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Hip structural analysis parameters are associated with risk of fracture in women across a long follow-up period, with buckling ratio persisting independent of total hip BMD., Purpose: Hip structural analysis (HSA) uses dual X-ray absorptiometry (DXA) hip scans to calculate geometries of narrow neck (NN), intertrochanter (IT), and shaft (S), which may complement bone mineral density (BMD) for assessing fracture risk. We aimed to determine whether HSA parameters were associated with fracture., Methods: Participants were women (n = 986, ages 40-94 year) from the Geelong Osteoporosis Study. HSA was calculated from Lunar DPX-L scans. Low-trauma incident fractures were identified radiologically. Participants were followed from baseline to first fracture, death, or end of follow-up period (31/12/16) (13,487 person-years follow-up). Time-updating Cox-proportional hazards modelling investigated associations between HSA parameters and fracture., Results: Three hundred thirty-five participants reported fractures (rate: 24.99/1000 person-years [95% CI 22.46-27.80]). Higher NN BMD (HR:0.12, 95% CI:0.05-0.29), cross-sectional area (CSA) (0.37, 0.26-0.52), cross-sectional moment of inertia (CSMI) (0.66, 0.50-0.89), section modulus (SM) (0.40, 0.24-0.68) and cortical thickness (CT) (0.00, 0.00-0.01 due to rounding) were associated with decreased risk. IT BMD (0.08, 0.04-0.20), CSA (0.58, 0.49-0.69), CSMI (0.90, 0.85-0.94), and SM (0.69, 0.59-0.81) were similarly associated. Decreased risk was observed at increased values of S BMD (0.20, 0.10-0.38), CSA (0.60, 0.47-0.76), SM (0.60, 0.43-0.83), and CT (0.03, 0.01-0.14). Higher S endocortical diameter (1.81, 1.29-2.53), and buckling ratio (BR) at all sites (NN: 1.07, 1.04-1.11; IT: 1.08, 1.05-1.11, S: 1.31, 1.19-1.46) were associated with increased risk. After adjustment for total hip BMD, the associations with BR at the shaft (1.14, 1.00-1.30) were sustained. Other associations were attenuated., Conclusion: A greater shaft buckling ratio was associated with an increased risk for fracture, independent of total hip BMD., (© 2024. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

Background: Falls are a significant public health challenge, especially among older adults. In Australia, falls and related injuries incur an annual cost of $2.3 billion. However, there is a scarcity of prevalence data on falls among population-based groups. This study aimed to report the characteristics, circumstances, and treatment for falls and fall-related injuries in a population-based sample of Australian men and women., Methods: Participants from the Geelong Osteoporosis Study provided cross-sectional data: baseline for men (2001-2006) and 10-year follow-up for women (2004-2008). Falls over the previous 12 months were self-reported by 2,631 participants aged 20-97 years (1,533 men and 1,098 women). The study described the timing, location, cause, and treatment of falls. Fall prevalence was standardized to the 2006 Australian population. Data collection included self-reported prior fractures, medication, disease conditions, anthropometry, and biochemical tests. Binary logistic regression identified factors linked to fall-related injuries., Results: Fall rates by age group: 20-29 (24.4%), 30-39 (21.5%), 40-49 (18.7%), 50-59 (24.9%), 60-69 (25.0%), 70-79 (34.6%), 80+ (40.5%). The age-standardized prevalence of falls was 25.0% (95% CI: 23.4-26.7%). In adults ≥65 years, the age-standardized prevalence of falls was 32.4% (95% CI: 29.3-35.5%). Fallers were typically older, less mobile, had higher BMI and cholesterol levels, and were more likely to have musculoskeletal conditions, cancer, and polypharmacy. Men had a higher fall risk, but fewer fall-related fractures compared to women. Most falls occurred outdoors (62.1%), were due to extrinsic cause (58.5%), and were on the same level (78.5%). Factors associated with fall-related injuries included being female, elevated falls and falls outside the home. Nearly half (45.7%) of those injured sought medical attention, primarily from general practitioners (25.7%) and emergency departments (12.6%)., Conclusion: Falls are common, occurring in approximately one quarter of adults in this study, with a greater prevalence among those ≥65 years. Women experienced fewer multiple falls than men. Many participants sought medical attention, primarily from general practitioners. This research identifies fall characteristics and circumstances, informing targeted prevention strategies to reduce occurrences and alleviate burdens on healthcare systems and individuals., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yosef, Pasco, Tembo, Williams and Holloway-Kew.)

Objective: This study investigated the association between gait speed, handgrip strength, and their combination, and the risk for developing clinically relevant depressive symptoms in community-dwelling older adults., Methods: A secondary analysis was conducted using data from the ASPirin in Reducing Events in the Elderly study. Participants were community-dwelling older adults in Australia and the United States of America followed for a median (interquartile range) of 3.97 (2.26) years. Baseline handgrip strength and gait speed were used as exposure variables, and their combination categories were also explored. Depression was measured using the modified Center for Epidemiological Studies Depression 10-item scale (CES-D 10). Cox regression was used to estimate Adjusted Hazard Ratios (AHR) with 95 % Confidence Intervals (CI) after adjusting for a range of potential confounders., Result: A total of 17,231 participants (55.3 % women) were included in the analysis. Slow gait and weak grip at baseline were associated with the risk of depression (AHR: 1.20; CI: 1.11-1.29 and 1.14; 1.06-1.23, respectively). The combination of the two physical performance measures was associated with a 31 % increase in the risk of depression (1.31; 1.16-1.47) and a significant dose-response association was observed for quintiles of gait and grip with depression., Limitations: Although the CES-D 10 is a validated scale, it is a self-reported tool rather than a clinical diagnosis of depression., Conclusion: Low physical function may be a risk factor for depression in older adults. This highlights the inextricable link between the physical and mental health of older adults, which can inform potential clinical and public health prevention strategies for depression in later life., Competing Interests: Declaration of competing interest TC has received honoraria for lectures from Roche. The authors declare no conflicts of interest., (Crown Copyright © 2024. Published by Elsevier B.V. All rights reserved.)

The important trace elements, copper and selenium, have diverse effects on human health. As well as other important roles in living tissues, these trace elements are toxic at high levels but are key constituents of various enzymes and proteins essential for maintaining physiological health. However, links between dietary intakes of these elements, particularly copper, and bone mineral density (BMD) in humans remain uncertain. This study aimed to investigate whether dietary intakes of copper and selenium are associated with BMD in women. Dietary intakes of copper and selenium were assessed for 575 women in the Geelong Osteoporosis Study, using a detailed semi-quantitative food frequency questionnaire in conjunction with nutrition composition databases. Participants taking oral multivitamin preparations were excluded from analyses; 522 participants (ages 20-88 y) met the eligibility criteria. BMD at multiple skeletal sites was measured by dual energy X-ray absorptiometry (Lunar DPX-L). Separate multivariable regression models were developed to identify associations between copper and selenium intakes and BMD, after adjustments for age, anthropometry, other dietary factors, medication use, and lifestyle factors. Median (interquartile range) daily intake for copper was 1.5 mg (1.2-1.9) and for selenium, 72 μg (57-90). Low intakes (lowest tertile versus pooled upper tertiles) of copper and selenium were consistently associated with lower BMD at multiple skeletal sites. Fully adjusted models identified small but statistically significant differences in BMD, ranging from 1.8% to 4.0% for low copper intakes and 1.4% to 4.0% for low selenium intakes. Low dietary intakes of copper and selenium were both independently associated with lower BMD, at least in this sample of women. The results contribute to the evidence base for informing dietary recommendations for these trace elements with respect to their contributions to optimal bone health.

Introduction: Attention deficit hyperactivity disorder (ADHD) is a neuropsychiatric condition prevalent in both children and adults. With growing awareness of the importance of the preconception period in health, it is essential to understand whether preconception parental mental health and related factors are related to onset of offspring ADHD. This protocol presents the methodology for undertaking a systematic review to investigate associations between parental mental health and/or psychotropic use during the preconception years and offspring ADHD., Methods and Analysis: Peer-reviewed literature will be identified by searching relevant electronic databases including Medline complete, Embase, PsycINFO and CINAHL; reference lists of eligible articles will be hand searched and grey literature considered. Eligible study designs include population-based and/or clinically based cohort or case-control studies. The primary exposure and outcome of interest is parental history of mental health conditions in the preconception period and offspring ADHD, respectively (ie, according to semistructured interviews/confirmed diagnosis by a relevant health professional or screening instruments). Critical appraisal will be undertaken. A descriptive synthesis will be presented including characteristics of the included studies, critical appraisal scores and a summary of main findings (eg, presented in tables, text and figures). A meta-analysis will be conducted, if possible, and statistical techniques will be employed if heterogeneity is detected., Ethics and Dissemination: Ethical permissions are not required for this systematic review since the study will only use published data. Findings from this systematic review will be published in a peer-reviewed scientific journal/presented at national and international conferences relevant to the field., Prospero Registration Number: CRD42023460379., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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., Competing Interests: Conflicts of Interest There are no conflicts of interest to disclose., (Crown Copyright © 2024. Published by Elsevier B.V. All rights reserved.)

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, η 2  = 0.025, p < 0.001), psychomotor function (b 0.006 ± 0.002, η 2  = 0.028 p < 0.001) and attention (b 0.004 ± 0.001, η 2  = 0.021, p < 0.001), whereas psychotropic use was associated with lower overall cognitive function (b - 0.174 ± 0.075, η 2  = 0.010, p = 0.021), attention (b 0.017 ± 0.008, η 2  = 0.008, p = 0.038 and working memory (b 0.031 ± 0.012, η 2  = 0.010, p = 0.010). Anticonvulsant use was associated with lower overall cognitive function (b - 0.723 ± 0.172, η 2  = 0.032, p < 0.001), attention (b 0.065 ± 0.018, η 2  = 0.029, p < 0.001) and working memory (b 0.088 ± 0.026, η 2  = 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., Competing Interests: Declaration of competing interest J.A.P receives funding from the NHMRC, MRFF, Norman Beischer Foundation and Deakin University., (Copyright © 2024. Published by Elsevier B.V.)

Although patients believe that osteoporosis is a painful condition, health professionals assume it is painless unless a fracture occurs. The association between BMD and back pain has not been examined longitudinally in community-based adults in an unbiased population using gold-standard measures. This study aimed to examine the association between BMD and incident high-intensity back pain and/or high disability over 10 years in Australian men without high-intensity symptoms at baseline. Men with no high-intensity back pain and/or high disability attending the Geelong Osteoporosis Study at the 5-year visit (occurring between 2006-2010) (considered the baseline for the current study) were followed for 10 years (reassessed between 2016-2021). Back pain and disability were assessed using the Graded Chronic Pain Scale at both time points. At baseline, DXA was used to measure lumbar spine and total hip BMD and spinal artefacts. The relationships between BMD and incident high-intensity pain and/or high disability at follow-up were examined using binary logistic regression, adjusted for age, body mass index, depression, education, smoking, mobility, and spinal artefacts. A total of 679 participants had no to low-intensity pain and/or no to low disability at baseline. A total of 441 attended follow-up, providing back pain and disability data. Thirty-seven men developed high-intensity pain and/or high disability. No association of BMD at any site was seen with incident high-intensity pain and/or high disability. BMD was not associated with incident high-intensity pain or disability in community-based men. These data provide evidence to dispel the erroneous community-held belief that low BMD is related to back pain and disability., Competing Interests: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research.)

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., (© 2024 The Authors. Australian Journal of Rural Health published by John Wiley & Sons Australia, Ltd on behalf of National Rural Health Alliance Ltd.)

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., (© 2024. The Author(s).)

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 (BMD hip ) and lumbar spine (BMD spine ) bone mineral density (BMD) are routinely used to assess fracture risk. More data are needed to understand how ultra-distal forearm BMD (BMD UDforearm ) 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 BMD UDforearm 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 BMD UDforearm 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 BMD UDforearm , 33% forearm(BMD 33%forearm ), BMD hip , BMD spine , and FRAX without BMD were similar for any fracture (p > 0.05). For distal radius fracture, the AUROC for BMD UDforearm 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 BMD UDforearm , was higher than other sites and FRAX (p < 0.05)., Conclusion: Ultra-distal forearm BMD may aid risk assessments for any distal radius fractures., (© 2024. The Author(s).)

Schizophrenia is associated with increased risk of medical comorbidity, possibly including osteoporosis, which is a public health concern due to its significant social and health consequences. In this systematic review and meta-analysis, we aimed to determine whether schizophrenia is associated with bone fragility. The protocol for this review has been registered with PROSPERO (CRD42020171959). The research question and inclusion/exclusion criteria were developed and presented according to the PECO (Population, Exposure, Comparison, Outcome) framework. Schizophrenia was identified from medical records, DSM-IV/5 or the ICD. The outcomes for this review were bone fragility [i.e., bone mineral density (BMD), fracture, bone turnover markers, bone quality]. A search strategy was developed and implemented for the electronic databases. A narrative synthesis was undertaken for all included studies; the results from eligible studies reporting on BMD and fracture were pooled using a random effects model to complete a meta-analysis. The conduct of the review and reporting of results adhered to PRISMA guidelines. Our search yielded 3103 studies, of which 29 met the predetermined eligibility criteria. Thirty-seven reports from 29 studies constituted 17 studies investigating BMD, eight investigating fracture, three investigating bone quality and nine investigating bone turnover markers. The meta-analyses revealed that people with schizophrenia had lower BMD at the lumbar spine [standardised mean difference (SMD) -0.74, 95% CI -1.27, -0.20; Z = -2.71, p = 0.01] and at the femoral neck (SMD -0.78, 95% CI -1.03, -0.53; Z = -6.18, p ≤ 0.001). Also observed was a higher risk of fracture (OR 1.43, 95% CI 1.27, 1.61; Z = 5.88, p ≤ 0.001). Following adjustment for publication bias, the association between schizophrenia and femoral neck BMD (SMD -0.63, 95% CI -0.97, -0.29) and fracture (OR 1.32, 95% CI 1.28, 1.35) remained. Significantly increased risk of bone fragility was observed in people with schizophrenia. This association was independent of sex, participant number, methodological quality and year of publication., (© 2024. The Author(s).)

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., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.

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/cm 2 ) 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/cm 2 , p = 0.03), 4.2% greater at the total hip (0.979 [0.942-1.016] vs. 0.938 [0.910-0.966] g/cm 2 , 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/cm 2 , 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., (© 2024 The Authors. Acta Psychiatrica Scandinavica published by John Wiley & Sons Ltd.)

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 1.32 (95% CI 1.20-1.45) in women, P for interaction = 0.013). The HRs associated with previous falls decreased with age in women and with duration of follow-up in men and women for most fracture outcomes. There was no evidence of an interaction between falls and BMD for fracture risk. Subsequent risk for a major osteoporotic fracture increased with each additional previous fall in women and men., Conclusions: A previous self-reported fall confers an increased risk of fracture that is largely independent of BMD. Previous falls should be considered as an additional risk factor in future iterations of FRAX to improve fracture risk prediction., (© 2024. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

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., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Endocrinology.)

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., (© 2024. The Author(s).)

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., Competing Interests: AD-P owns shares of Active Life Scientific, Inc., the manufacturer of the RPI device. MAK and JAP are recipients of grants from the National Health and Medical Research Council (NHMRC) Australia, and KLH-K, MAK and JAP are recipients of grants from Amgen-GSK OA-ANZBMS and Amgen Australia. PR-M, KA and JH have no conflicts to declare., (© 2024 The Authors. Published by Elsevier Inc.)

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

A large international meta-analysis using primary data from 64 cohorts has quantified the increased risk of fracture associated with a previous history of fracture for future use in FRAX., Introduction: The aim of this study was to quantify the fracture risk associated with a prior fracture on an international basis and to explore the relationship of this risk with age, sex, time since baseline and bone mineral density (BMD)., Methods: We studied 665,971 men and 1,438,535 women from 64 cohorts in 32 countries followed for a total of 19.5 million person-years. The effect of a prior history of fracture on the risk of any clinical fracture, any osteoporotic fracture, major osteoporotic fracture, and hip fracture alone was examined using an extended Poisson model in each cohort. Covariates examined were age, sex, BMD, and duration of follow-up. The results of the different studies were merged by using the weighted β-coefficients., Results: A previous fracture history, compared with individuals without a prior fracture, was associated with a significantly increased risk of any clinical fracture (hazard ratio, HR = 1.88; 95% CI = 1.72-2.07). The risk ratio was similar for the outcome of osteoporotic fracture (HR = 1.87; 95% CI = 1.69-2.07), major osteoporotic fracture (HR = 1.83; 95% CI = 1.63-2.06), or for hip fracture (HR = 1.82; 95% CI = 1.62-2.06). There was no significant difference in risk ratio between men and women. Subsequent fracture risk was marginally downward adjusted when account was taken of BMD. Low BMD explained a minority of the risk for any clinical fracture (14%), osteoporotic fracture (17%), and for hip fracture (33%). The risk ratio for all fracture outcomes related to prior fracture decreased significantly with adjustment for age and time since baseline examination., Conclusion: A previous history of fracture confers an increased risk of fracture of substantial importance beyond that explained by BMD. The effect is similar in men and women. Its quantitation on an international basis permits the more accurate use of this risk factor in case finding strategies., (© 2023. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

Background: Recent operational definitions of sarcopenia have not been replicated and compared in Australia and New Zealand (ANZ) populations. We aimed to identify sarcopenia measures that discriminate ANZ adults with slow walking speed (<0.8 m/s) and determine the agreement between the Sarcopenia Definitions and Outcomes Consortium (SDOC) and revised European Working Group for Sarcopenia in Older People (EWGSOP2) operational definitions of sarcopenia., Methods: Eight studies comprising 8 100 ANZ community-dwelling adults (mean age ± standard deviation, 62.0 ± 14.4 years) with walking speed, grip strength (GR), and lean mass data were combined. Replicating the SDOC methodology, 15 candidate variables were included in sex-stratified classification and regression tree models and receiver operating characteristic curves on a pooled cohort with complete data to identify variables and cut points discriminating slow walking speed (<0.8 m/s). Agreement and prevalence estimates were compared using Cohen's Kappa (CK)., Results: Receiver operating characteristic curves identified GR as the strongest variable for discriminating slow from normal walking speed in women (GR <20.50 kg, area under curve [AUC] = 0.68) and men (GR <31.05 kg, AUC = 0.64). Near-perfect agreement was found between the derived ANZ cut points and SDOC cut points (CK 0.8-1.0). Sarcopenia prevalence ranged from 1.5% (EWGSOP2) to 37.2% (SDOC) in women and 1.0% (EWGSOP2) to 9.1% (SDOC) in men, with no agreement (CK <0.2) between EWGSOP2 and SDOC., Conclusions: Grip strength is the primary discriminating characteristic for slow walking speed in ANZ women and men, consistent with findings from the SDOC. Sarcopenia Definitions and Outcomes Consortium and EWGSOP2 definitions showed no agreement suggesting these proposed definitions measure different characteristics and identify people with sarcopenia differently., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Gerontological Society of America.)

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 (β = -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 (β = -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., Competing Interests: Kara Anderson, Pamela Rufus-Membere, Jacob Harland, Julie Pasco, Mark Kotowicz and Kara Holloway-Kew have no competing interests to declare. Adolfo Diez-Perez owns shares of Active Life Scientific, Inc., the manufacturer of the reference point indentation device., (© 2023 The Authors.)

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., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

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., (© 2023. The Author(s).)

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., (© 2023. The Author(s).)

Background: Certain age-related and medical factors have been associated with cognitive dysfunction; however, less is known regarding social determinants of health. The current study aimed to investigate associations between social determinants of health and cognitive function in a population-based sample of men without dementia., Methods: Data were drawn from the ongoing Geelong Osteoporosis Study (n = 536). Cognitive function was determined using the Cog-State Brief Battery. Area-based socioeconomic status (SES) was determined using the Index of Relative Socioeconomic Advantage and Disadvantage, marital status by self-report, and social support by the Multidimensional Scale of Perceived Social Support, which considers family, friends, and significant others., Results: Belonging to a higher SES group, being in a relationship (married/de-facto) and perceived social support from a significant other and friends were each associated with better overall cognitive function. In regard to the specific cognitive domains, higher SES was associated with better psychomotor function and visual learning, being in a relationship was associated with better working memory, and perceived social support from a significant other was associated with better attention and working memory, with perceived social support from friends associated with better psychomotor function. There were no associations detected between social support from family and any of the cognitive domains., Conclusion: Higher SES, being in a relationship, and greater perceived social support from a significant other and friends were associated with better cognitive function. Further studies identifying underlying mechanisms linking social factors with cognition are needed to establish prevention strategies and enhance cognitive health., (© 2023 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Objective: To examine mental health emergency presentations across the Barwon South West, Victoria, Australia - an area comprising a range of urban and rural localities., Methods: This is a retrospective synthesis of mental health emergency presentations across the Barwon South West (1 February 2017-31 December 2019). De-identified data were obtained from individuals who presented to EDs and urgent care centres (UCCs) within the study region, who had a principal diagnosis of a Mental and Behavioural Disorder (codes F00-F99). Data were sourced from the Victorian Emergency Minimum Dataset and Rural Acute Hospital Database Register (RAHDaR). Age-standardised incident rates for mental health emergency presentations were calculated for the whole sample and for local government areas. Data on usual accommodation, arrival transport mode, referral source, patient disposition and length of ED/UCC stay were also obtained., Results: We identified 11 613 mental health emergency presentations, with neurotic, stress-related and somatoform disorders (n = 3139, 27.0%) and mental and behavioural disorders due to psychoactive substance use (n = 3487, 30.0%) being the most frequent types of presentations recorded. The highest age-standardised incidence rates (mental health diagnosis per 1000 population/year) were in Glenelg (13.95), whereas Queenscliffe had the lowest incident rates (3.76). Most presentations (n = 3851, 33.2%) tended to occur for individuals aged between 15 and 29 years., Conclusions: Neurotic, stress-related and somatoform disorders and mental and behavioural disorders due to psychoactive substance use were the most frequent types of presentations recorded across the sample. RAHDaR represented a small but meaningful contribution to the data., (© 2023 The Authors. Emergency Medicine Australasia published by John Wiley & Sons Australia, Ltd on behalf of Australasian College for Emergency Medicine.)

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/m 2 ), body fat percentage (≥35%) and body mass index (≥30 kg/m 2 ); 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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Pasco, Berk, Penninx, Hyde, Holloway-Kew, West, Kotowicz, Anderson, O’Neil, Rufus-Membere and Williams.)

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., (© 2023. BioMed Central Ltd., part of Springer Nature.)