Opposite associations between alanine aminotransferase and γ-glutamyl transferase levels and all-cause mortality in type 2 diabetes: Analysis of the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study.

AIMS: Reported associations between liver enzymes and mortality may not hold true in type 2 diabetes, owing to a high prevalence of non-alcoholic fatty liver disease, which has been linked to cardiovascular disease and mortality in its own right. Our study aimed to determine whether alanine aminotransferase (ALT) or γ-glutamyl transferase (GGT) levels predict mortality in type 2 diabetes, and to examine possible mechanisms. METHODS: Data from the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study were analyzed to examine the relationship between liver enzymes and all-cause and cause-specific mortality over 5years. RESULTS: Over 5years, 679 (6.9%) individuals died. After adjustment, for every standard deviation increase in ALT (13.2U/L), the HR for death on study was 0.85 (95% CI 0.78-0.93), p<0.001. Conversely, GGT >70U/L, compared with GGT ≤70U/L, had HR 1.82 (1.48-2.24), p<0.001. For cause-specific mortality, lower ALT was associated with a higher risk of cardiovascular death only, whereas GGT >70U/L was associated with higher risks of death due to cardiovascular disease, cancer and non-cancer/non-cardiovascular causes. The relationship for ALT persisted after adjustment for indirect measures of frailty but was attenuated by elevated hsCRP. CONCLUSIONS: As in the general population, ALT has a negative, and GGT a positive, correlation with mortality in type 2 diabetes when ALT is less than two times the upper limit of normal. The relationship for ALT appears specific for death due to cardiovascular disease. Links of low ALT with frailty, as a potential mechanism for relationships seen, were neither supported nor conclusively refuted by our analysis and other factors are also likely to be important in those with type 2 diabetes.

Multistage genome-wide association meta-analyses identified two new loci for bone mineral density.

Aiming to identify novel genetic variants and to confirm previously identified genetic variants associated with bone mineral density (BMD), we conducted a three-stage genome-wide association (GWA) meta-analysis in 27 061 study subjects. Stage 1 meta-analyzed seven GWA samples and 11 140 subjects for BMDs at the lumbar spine, hip and femoral neck, followed by a Stage 2 in silico replication of 33 SNPs in 9258 subjects, and by a Stage 3 de novo validation of three SNPs in 6663 subjects. Combining evidence from all the stages, we have identified two novel loci that have not been reported previously at the genome-wide significance (GWS; 5.0 × 10(-8)) level: 14q24.2 (rs227425, P-value 3.98 × 10(-13), SMOC1) in the combined sample of males and females and 21q22.13 (rs170183, P-value 4.15 × 10(-9), CLDN14) in the female-specific sample. The two newly identified SNPs were also significant in the GEnetic Factors for OSteoporosis consortium (GEFOS, n = 32 960) summary results. We have also independently confirmed 13 previously reported loci at the GWS level: 1p36.12 (ZBTB40), 1p31.3 (GPR177), 4p16.3 (FGFRL1), 4q22.1 (MEPE), 5q14.3 (MEF2C), 6q25.1 (C6orf97, ESR1), 7q21.3 (FLJ42280, SHFM1), 7q31.31 (FAM3C, WNT16), 8q24.12 (TNFRSF11B), 11p15.3 (SOX6), 11q13.4 (LRP5), 13q14.11 (AKAP11) and 16q24 (FOXL1). Gene expression analysis in osteogenic cells implied potential functional association of the two candidate genes (SMOC1 and CLDN14) in bone metabolism. Our findings independently confirm previously identified biological pathways underlying bone metabolism and contribute to the discovery of novel pathways, thus providing valuable insights into the intervention and treatment of osteoporosis.

Cord blood-derived macrophage-lineage cells rapidly stimulate osteoblastic maturation in mesenchymal stem cells in a glycoprotein-130 dependent manner.

In bone, depletion of osteoclasts reduces bone formation in vivo, as does osteal macrophage depletion. How osteoclasts and macrophages promote the action of bone forming osteoblasts is, however, unclear. Since recruitment and differentiation of multi-potential stromal cells/mesenchymal stem cells (MSC) generates new active osteoblasts, we investigated whether human osteoclasts and macrophages (generated from cord blood-derived hematopoietic progenitors) induce osteoblastic maturation in adipose tissue-derived MSC. When treated with an osteogenic stimulus (ascorbate, dexamethasone and ß-glycerophosphate) these MSC form matrix-mineralising, alkaline phosphatase-expressing osteoblastic cells. Cord blood-derived progenitors were treated with macrophage colony stimulating factor (M-CSF) to form immature proliferating macrophages, or with M-CSF plus receptor activator of NFκB ligand (RANKL) to form osteoclasts; culture medium was conditioned for 3 days by these cells to study their production of osteoblastic factors. Both osteoclast- and macrophage-conditioned medium (CM) greatly enhanced MSC osteoblastic differentiation in both the presence and absence of osteogenic medium, evident by increased alkaline phosphatase levels within 4 days and increased mineralisation within 14 days. These CM effects were completely ablated by antibodies blocking gp130 or oncostatin M (OSM), and OSM was detectable in both CM. Recombinant OSM very potently stimulated osteoblastic maturation of these MSC and enhanced bone morphogenetic protein-2 (BMP-2) actions on MSC. To determine the influence of macrophage activation on this OSM-dependent activity, CM was collected from macrophage populations treated with M-CSF plus IL-4 (to induce alternative activation) or with GM-CSF, IFNγ and LPS to cause classical activation. CM from IL-4 treated macrophages stimulated osteoblastic maturation in MSC, while CM from classically-activated macrophages did not. Thus, macrophage-lineage cells, including osteoclasts but not classically activated macrophages, can strongly drive MSC-osteoblastic commitment in OSM-dependent manner. This supports the notion that eliciting gp130-dependent signals in human MSC would be a useful approach to increase bone formation.

A novel serogenetic approach determines the community prevalence of celiac disease and informs improved diagnostic pathways.

BACKGROUND: Changing perspectives on the natural history of celiac disease (CD), new serology and genetic tests, and amended histological criteria for diagnosis cast doubt on past prevalence estimates for CD. We set out to establish a more accurate prevalence estimate for CD using a novel serogenetic approach. METHODS: The human leukocyte antigen (HLA)-DQ genotype was determined in 356 patients with 'biopsy-confirmed' CD, and in two age-stratified, randomly selected community cohorts of 1,390 women and 1,158 men. Sera were screened for CD-specific serology. RESULTS: Only five 'biopsy-confirmed' patients with CD did not possess the susceptibility alleles HLA-DQ2.5, DQ8, or DQ2.2, and four of these were misdiagnoses. HLA-DQ2.5, DQ8, or DQ2.2 was present in 56% of all women and men in the community cohorts. Transglutaminase (TG)-2 IgA and composite TG2/deamidated gliadin peptide (DGP) IgA/IgG were abnormal in 4.6% and 5.6%, respectively, of the community women and 6.9% and 6.9%, respectively, of the community men, but in the screen-positive group, only 71% and 75%, respectively, of women and 65% and 63%, respectively, of men possessed HLA-DQ2.5, DQ8, or DQ2.2. Medical review was possible for 41% of seropositive women and 50% of seropositive men, and led to biopsy-confirmed CD in 10 women (0.7%) and 6 men (0.5%), but based on relative risk for HLA-DQ2.5, DQ8, or DQ2.2 in all TG2 IgA or TG2/DGP IgA/IgG screen-positive subjects, CD affected 1.3% or 1.9%, respectively, of females and 1.3% or 1.2%, respectively, of men. Serogenetic data from these community cohorts indicated that testing screen positives for HLA-DQ, or carrying out HLA-DQ and further serology, could have reduced unnecessary gastroscopies due to false-positive serology by at least 40% and by over 70%, respectively. CONCLUSIONS: Screening with TG2 IgA serology and requiring biopsy confirmation caused the community prevalence of CD to be substantially underestimated. Testing for HLA-DQ genes and confirmatory serology could reduce the numbers of unnecessary gastroscopies.

Impact of denosumab on the peripheral skeleton of postmenopausal women with osteoporosis: bone density, mass, and strength of the radius, and wrist fracture.

OBJECTIVE: The aim of this study was to report the effects of denosumab on radius cortical and trabecular bone density, mass, and strength, and wrist fracture incidence in the FREEDOM (Fracture REduction Evaluation of Denosumab in Osteoporosis every 6 Months) study. METHODS: In the FREEDOM study, postmenopausal women with osteoporosis (N = 7,808) received placebo or 60 mg of denosumab every 6 months for 36 months. Radius bone mineral density (BMD), bone mineral content, and strength (polar moment of inertia) were evaluated in two prespecified substudies using dual-energy x-ray absorptiometry (placebo, n = 209; denosumab, n = 232) or quantitative CT (placebo, n = 48; denosumab, n = 62). Prespecified analysis assessed wrist fracture incidence in all FREEDOM participants (placebo, N = 3,906; denosumab, N = 3,902), and post hoc subgroup analyses evaluated those with higher fracture risk (baseline femoral neck T-score ≤-2.5; placebo, N = 1,406; denosumab, N = 1,384). RESULTS: Denosumab significantly increased areal BMD (assessed by dual-energy x-ray absorptiometry) and volumetric BMD, bone mineral content, and polar moment of inertia (assessed by quantitative CT), compared with placebo, in radius cortical and trabecular bone at all time points evaluated (all P < 0.05). Wrist fracture incidence was 2.9% for placebo and 2.5% for denosumab (relative risk reduction, 16%; P = 0.21) on month 36. Participants with a femoral neck T-score of -2.5 or lower were at increased risk for wrist fracture, and denosumab significantly reduced wrist fracture incidence compared with placebo (placebo, 4.0%; denosumab, 2.4%; relative risk reduction, 40%; absolute risk reduction, 1.6%; P = 0.03). CONCLUSIONS: Denosumab significantly improves radius bone density, mass, and strength compared with placebo. In higher-risk women, denosumab significantly reduces wrist fracture risk.

Cross-sectional analysis of association between socioeconomic status and utilization of primary total hip joint replacements 2006-7: Australian Orthopaedic Association National Joint Replacement Registry.

BACKGROUND: The utilization of total hip replacement (THR) surgery is rapidly increasing, however few data examine whether these procedures are associated with socioeconomic status (SES) within Australia. This study examined primary THR across SES for both genders for the Barwon Statistical Division (BSD) of Victoria, Australia. METHODS: Using the Australian Orthopaedic Association National Joint Replacement Registry data for 2006-7, primary THR with a diagnosis of osteoarthritis (OA) among residents of the BSD was ascertained. The Index of Relative Socioeconomic Disadvantage was used to measure SES; determined by matching residential addresses with Australian Bureau of Statistics census data. The data were categorised into quintiles; quintile 1 indicating the most disadvantaged. Age- and sex-specific rates of primary THR per 1,000 person years were reported for 10-year age bands using the total population at risk. RESULTS: Females accounted for 46.9% of the 642 primary THR performed during 2006-7. THR utilization per 1,000 person years was 1.9 for males and 1.5 for females. The highest utilization of primary THR was observed in those aged 70-79 years (males 6.1, and females 5.4 per 1,000 person years). Overall, the U-shaped pattern of THR across SES gave the appearance of bimodality for both males and females, whereby rates were greater for both the most disadvantaged and least disadvantaged groups. CONCLUSIONS: Further work on a larger scale is required to determine whether relationships between SES and THR utilization for the diagnosis of OA is attributable to lifestyle factors related to SES, or alternatively reflects geographic and health system biases. Identifying contributing factors associated with SES may enhance resource planning and enable more effective and focussed preventive strategies for hip OA.

Dietary selenium and major depression: a nested case-control study.

OBJECTIVES AND METHODS: Alterations in redox biology are established in depression; however, there are no prospective epidemiological data on redox-active selenium in depression. We aimed to determine if low levels of dietary selenium are associated with an increased risk for de novo major depressive disorder (MDD). In this nested case-control study, women aged 20 years or more were identified from a randomly selected cohort being followed prospectively for the Geelong Osteoporosis Study. Cases were individuals with incident MDD, identified using the Structured Clinical Interview for DSM-IV-TR (SCID-I/NP); controls had no such history. Dietary selenium intake was measured using a food frequency questionnaire at baseline, together with anthropometric and lifestyle measures. RESULTS: Eighteen women who developed de novo MDD were classified as cases; there were 298 controls. Low dietary selenium intakes increased the likelihood of developing MDD; OR 2.74 (95%CI 0.95-7.89). After adjusting for age and SES, compared with a high selenium intake, a low intake (<8.9 µg/MJ/day) was associated with an approximate trebling of the likelihood for developing de novo MDD; OR 2.95 (95%CI 1.00-8.72). Smoking, alcohol consumption and physical activity did not confound the association. CONCLUSION: These data suggest that lower dietary selenium intakes are associated with an increased risk of subsequent de novo MDD. We propose that selenium's function as an antioxidant, and as a constituent of selenoproteins that are important in redox homeostasis, warrants further investigation as a risk factor for depression, and suggest a potentially novel modifiable factor in the primary prevention and management of depression.

M-CSF potently augments RANKL-induced resorption activation in mature human osteoclasts.

Macrophage-CSF (M-CSF) is critical for osteoclast (OC) differentiation and is reported to enhance mature OC survival and motility. However, its role in the regulation of bone resorption, the main function of OCs, has not been well characterised. To address this we analysed short-term cultures of fully differentiated OCs derived from human colony forming unit-granulocyte macrophages (CFU-GM). When cultured on dentine, OC survival was enhanced by M-CSF but more effectively by receptor activator of NFκB ligand (RANKL). Resorption was entirely dependent on the presence of RANKL. Co-treatment with M-CSF augmented RANKL-induced resorption in a concentration-dependent manner with a (200-300%) stimulation at 25 ng/mL, an effect observed within 4-6 h. M-CSF co-treatment also increased number of resorption pits and F-actin sealing zones, but not the number of OCs or pit size, indicating stimulation of the proportion of OCs activated. M-CSF facilitated RANKL-induced activation of c-fos and extracellular signal-regulated kinase (ERK) 1/2 phosphorylation, but not NFκB nor nuclear factor of activated T-cells, cytoplasmic-1 (NFATc1). The mitogen-activated protein kinase kinase (MEK) 1 inhibitor PD98059 partially blocked augmentation of resorption by M-CSF. Our results reveal a previously unidentified role of M-CSF as a potent stimulator of mature OC resorbing activity, possibly mediated via ERK upstream of c-fos.

Genome-wide association study using extreme truncate selection identifies novel genes affecting bone mineral density and fracture risk.

Osteoporotic fracture is a major cause of morbidity and mortality worldwide. Low bone mineral density (BMD) is a major predisposing factor to fracture and is known to be highly heritable. Site-, gender-, and age-specific genetic effects on BMD are thought to be significant, but have largely not been considered in the design of genome-wide association studies (GWAS) of BMD to date. We report here a GWAS using a novel study design focusing on women of a specific age (postmenopausal women, age 55-85 years), with either extreme high or low hip BMD (age- and gender-adjusted BMD z-scores of +1.5 to +4.0, n = 1055, or -4.0 to -1.5, n = 900), with replication in cohorts of women drawn from the general population (n = 20,898). The study replicates 21 of 26 known BMD-associated genes. Additionally, we report suggestive association of a further six new genetic associations in or around the genes CLCN7, GALNT3, IBSP, LTBP3, RSPO3, and SOX4, with replication in two independent datasets. A novel mouse model with a loss-of-function mutation in GALNT3 is also reported, which has high bone mass, supporting the involvement of this gene in BMD determination. In addition to identifying further genes associated with BMD, this study confirms the efficiency of extreme-truncate selection designs for quantitative trait association studies.

Interleukin-33, a target of parathyroid hormone and oncostatin m, increases osteoblastic matrix mineral deposition and inhibits osteoclast formation in vitro.

IL-33 is an important inflammatory mediator in allergy, asthma, and joint inflammation, acting via its receptor, ST2L, to elicit Th2 cell cytokine secretion. IL-33 is related to IL-1 and IL-18, which both influence bone metabolism, IL-18 in particular inhibiting osteoclast formation and contributing to PTH bone anabolic actions. We found IL-33 immunostaining in osteoblasts in mouse bone and IL-33 mRNA expression in cultured calvarial osteoblasts, which was elevated by treatment with the bone anabolic factors oncostatin M and PTH. IL-33 treatment strongly inhibited osteoclast formation in bone marrow and spleen cell cultures but had no effect on osteoclast formation in receptor activator of nuclear factor-κB ligand/macrophage colony-stimulating factor-treated bone marrow macrophage (BMM) or RAW264.7 cultures, suggesting a lack of direct action on immature osteoclast progenitors. However, osteoclast formation from BMM was inhibited by IL-33 in the presence of osteoblasts, T cells, or mature macrophages, suggesting these cell types may mediate some actions of IL-33. In bone marrow cultures, IL-33 induced mRNA expression of granulocyte macrophage colony-stimulating factor, IL-4, IL-13, and IL-10; osteoclast inhibitory actions of IL-33 were rescued only by combined antibody ablation of these factors. In contrast to osteoclasts, IL-33 promoted matrix mineral deposition by long-term ascorbate treated primary osteoblasts and reduced sclerostin mRNA levels in such cultures after 6 and 24 h of treatment; sclerostin mRNA was also suppressed in IL-33-treated calvarial organ cultures. In summary, IL-33 stimulates osteoblastic function in vitro but inhibits osteoclast formation through at least three separate mechanisms. Autocrine and paracrine actions of osteoblast IL-33 may thus influence bone metabolism.

Paracetamol (acetaminophen) use, fracture and bone mineral density.

Paracetamol is the most widely prescribed simple analgesic and antipyretic. It exerts its effects via cyclooxygenase and endocannabinoid pathways, which may affect signalling in bone cells and hence influence bone metabolism. Given the high rates of paracetamol use in the community and the evidence linking its mechanism of action to bone metabolism, we aimed to investigate the association between paracetamol use, fracture, and bone mineral density (BMD) in women participating in the Geelong Osteoporosis Study (GOS). Cases (n = 569) were women aged ≥ 50 years identified from radiological reports as having sustained a fracture between 1994 and 1996. Controls (n = 775) were women without fracture recruited from the same region during this period. BMD was measured at the spine, hip, total body and forearm using dual energy absorptiometry. Medication use, medical history and lifestyle factors were self-reported. There were 69 (12.1%) paracetamol users among the cases and 63 (8.1%) among the controls. Paracetamol use increased the odds for fracture (OR = 1.56, 95%CI 1.09-2.24, p = 0.02). Adjustment for BMD at the spine, total hip and forearm did not confound the association. However, incorporating total body BMD into the model attenuated the association (adjusted OR = 1.46, 95%CI 1.00-2.14, p = 0.051). Further adjustment for age, weight, physical activity, smoking, alcohol, calcium intake, medication use, medical conditions, falls and previous fracture did not explain the association. These data suggest that paracetamol use is a risk factor for fracture, although the mechanism of action remains unclear.

Habitual physical activity and the risk for depressive and anxiety disorders among older men and women.

BACKGROUND: Regular physical activity is generally associated with psychological well-being, although there are relatively few prospective studies in older adults. We investigated habitual physical activity as a risk factor for de novo depressive and anxiety disorders in older men and women from the general population. METHODS: In this nested case-control study, subjects aged 60 years or more were identified from randomly selected cohorts being followed prospectively in the Geelong Osteoporosis Study. Cases were individuals with incident depressive or anxiety disorders, diagnosed using the Structured Clinical Interview for DSM-IV-TR (SCID-I/NP); controls had no history of these disorders. Habitual physical activity, measured using a validated questionnaire, and other exposures were documented at baseline, approximately four years prior to psychiatric interviews. Those with depressive or anxiety disorders that pre-dated baseline were excluded. RESULTS: Of 547 eligible subjects, 14 developed de novo depressive or anxiety disorders and were classified as cases; 533 controls remained free of disease. Physical activity was protective against the likelihood of depressive and anxiety disorders; OR = 0.55 (95% CI 0.32-0.94), p = 0.03; each standard deviation increase in the transformed physical activity score was associated with an approximate halving in the likelihood of developing depressive or anxiety disorders. Leisure-time physical activity contributed substantially to the overall physical activity score. Age, gender, smoking, alcohol consumption, weight and socioeconomic status did not substantially confound the association. CONCLUSION: This study provides evidence consistent with the notion that higher levels of habitual physical activity are protective against the subsequent risk of development of de novo depressive and anxiety disorders.

Association of high-sensitivity C-reactive protein with de novo major depression.

BACKGROUND: Although there is cross-sectional evidence that changes in the immune system contribute to the pathophysiology of depression, longitudinal data capable of elucidating cause and effect relationships are lacking. AIMS: We aimed to determine whether subclinical systemic inflammation, as measured by serum high-sensitivity C-reactive protein (hsCRP) concentration, is associated with an increased risk of de novo major depressive disorder. METHOD: Major depressive disorder was diagnosed using a clinical interview (SCID-I/NP). This is a retrospective cohort study; from a population-based sample of 1494 randomly selected women recruited at baseline during the period 1994-7, 822 were followed for a decade and provided measures of both exposure and outcome. Of these women, 644 (aged 20-84 years) had no prior history of depression at baseline and were eligible for analysis. RESULTS: During 5827 person-years of follow-up, 48 cases of de novo major depressive disorder were identified. The hazard ratio (HR) for depression increased by 44% for each standard deviation increase in log-transformed hsCRP (ln-hsCRP) (HR = 1.44, 95% CI 1.04-1.99), after adjusting for weight, smoking and use of non-steroidal anti-inflammatory drugs. Further adjustment for other lifestyle factors, medications and comorbidity failed to explain the observed increased risk for depression. CONCLUSIONS: Serum hsCRP is an independent risk marker for de novo major depressive disorder in women. This supports an aetiological role for inflammatory activity in the pathophysiology of depression.

Patterns of alcohol use and associated physical and lifestyle characteristics according to new Australian guidelines.

OBJECTIVE: To describe the pattern of alcohol consumption and associated physical and lifestyle characteristics in a population-based sample of Australian men. METHOD: A community-based age-stratified random sample of 1420 men (median age 56 years, range 20-93) participating in the Geelong Osteoporosis Study, an epidemiological study set in south-eastern Australia. Daily alcohol intake was ascertained from a detailed food frequency questionnaire and categorized according to the Australian National Health and Medical Research Council 2009 guidelines (non-drinkers, greater than zero but ≤ 2 drinks per day, > 2 drinks per day), with a standard drink equivalent to 10 g of ethanol. Anthropometry was measured and lifestyle factors self-reported. Body composition was determined using dual energy absorptiometry. Socio-economic status was categorized according to the Australian Bureau of Statistics data. Results were age standardized to the Australian male population figures. RESULTS: The median daily ethanol consumption was 12 g (IQR 2-29) per day with a range of 0-117 g/day. The age-standardized proportion of non-drinkers was 8.7%, 51.5% consumed up to two drinks per day (≤ 20 g ethanol/day), and 39.9% exceeded 2 standard drinks per day (> 20 g ethanol/day). Alcohol consumption was positively associated with cigarette smoking, weight, higher SES and inversely with age and physical activity. CONCLUSIONS: Approximately, 40% of Australian men consume alcohol at levels in excess of current recommendations, which in combination with other risk factors may adversely impact upon health.

Socioeconomic status and risk factors for obesity and metabolic disorders in a population-based sample of adult females.

OBJECTIVES: The association between lower socioeconomic status (SES), obesity, lifestyle choices and adverse health consequences are well documented, however to date the relationship between these variables and area-based SES (equivalised for advantage and disadvantage) has not been examined simultaneously in one population or with more than tertiary divisions of SES. We set out to examine the risk factors for obesity and metabolic disorders in the same population across quintiles of area-based SES. METHODS: We performed a descriptive cross-sectional study using existing data from a population-based random selection of women aged 20-92 years (n=1110) recruited from the Barwon Statistical Division, South Eastern Australia. RESULTS: All measures of adiposity were inversely associated with SES, and remained significant after adjusting for age. Lifestyle choices associated with adiposity and poorer health, including smoking, larger serving sizes of foods, and reduced physical activity, were significantly associated with individuals from lower SES groups. CONCLUSIONS: Greater measures of adiposity and less healthy lifestyle choices were observed in individuals from lower SES. Significant differences in body composition were identified between quintiles 1 and 5, whereas subjects in the mid quintiles had relatively similar measures. The inverse relationship between SES, obesity and less healthy lifestyle underscores the possibility that these associations may be causal and should be investigated further.

Health outcomes associated with hormone therapy in Australian women.

The risks and benefits of hormone therapy (HT) in the treatment of postmenopausal women remain controversial. In this population-based, observational study, we documented health outcomes among postmenopausal Australian women using HT. Women aged 60-80 years were recruited into the Geelong Osteoporosis Study 1994-7 and followed over a median period of 6.6 years. Mortality, and the development of vascular events, breast and colorectal cancers were documented for 67 HT-users and 521 non-users. Median duration of HT-use was 5.0 years (IQR 3.0-10.0). There was no excess in all-cause mortality associated with HT-use. Based on 92 deaths (six HT-users, 86 non-users), the adjusted odds ratio (OR) for all-cause mortality was 0.79 (95%CI 0.32-1.97). With 99 reports of vascular events (13 HT-users, 86 non-users), the adjusted OR for vascular events was 1.30 (95%CI 0.66-2.57). There were insufficient numbers of breast or colorectal cancer cases (21 breast cancer cases, all non-HT users; and 7 colorectal cancer cases, one HT-user and six non-users) to adequately calculate the risk associated with exposure to HT. Although the sample size was small, these results do not support an association between HT and mortality, despite a possible link between HT and increased risk of developing vascular disease.

Behavioural and physical characteristics associated with vitamin D status in women.

For most people in Australia, the primary source of vitamin D is casual exposure to sunlight. Hypovitaminosis D has been reported for high-risk populations, but little has been documented for women of all ages living in the community. Using cross-sectional data, we aimed to describe physical and behavioural characteristics associated with serum 25-hydroxyvitamin D (25OHD) for such women and to determine the association of serum 25OHD with hypertension and bone health. Serum 25OHD, parathyroid hormone (PTH), blood pressure, bone mineral density (BMD) and anthropometry were measured in a random sample of 861 women aged 20-92 years enrolled in the Geelong Osteoporosis Study, set in a temperate region at latitude 38-39 degrees S. Lifestyle factors (including diet, smoking, medication use, socio-economic status, residence, education, occupation, and physical activity) were documented by questionnaire. In season-adjusted models for women aged 20-54 years, physical activity and living with a partner were independently and positively associated with serum 25OHD; associations with weight and waist-hip ratio were negative. Among older women, physical activity, vitamin D intake and urban dwelling were positively associated with serum 25OHD; age, weight and smoking were negative. Compared with the lowest tertile, those in the highest serum 25OHD tertile were less likely to have elevated serum PTH (adjusted OR=0.25, 95% CI 0.16-0.41) and high blood pressure (adjusted OR=0.40, 95% CI 0.22-0.72), and more likely to have normal hip and spine BMD (adjusted OR=1.65, 95% CI 1.08-2.52). In multivariable models adjusting for season, age, weight (and height), BMD was associated with serum 25OHD at the spine, hip and whole body; no associations were detected at the forearm and no other characteristics were identified as confounders. Factors associated with high vitamin D status generally reflected healthy body habitus and active lifestyles. In contrast, excessive weight and smoking were associated with poorer vitamin D status. Women with high vitamin D were less likely to have elevated PTH, hypertension or bone deficits than women with poor levels.

Lifetime psychiatric disorders and body composition: a population-based study.

BACKGROUND: This study aimed to investigate the relationship between depressive and anxiety disorders and indices of adiposity, including body fat mass and percent body fat, as measured by dual energy X-ray absorptiometry. METHODS: In this observational study of 979 randomly-selected women aged 20-93 years, psychiatric history was ascertained using a structured clinical interview (SCID-I/NP). Total body fat was assessed using dual-energy X-ray absorptiometry and weight, height and waist circumference were measured. Medication use and lifestyle factors were self-reported. RESULTS: Those with a lifetime history of depression had increased fat mass (+7.4%) and percent body fat (+4.3%), as well as greater mean weight (+3.3%), waist circumference (+2.9%) and BMI (+3.5%) after adjustment for age, anxiety, alcohol consumption, physical activity and past smoking. Furthermore, those meeting criteria for a lifetime history of depression had a 1.7-fold increased odds of being overweight or obese (BMI>or=25), a 2.0-fold increased odds of being obese (BMI>or=30) and a 1.8-fold increased odds of having a waist circumference >or=80 cm. These patterns persisted after further adjustment for psychotropic medication use, smoking status and energy intake. No differences in any measures of adiposity were observed among those with anxiety disorders compared to controls. LIMITATIONS: There is potential for unrecognised confounding, interpretations are limited to women and a temporal relationship could not be inferred. CONCLUSIONS: Depression was associated with greater adiposity. The difference in body fat mass was numerically greater than differences in indirect measures of adiposity, suggesting that the latter may underestimate the extent of adiposity in this population.

BMD in population-based adult women is associated with socioeconomic status.

With few exceptions, an inverse relationship exists between social disadvantage and disease. However, there are conflicting data for the relationship between socioeconomic status (SES) and BMD. The aim of this study was to assess the association between SES and lifestyle exposures in relation to BMD. In a cross-sectional study conducted using 1494 randomly selected population-based adult women, we assessed the association between SES and lifestyle exposures in relation to BMD. BMD was measured at multiple anatomical sites by DXA. SES was determined by cross-referencing residential addresses with Australian Bureau of Statistics 1996 census data for the study region and categorized in quintiles. Lifestyle variables were collected by self-report. Regression models used to assess the relationship between SES and BMD were adjusted for age, height, weight, dietary calcium, smoking, alcohol consumption, physical activity, hormone therapy, and calcium/vitamin D supplements. Unadjusted BMD differed across SES quintiles (p < 0.05). At each skeletal site and SES index, a consistent peak in adjusted BMD was observed in the mid-quintiles. Differences in adjusted BMD were observed between SES quintiles 1 and 4 (3-7%) and between quintiles 5 and 4 (2-7%). At the spine, the maximum difference was observed (7.5%). In a subset of women, serum 25(OH)D explained a proportion of the association between SES and BMD (difference remained up to 4.2%). Observed differences in BMD across SES quintiles, consistent across both SES indices, suggest that low BMD may be evident for both the most disadvantaged and most advantaged.

Tobacco smoking as a risk factor for major depressive disorder: population-based study.

BACKGROUND: Smoking is disproportionately prevalent among people with psychiatric illness. AIMS: To investigate smoking as a risk factor for major depressive disorder. METHOD: A population-based sample of women was studied using case-control and retrospective cohort study designs. Exposure to smoking was self-reported, and major depressive disorder diagnosed using the Structured Clinical Interview for DSM-IV-TR (SCID-I/NP). RESULTS: Among 165 people with major depressive disorder and 806 controls, smoking was associated with increased odds for major depressive disorder (age-adjusted odds ratio (OR)=1.46, 95% CI 1.03-2.07). Compared with non-smokers, odds for major depressive disorder more than doubled for heavy smokers (>20 cigarettes/day). Among 671 women with no history of major depressive disorder at baseline, 13 of 87 smokers and 38 of 584 non-smokers developed de novo major depressive disorder during a decade of follow-up. Smoking increased major depressive disorder risk by 93% (hazard ratio (HR)=1.93, 95% CI 1.02-3.69); this was not explained by physical activity or alcohol consumption. CONCLUSIONS: Evidence from cross-sectional and longitudinal data suggests that smoking increases the risk of major depressive disorder in women.