Long-Term Implications of Socioeconomic Status on Major Adverse Cardiovascular, Cerebrovascular Events (MACCE), and All-Cause Mortality.

BACKGROUND: Socio-economic status (SES) has a large impact on health through a complex interplay of upstream, midstream and downstream factors. However, little is known about the predictive role of SES on long-term major adverse cardiovascular, cerebrovascular events, and mortality (MACCE). AIM: To determine the long-term relationship between SES and MACCE for men and women. The secondary endpoint was to determine the relationship between SES and all-cause mortality. METHOD: A total of 3,034 participants (1,494 women and 1,540 men) were assessed at baseline in the Geelong Osteoporosis Study, a large regional Australian population cohort study. Area-based SES was assessed, utilising the Index of Relative Socio-Economic Disadvantage (IRSD) and grouped into quintiles. The primary endpoint, MACCE, was defined as a composite of myocardial infarction, heart failure hospitalisation, malignant arrhythmias, stroke, and all-cause mortality. The secondary endpoint was all-cause mortality. Baseline data including age, sex, smoking status and alcohol use, and comorbidities were collected between 1993-1997 for women, and 2001-2006 for men, with follow-up over 30 and 22 years, respectively. Logistic regression was utilised to assess MACCE and all-cause mortality outcomes across the SES quintiles. RESULTS: Participants lost to follow-up or with incomplete data collection were excluded leaving 2,173 participants eligible for analysis. SES was associated with MACCE outcomes. Compared with Quintile I (lowest SES stratum), the odds of MACCE for each IRSD stratum were: Quintile II, odds ratio (OR) 0.85 (95% confidence interval [CI] 0.65-1.13); Quintile III, OR 0.69 (95% CI 0.51-0.91); Quintile IV, OR 0.66 (95% CI 0.50-0.88); and, Quintile V, OR 0.55 (95% CI 0.41-0.72). In the adjusted model, an inverse trend was noted, with reducing MACCE outcomes with an increasing SES status; IRSD Quintile II, OR 0.85 (95% CI 0.62-1.17); Quintile III, OR 0.70 (95% CI 0.50-0.97); Quintile IV, OR 0.73 (95% CI 0.52-1.02); and, Quintile V, OR 0.54 (95% CI 0.39-0.74). SES was inversely associated with all-cause mortality; IRSD Quintile II (OR 0.87, 95% CI 0.66-1.16) failed to achieve significance however IRSD Quintile III (OR 0.65, 95% CI 0.48-0.88), Quintile IV (OR 0.59, 95% CI 0.44-0.80) and Quintile V (OR 0.46, 95% CI 0.34-0.62) had a lower risk of mortality compared with Quintile I. In the adjusted model, an inversely proportional trend was noted between SES and all-cause mortality; IRSD Quintile II (OR 0.82, 95% CI 0.59-1.15), IRSD Quintile III (OR 0.63, 95% CI 0.49-0.95), Quintile IV (OR 0.59, 95% CI 0.45-0.90) and Quintile V (OR 0.44, 95% CI 0.31-0.61) had fewer mortality events compared with IRSD Quintile I. CONCLUSIONS: Our research indicates that being part of a lower socio-economic stratum is linked to a higher likelihood of experiencing negative cardiovascular and cerebrovascular events, along with an increased risk of overall mortality. SES is an important risk stratification marker for long-term prognosis of cardiovascular diseases and stroke, and warrants further investigation.

Psychiatric symptoms, associated pharmacological treatments and cognitive function: A population-based study of men.

BACKGROUND: Psychiatric symptomatology and medications used in their treatment may be modifiable risk factors associated with cognitive function, although findings from population-based studies spanning the full adult age range are lacking. This study aimed to investigate associations between psychiatric symptomatology, psychotropic medication use and cognitive function in a population-based sample of men. METHODS: Data for 537 men were drawn from the Geelong Osteoporosis Study. Cognitive function (psychomotor function, attention, working memory and visual learning) was determined using the Cog-State Brief Battery. Current depressive and anxiety symptomatology was determined using the Hospital Anxiety and Depression Scale, and psychotropic medication use was self-reported. Linear regression models were developed to determine associations between psychiatric symptomatology and psychotropic medication use with each cognitive measure. RESULTS: Depressive symptomatology was associated with lower overall cognitive function (b-0.037 ± 0.010, η2 = 0.025, p < 0.001), psychomotor function (b 0.006 ± 0.002, η2 = 0.028 p < 0.001) and attention (b 0.004 ± 0.001, η2 = 0.021, p < 0.001), whereas psychotropic use was associated with lower overall cognitive function (b - 0.174 ± 0.075, η2 = 0.010, p = 0.021), attention (b 0.017 ± 0.008, η2 = 0.008, p = 0.038 and working memory (b 0.031 ± 0.012, η2 = 0.010, p = 0.010). Anticonvulsant use was associated with lower overall cognitive function (b - 0.723 ± 0.172, η2 = 0.032, p < 0.001), attention (b 0.065 ± 0.018, η2 = 0.029, p < 0.001) and working memory (b 0.088 ± 0.026, η2 = 0.022, p < 0.001). All relationships were found to have a small effect. There were no significant associations between anxiety symptomatology and antidepressant and anxiolytic use with any of the cognitive domains. CONCLUSION: Depressive symptomatology and anticonvulsant use were associated with lower cognitive function. Understanding the underlying mechanisms involved in these relationships can advance knowledge on the heterogeneity in cognitive ageing and aid in prevention initiatives.

Emergency presentations for farm-related injuries in older adults residing in south-western Victoria, Australia.

INTRODUCTION: Farm workers are at high risk for injuries, and epidemiological data are needed to plan resource allocation. OBJECTIVE: This study identified regions with high farm-related injury rates in the Barwon South West region of Victoria, Australia, for residents aged ≥50 yr. DESIGN: Retrospective synthesis using electronic medical records of emergency presentations occurring during 2017-2019 inclusive for Local Government Areas (LGA) in the study region. For each LGA, age-standardised incidence rates (per 1000 population/year) were calculated. FINDINGS: For men and women combined, there were 31 218 emergency presentations for any injury, and 1150 (3.68%) of these were farm-related. The overall age-standardised rate for farm-related injury presentations was 2.6 (95% CI 2.4-2.7); men had a higher rate than women (4.1, 95% CI 3.9-4.4 versus 1.2, 95% CI 1.0-1.3, respectively). For individual LGAs, the highest rates of farm-related emergency presentations occurred in Moyne and Southern Grampians, both rural LGAs. Approximately two-thirds of farm-related injuries occurred during work activities (65.0%), and most individuals arrived at the hospital by transport classified as "other" (including private car, 83.3%). There were also several common injury causes identified: "other animal related injury" (20.2%), "cutting, piercing object" (19.5%), "fall ⟨1 m" (13.1%), and "struck by or collision with object" (12.5%). Few injuries were caused by machinery (1.7%) and these occurred mainly in the LGA of Moyne (65%). DISCUSSION AND CONCLUSION: This study provides data to inform future research and resource allocation for the prevention of farm-related injuries.

Associations between ultra-distal forearm bone mineral density and incident fracture in women.

Bone mineral density measured at the ultra-distal forearm site was associated with any fracture, as well as distal radius fracture in women from a longitudinal cohort study. PURPOSE: Femoral neck (BMDhip) and lumbar spine (BMDspine) bone mineral density (BMD) are routinely used to assess fracture risk. More data are needed to understand how ultra-distal forearm BMD (BMDUDforearm) may assist fracture prediction. METHODS: Using a Lunar DPX-L, Geelong Osteoporosis Study women (n = 1026), aged 40-90 years, had BMD measured. Incident low-trauma fractures were radiologically verified. Using Cox proportional hazard models, hazard ratios (HR) were calculated for BMDUDforearm as a continuous variable (expressed as a one-unit decrease in T-score) and a categorical variable (normal/osteopenia/osteoporosis). Areas under receiver operating characteristics (AUROC) curves were calculated. Analyses were conducted for any fracture and distal radius fractures. RESULTS: During 14,270 person-years of follow-up, there were 318 fractures (85 distal radius). In adjusted models, continuous BMDUDforearm was associated with any (HR 1.26;95%CI 1.15-1.39) and distal radius fractures (HR 1.59;95%CI 1.38-1.83). AUROCs for continuous BMDUDforearm, 33% forearm(BMD33%forearm), BMDhip, BMDspine, and FRAX without BMD were similar for any fracture (p > 0.05). For distal radius fracture, the AUROC for BMDUDforearm was higher than other sites and FRAX (p < 0.05). In adjusted models, those with osteoporosis had a higher likelihood of any fracture (HR 2.12; 95%CI 1.50-2.98). For distal radius fractures, both osteopenia and osteoporosis had a higher risk (HR 4.31; 95%CI 2.59-7.15 and 4.81; 95%CI 2.70-8.58). AUROCs for any fracture were similar for categorical BMD at all sites but lower for FRAX (p < 0.05). For distal radius fractures, the AUROC for BMDUDforearm, was higher than other sites and FRAX (p < 0.05). CONCLUSION: Ultra-distal forearm BMD may aid risk assessments for any distal radius fractures.

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

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

Health service and medication costs associated with common mental disorders and subthreshold symptoms in women: Findings from the Geelong Osteoporosis Study in Australia.

OBJECTIVE: This analysis estimated 2013 annual healthcare costs associated with the common mental disorders of mood and anxiety disorders and psychological symptoms within a representative sample of Australian women. METHODS: Data from the 15-year follow-up of women in the Geelong Osteoporosis Study were linked to 12-month Medicare Benefits Schedule and Pharmaceutical Benefits Scheme data. A Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Non-patient edition identified common mental disorders and the General Health Questionnaire 12 assessed psychological symptoms. Participants were categorised into mutually exclusive groups: (1) common mental disorder (past 12 months), (2) subthreshold (no common mental disorder and General Health Questionnaire 12 score ⩾4) or (3) no common mental disorder and General Health Questionnaire 12 score <4. Two-part and hurdle models estimated differences in service use, and adjusted generalised linear models estimated mean differences in costs between groups. RESULTS: Compared to no common mental disorder, women with common mental disorders utilised more Medicare Benefits Schedule services (mean 26.9 vs 20.0, p < 0.001), had higher total Medicare Benefits Schedule cost ($1889 vs $1305, p < 0.01), received more Pharmaceutical Benefits Scheme prescriptions (35.8 vs 20.6, p < 0.001), had higher total Pharmaceutical Benefits Scheme cost ($1226 vs $740, p < 0.05) and had significantly higher annual out-of-pocket costs for Pharmaceutical Benefits Scheme prescriptions ($249 vs $162, p < 0.001). Compared to no common mental disorder, subthreshold women were less likely to use any Medicare Benefits Schedule service (89.6% vs 97.0%, p < 0.01), but more likely to use mental health services (11.4% vs 2.9%, p < 0.01). The subthreshold group received more Pharmaceutical Benefits Scheme prescriptions (mean 43.3 vs 20.6, p < 0.001) and incurred higher total Pharmaceutical Benefits Scheme cost ($1268 vs $740, p < .05) compared to no common mental disorder. CONCLUSIONS: Common mental disorders and subthreshold psychological symptoms place a substantial economic burden on Australian healthcare services and consumers.

The practicality of using bone impact microindentation in a population-based study of women: A Geelong-Osteoporosis Study.

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.

Lithium use and bone health in women with bipolar disorder: A cross-sectional study.

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.

A pilot feasibility randomised controlled trial of bone antiresorptive agents on bone turnover markers in critically ill women.

Critical illness is associated with increased bone turnover, loss of bone density, and increased risk of fragility fractures. The impact of bone antiresorptive agents in this population is not established. This trial examined the efficacy, feasibility, and safety of antiresorptive agents administered to critically ill women aged fifty years or greater. Women aged 50 years or greater admitted to an intensive care unit for at least 24 h were randomised to receive an antiresorptive agent (zoledronic acid or denosumab) or placebo, during critical illness and six months later (denosumab only). Bone turnover markers and bone mineral density (BMD) were monitored for 1 year. We studied 18 patients over 35 months before stopping the study due to the COVID-19 pandemic. Antiresorptive medications decreased the bone turnover marker type 1 cross-linked c-telopeptide (CTX) from day 0 to 28 by 43% (± 40%), compared to an increase of 26% (± 55%) observed with placebo (absolute difference - 69%, 95% CI - 127% to - 11%), p = 0.03). Mixed linear modelling revealed differences in the month after trial drug administration between the groups in serum CTX, alkaline phosphatase, parathyroid hormone, and phosphate. Change in BMD between antiresorptive and placebo groups was not statistically analysed due to small numbers. No serious adverse events were recorded. In critically ill women aged 50-years and over, antiresorptive agents suppressed bone resorption markers without serious adverse events. However, recruitment was slow. Further phase 2 trials examining the efficacy of these agents are warranted and should address barriers to enrolment.Trial registration: ACTRN12617000545369, registered 18th April 2017.

Femora of women with premature ovarian insufficiency exhibit reduced strength and misalignment with the transmitted vertical forces from the upper body.

BACKGROUND: Women with premature ovarian insufficiency (POI) lack oestrogen, which is a key determinant of bone growth, epiphyseal closure, and bone tissue organisation. Although dual-energy X-ray absorptiometry (DXA)-derived areal bone mineral density (BMD) remains the gold standard for fracture risk evaluation, it does not fully characterise the skeletal abnormalities present in these women. Hence, we aimed to assess hip/femur anatomy, strength, and geometry and femoral alignment using advanced hip analysis (AHA). METHODS: We conducted a cross-sectional, case-control study including 89 women with spontaneous normal karyotype POI (s-POI) or iatrogenic POI (i-POI), aged 20-50 years compared with 89 age- and body mass index (BMI)-matched population-based female controls. Hip anatomy, strength, geometrical parameters, and femur alignment were measured using hip DXA images and Lunar AHA software. Femoral orientation angle (FOA) was quantified as the overall orientation of the femur with respect to the axis of the forces transmitted from the upper body. RESULTS: The median age of POI diagnosis was 35 (18-40) years; the mean POI duration at the time of DXA was 2.07 (range 0-13) years, and 84% of POI women received oestrogen therapy. Areal BMD at all sites was significantly lower in the POI group (all P < .05). Indices of compressive and bending strength were lower in women with POI compared with controls, specifically the cross-sectional area (CSA, mm2) and section modulus (SM, mm3) (139.30 ± 29.08 vs 157.29 ± 22.26, P < .001 and 665.21 ± 129.54 vs 575.53 ± 150.88, P < .001, respectively). The FOA was smaller (124.99 ± 3.18) in women with POI as compared with controls (128.04 ± 3.80; P < .001) at baseline and after adjusting for height and femoral neck BMD. CONCLUSION: Alongside lower BMD at multiple sites, the femora of women with POI demonstrate reduced strength and a misalignment with forces transmitted from the upper body. Further research is needed to establish the role of these newly identified features and their role in fracture risk prediction in this population.

Quality of life in south-eastern Australia: normative values for the WHOQOL-BREF in a population-based sample of adults.

OBJECTIVES: The abbreviated World Health Organisation Quality of Life tool (WHOQOL-BREF) is a short-form quality of life (QoL) assessment commonly used worldwide in both healthy and ill populations. Normative data for the Australian general population are limited. The objective of this study was to present normative data for the WHOQOL-BREF based on a general population sample. A secondary aim was to explore sociodemographic factors related to QoL. DESIGN: Population-based cross-sectional study. PARTICIPANTS: 929 men and 830 women aged 24-94 years participating in the Geelong Osteoporosis Study. OUTCOME MEASURES: The 26-item WHOQOL-BREF. RESULTS: Means and SD for each domain are presented by age group and sex. Percentile scores were also generated. Mean scores for WHOQOL-BREF domains were 74.52 (SD=16.22) for physical health, 72.07 (SD=15.35) for psychological, 72.87 (SD=18.78) for social relationships and 79.68 (SD=12.55) for environment. We identified significant associations between sociodemographic factors and WHOQOL-BREF domains. Notably, being married or in a relationship was associated with increased odds for high QoL across all four WHOQOL-BREF domains: physical health (women OR 2.46, 95% CI 1.36 to 4.44, p=0.003), psychological (men OR 2.07, 95% CI: 1.20 to 3.55, p=0.009; women OR 2.15, 95% CI 1.21 to 3.81, p=0.009), social relationships (men OR 2.28, 95% CI 1.29 to 4.04, p=0.005; women OR 2.77, 95% CI 1.42 to 5.41, p=0.003) and environment (women OR 2.07, 95% CI 1.13 to 3.80, p=0.019). CONCLUSIONS: This study provides population norms for the WHOQOL-BREF based on a representative sample of Australian adults. Our results will be useful to researchers and clinicians who can use these data as a reference point for interpreting WHOQOL-BREF scores.

For older individuals there is greater variance in low mean Bone Material Strength Index values obtained with the OsteoProbe.

Purpose: Bone Material Strength Index (BMSi) quantifies the resistance of bone to a specified force in vivo at the mid tibia using impact microindentation (IMI). Anecdotal evidence suggests that within-participant variance in BMSi may be associated with the individual's mean BMSi. This study aimed to investigate associations between mean and variance of IMI measures in a population-based study. Methods: Participants were men (n = 420) and women (n = 55) from the Geelong Osteoporosis Study who underwent BMSi measurement using the OsteoProbe at recent follow-up phases (men 2016-2022; women 2022-2023). Median age was 63.7 yr (IQR 53.0-71.8). BMSi standard deviation was skewed and therefore natural log transformed (referred to as ln-SD). Linear regression models were developed with ln-SD as the dependent variable and mean BMSi as the independent variable adjusting for sex, age, height and weight. Results: In unadjusted models, greater BMSi was associated with lower ln-SD (ß = -1.58, p = 0.042). This association was sustained after adjustment (p = 0.013), and an interaction between BMSi and age was observed (p = 0.004). In those aged 63.7 yr and over (median age), mean BMSi was inversely associated with ln-SD (ß = -3.22, p = 0.002). Sex was not identified as an effect modifier. In younger participants, no BMSi*ln-SD association was observed. Conclusion: In older men and women, there was greater variance in low BMSi values. This suggests that standard deviation of the BMSi measure may provide additional information in the assessment of bone health and is worthy of further investigation. Mini abstract: In older men and women, greater variance is observed when BMSi values are low, reflecting potential variation in the bone surface.

Negative back beliefs are associated with increased odds of low back pain and disability: a 10-year cohort study in men.

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.

Impact of Mood Disorder History and Bone Health on Cognitive Function Among Men Without Dementia.

BACKGROUND: Poor cognitive function, a major disabling condition of older age, is often considered a prodromal feature of dementia. High mortality and the lack of a cure for dementia have necessitated a focus on the identification of potentially modifiable risk factors. Mental and physical health conditions such as mood disorders and bone loss have been previously linked with poor cognition individually although their combined effect remains largely unknown. OBJECTIVE: Considering the multifactorial nature of dementia pathology, we investigated whether mood disorders, bone health and their interaction are associated with cognitive function in a population-based sample of men. METHODS: Four hundred and forty-two male participants were drawn from the Geelong Osteoporosis Study. Cognitive function was assessed using the CogState Brief Battery, which measured cognitive performance across four domains and was used to compute overall cognitive function. Mood disorders and hip bone mineral density (BMD) were determined using a semi-structured clinical interview and dual-energy X-ray absorptiometry, respectively. RESULTS: Hip BMD (Bcoeff = 0.56, 95% CI: [0.07, 1.05], p = 0.025) but not mood disorder (Bcoeff = -0.50, 95% CI: [-0.20, 0.10], p = 0.529) was associated with overall cognitive function after accounting for potential confounders. Interaction effects were observed between the two exposures (Bcoeff = -1.37, 95% CI: [-2.49, -0.26], p = 0.016) suggesting that individuals without a mood disorder displayed better cognitive performance with increasing BMD, while those with a lifetime history of mood disorder displayed poorer cognitive function with increasing BMD. CONCLUSIONS: These findings highlight the importance of exploring interactions among potentially modifiable health conditions associated with cognitive function.

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

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

Mean Bone Material Strength Index Values for Women are Lower Than Those for Men: Data from a Single Geographical Location.

Bone material strength index (BMSi) values are obtained using impact microindentation, which assesses the ability of bone to resist indentation. Differences in BMSi between men and women are unclear, and to date, BMSi sex differences have not been compared for individuals from the same population. Therefore, we compared BMSi values for men and women drawn from the same geographical location in Australia. Participants (n = 220) were from the Geelong Osteoporosis Study. BMSi was measured, following international published guidelines, using an OsteoProbe for participants at recent follow-up phases (women 2022-2023 and men 2016-2022). Women (n = 55) were age matched to men (n = 165) in a 1:3 ratio. A two-sample t test was used to determine the intergroup difference in mean BMSi. Linear regression was also performed, adjusting for weight and height. Median (IQR) ages for men and women were 67.0 (61.7-71.5) and 67.4 (62.0-71.2) years (p = 0.998). Men were heavier (81.0 ± 10.9 vs 71.0 ± 13.9 kg, p < 0.001) and taller (173.9 ± 6.4 vs 161.5 ± 7.5 cm, p < 0.001) than women. Mean (± SD) BMSi for women (75.7 ± 7.4) was lower than for men (82.8 ± 6.8) (p < 0.001). The difference persisted after adjustment for weight and height (mean ± SE: 76.5 ± 1.1 vs 82.5 ± 0.6, p < 0.001). Given the higher fracture risk observed for women, the higher mean BMSi values in men are consistent with cross sectional data suggesting this measure may be useful in fracture prediction.

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

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

A plasma protein signature associated with cognitive function in men without severe cognitive impairment.

BACKGROUND: A minimally invasive blood-based assessment of cognitive function could be a promising screening strategy to identify high-risk groups for the incidence of Alzheimer's disease. METHODS: The study included 448 cognitively unimpaired men (mean age 64.1 years) drawn from the Geelong Osteoporosis Study. A targeted mass spectrometry-based proteomic assay was performed to measure the abundance levels of 269 plasma proteins followed by linear regression analyses adjusted for age and APOE ε4 carrier status to identify the biomarkers related to overall cognitive function. Furthermore, two-way interactions were conducted to see whether Alzheimer's disease-linked genetic variants or health conditions modify the association between biomarkers and cognitive function. RESULTS: Ten plasma proteins showed an association with overall cognitive function. This association was modified by allelic variants in genes ABCA7, CLU, BDNF and MS4A6A that have been previously linked to Alzheimer's disease. Modifiable health conditions such as mood disorders and poor bone health, which are postulated to be risk factors for Alzheimer's disease, also impacted the relationship observed between protein marker levels and cognition. In addition to the univariate analyses, an 11-feature multianalyte model was created using the least absolute shrinkage and selection operator regression that identified 10 protein features and age associated with cognitive function. CONCLUSIONS: Overall, the present study revealed plasma protein candidates that may contribute to the development of a blood-based screening test for identifying early cognitive changes. This study also highlights the importance of considering other risk factors in elucidating the relationship between biomarkers and cognition, an area that remains largely unexplored.

Biofabrication of functional bone tissue: defining tissue-engineered scaffolds from nature.

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.