age decade then declined steadily with increasing age; therefore, we used data for women (n = 283) aged 28-49 years as the young adult reference group, with mean (SD) values for HGS 28 (±6) kg and MQ 12 (±3) kg/kg. The prevalence of low (T-score < -2) HGS and MQ for women 80 years and older was 52.2% and 39.6%, respectively. In multivariable models, age-adjusted HGS was associated with FMI (B = -0.13, P = 0.004) and ALMI (1.03, <0.001) while age-adjusted MQ was associated with BMI (-0.15, <0.001) but not with FMI. In a sensitivity analysis, the same pattern remained after the removal of 129 women who reported hand a

The effects of dairy and dairy-derived products on the human gut microbiota remains understudied. A systematic literature search was conducted using Medline, CINAHL, Embase, Scopus, and PubMed databases with the aim of collating evidence on the intakes of all types of dairy and their effects on the gut microbiota in adults. Risk of bias was assessed using the Cochrane risk-of-bias tool.The search resulted in 6,592 studies, of which eight randomized controlled trials (RCTs) met pre-determined eligibility criteria for inclusion, consisting of a total of 468 participants. Seven studies assessed the effect of type of dairy (milk, yogurt, and kefir) and dairy derivatives (whey and casein) on the gut microbiota, and one study assessed the effect of the quantity of dairy (high dairy vs low dairy). Three studies showed that dairy types consumed (milk, yogurt, and kefir) increased the abundance of beneficial genera Lactobacillus and Bifidobacterium. One study showed that yogurt reduced the abundance of Bacteroides fragilis, a pathogenic strain. Whey and casein isolates and the quantity of dairy consumed did not prompt changes to the gut microbiota composition. All but one study reported no changes to bacterial diversity in response to dairy interventions and one study reported reduction in bacterial diversity in response to milk intake.In conclusion, the results of this review suggest that dairy products such as milk, yogurt, and kefir may modulate the gut microbiota composition in favor to the host. However, the broader health implications of these findings remain unclear and warrant further studies.

Dementia comprises a wide range of progressive and acquired neurocognitive disorders. Obesity, defined as excessive body fat tissue, is a common health issue world-wide and a risk factor for dementia. The adverse effects of obesity on the brain and the central nervous system have been the subject of considerable research. The aim of this review is to explore the available evidence in the field of body-brain crosstalk focusing on obesity and brain function, to identify the major research measurements and methodologies used in the field, to discuss the potential risk factors and biological mechanisms, and to identify the research gap as a precursor to systematic reviews and empirical studies in more focused topics related to the obesity-brain relationship. To conclude, obesity appears to be associated with reduced brain function. However, obesity is a complex health condition, while the human brain is the most complicated organ, so research in this area is difficult. Inconsistency in definitions and measurement techniques detract from the literature on brain-body relationships. Advanced techniques developed in recent years are capable of improving investigations of this relationship.

We examined whether personality disorders (PDs) (any, cluster A/B/C) were associated with bone mineral density (BMD) in a population-based sample of Australian women (n = 696). Personality and mood disorders were assessed using semi-structured diagnostic interviews. BMD was measured at the spine, hip, and total body using dual-energy x-ray absorptiometry (GE-Lunar Prodigy). Anthropometrics, medication use, physical conditions, and lifestyle factors were documented. The association between PDs (any, cluster A/B/C) and BMD (spine/hip/total body) was examined with multiple linear regression models. The best models were identified by backward elimination including age, weight, physical activity, smoking status, alcohol consumption, dietary calcium intake, mood disorders, physical multimorbidity, socioeconomic status, and medications affecting bone. The variables were retained in the model if p < 0.05. All potential interactions in final models were tested. Those with cluster A PD, compared to those without, had 6.7% lower hip BMD [age, weight adjusted mean 0.853 (95% CI 0.803-0.903) vs. 0.910 (95% CI 0.901-0.919) g/cm2, p = 0.027] and 3.4% lower total body BMD [age, weight, smoking, alcohol, calcium adjusted mean 1.102 (95% CI 1.064-1.140) vs. 1.139 (95% CI 1.128-1.150) g/cm2, p = 0.056]. No associations were observed between cluster B/C PDs and hip/total body BMD or between any of the PD clusters and spine BMD. To our knowledge, this study is the first to investigate the bone health of women with PD in a population-based sample. Given the paucity of literature, replication and longitudinal research including the examination of underlying mechanisms and sex differences are warranted.

BACKGROUND: The extent of muscle deterioration associated with ageing or disease can be quantified by comparison with appropriate reference data. The objective of this study is to present normative data for lower-limb muscle strength and quality for 573 males and 923 females aged 20-97 yr participating in the Geelong Osteoporosis Study in southeastern Australia. METHODS: In this cross-sectional study, measures of muscle strength for hip flexors and hip abductors were obtained using a Nicholas manual muscle tester, a hand-held dynamometer (HHD; kg). Leg lean mass was measured by dual energy x-ray absorptiometry (DXA; kg), and muscle quality calculated as strength/mass (N/kg). RESULTS: For both sexes, muscle strength and quality decreased with advancing age. Age explained 12.9-25.3% of the variance in muscle strength in males, and 20.8-24.6% in females; age explained less of the variance in muscle quality. Means and standard deviations for muscle strength and quality for each muscle group are reported by age-decade for each sex, and cutpoints equivalent to T-scores of - 2.0 and - 1.0 were derived using data from young males (n = 89) and females (n = 148) aged 20-39 years. CONCLUSIONS: These data will be useful for quantifying the extent of dynapenia and poor muscle quality among adults in the general population in the face of frailty, sarcopenia and other age-related muscle dysfunction.

BACKGROUND: Frailty is characterised by age-related declines in physical, psychological and social functioning. Features of frailty overlap with risk factors for fragility fractures. The aim of this study was to investigate the association between the fracture risk assessment tool (FRAX®) and frailty. METHODS: In cross-sectional analysis, frailty status was determined for participants aged 60-90 yr at 15-year follow-up of the Geelong Osteoporosis Study, using a modified Fried frailty phenotype. Using the FRAX on-line tool, scores for hip and major osteoporotic fracture (MOF) were calculated with and without bone mineral density (BMD). Using the area under Receiver Operating Characteristic (AUROC) curves, and FRAX scores calculated at the baseline visit for these participants, we investigated the association of FRAX and frailty 15 years later. RESULTS: Forty-seven of 303 women (15.5%) and 41 of 282 men (14.5%) were frail at the 15-year visit. There was a gradient of increasing median FRAX scores from robust to frail. For example, for women, median MOF-FRAX without BMD increased from 5.9 for the robust to 7.5 for the pre-frail and 14.0 for the frail (p < 0.001). In secondary analyses, an association was observed between FRAX and frailty over 15 years, with the highest AUROC for women being 0.72 for MOF-FRAX with BMD, and for men, 0.76 hip-FRAX without BMD. CONCLUSION: An association was observed between FRAX and frailty where frail men and women had higher FRAX-scores compared to the other groups. Preliminary data suggest that FRAX, with or without BMD, may be useful in enhancing the information on frailty. Further research using larger datasets will be required to explore this.

INTRODUCTION: Individuals with schizophrenia are known to be at higher risk of comorbid conditions, both physical and psychological. Osteoporosis is possibly one of these, leading to public health concerns due to higher rates of associated mortality and morbidity. We aim to systematically search all available evidence across electronic databases regarding the relationship between schizophrenia and bone fragility. METHODS AND ANALYSIS: A systematic search of the research databases CINAHL, MEDLINE Complete, Embase and PsycINFO will be conducted and identified papers reviewed for eligibility, with a second reviewer confirming inclusions. Searches will be run from database inception to 1 October 2020 and supplemented by the hand checking of references of identified articles. A previously published scoring system will be used for assessing the methodological quality and risk of bias. A meta-analysis is planned. ETHICS AND DISSEMINATION: Due to including published literature only, ethical permission will not be necessary. Results of this study will be published in a relevant scientific journal and presented at a conference in the field of interest. PROSPERO REGISTRATION NUMBER: CRD42020171959.

Frailty, a clinical syndrome characterized by multisystem dysregulation, has been associated with high levels of oxidative stress. We investigated the association between serum total antioxidant capacity (TAC) and frailty in older men. This cross-sectional study included 581 men (age 60-90 years) enrolled in the Geelong Osteoporosis Study. Frailty comprised at least three of unintentional weight loss, exhaustion, low physical activity, slowness, and weakness. Serum TAC was measured by quantitative colorimetric determination and expressed as uric acid equivalents (mM). Relationships between TAC (in SD units) and frailty were explored using multivariable logistic regression models. Sociodemographic, anthropometric, and lifestyle variables were tested as potential confounders and effect modifiers. A sensitivity analysis excluded participants (n = 145) in the upper quartile of TAC, who were likely to have hyperuricemia. Fifty (8.6%) men were frail. There was evidence that higher TAC levels were associated with increased likelihood of frailty (OR 1.34, 95% confidence interval [CI; 0.99, 1.80]), and this was attenuated after adjustment for age and body mass index (BMI; OR 1.26, 95% CI [0.93,1.71]). No effect modifiers or other confounders were identified. The sensitivity analysis revealed a positive association between TAC and frailty, before and after accounting for age and BMI (adjusted OR 1.79, 95% CI [1.01, 3.17] p = .038). These results suggest a positive association between TAC levels and frailty, supporting the hypothesis that this biomarker could be useful in identifying individuals at risk of frailty. We speculate that a milieu of heightened oxidative stress in frailty may elevate the oxidative stress regulatory set point, raising antioxidant activity. This warrants further investigation.

PURPOSE: The Vitamin D in Pregnancy Study is a long-term ongoing cohort study. It was conceived to explore relationships between maternal vitamin D status in pregnancy and offspring growth and development, and has since diversified to include a wide range of physical and mental health exposures and outcomes. PARTICIPANTS: Recruitment was from the University Hospital Geelong (Barwon Health) antenatal clinic, Geelong, Victoria, Australia, between 2002 and 2004. 475 women were initially recruited, which resulted in 400 eligible mother-child pairs at birth. FINDINGS TO DATE: The cohort has been followed up twice in pregnancy, at birth, and 1 year, 6 years and 11 years post birth. The study has reported an association between vitamin D in pregnancy and musculoskeletal health and body composition in the children. FUTURE PLANS: Subject to funding, there will be a prospective young adult follow-up. This profile aims to foster both cross-national and international collaborations with both existing and future data collection.

INTRODUCTION: Little is known about the bone health of adults with bipolar disorder, aside from evidence purporting bone deficits among individuals with other mental illnesses, or those taking medications commonly used in bipolar disorder. In this paper, we present the methodology of a case-control study which aims to examine the role of bipolar disorder as a risk factor for bone fragility. METHODS AND ANALYSIS: Men and women with bipolar disorder (~200 cases) will be recruited and compared with participants with no history of bipolar disorder (~1500 controls) from the Geelong Osteoporosis Study. Both cases and controls will be drawn from the Barwon Statistical Division, south-eastern Australia. The Structured Clinical Interview for DSM-IV-TR Research Version, Non-patient edition is the primary diagnostic instrument, and psychiatric symptomatology will be assessed using validated rating scales. Demographic information and detailed lifestyle data and medical history will be collected via comprehensive questionnaires. Participants will undergo dual energy X-ray absorptiometry scans and other clinical measures to determine bone and body composition. Blood samples will be provided after an overnight fast and stored for batch analysis. ETHICS AND DISSEMINATION: Ethics approval has been granted from Barwon Health Research Ethics Committee. Participation in the study is voluntary. The study findings will be disseminated via peer-reviewed publications, conference presentations and reports to the funding body.

Objective There are currently five widely used definition of prediabetes. We compared the ability of these to predict 5-year conversion to diabetes and investigated whether there were other cut-points identifying risk of progression to diabetes that may be more useful. Research design and methods We conducted an individual participant meta-analysis using longitudinal data included in the Obesity, Diabetes and Cardiovascular Disease Collaboration. Cox regression models were used to obtain study-specific HRs for incident diabetes associated with each prediabetes definition. Harrell's C-statistics were used to estimate how well each prediabetes definition discriminated 5-year risk of diabetes. Spline and receiver operating characteristic curve (ROC) analyses were used to identify alternative cut-points. Results Sixteen studies, with 76 513 participants and 8208 incident diabetes cases, were available. Compared with normoglycemia, current prediabetes definitions were associated with four to eight times higher diabetes risk (HRs (95% CIs): 3.78 (3.11 to 4.60) to 8.36 (4.88 to 14.33)) and all definitions discriminated 5-year diabetes risk with good accuracy (C-statistics 0.79-0.81). Cut-points identified through spline analysis were fasting plasma glucose (FPG) 5.1 mmol/L and glycated hemoglobin (HbA1c) 5.0% (31 mmol/mol) and cut-points identified through ROC analysis were FPG 5.6 mmol/L, 2-hour postload glucose 7.0 mmol/L and HbA1c 5.6% (38 mmol/mol). Conclusions In terms of identifying individuals at greatest risk of developing diabetes within 5 years, using prediabetes definitions that have lower values produced non-significant gain. Therefore, deciding which definition to use will ultimately depend on the goal for identifying individuals at risk of diabetes.