Retrospective analysis of cancer survival across South-Western Victoria in Australia.

OBJECTIVE: This paper aims to describe cancer survival and examine association between survival and socio-demographic characteristics across Barwon South-Western region (BSWR) in Victoria, Australia. DESIGN: This study is based on the retrospective cohort database of patients accessing oncology services across BSWR. SETTING: Six rural and three urban hospital settings across the BSWR. PARTICIPANTS: The participants were patients who were diagnosed with cancer in 2009. MAIN OUTCOME MEASURES: Overall survival (OS) of participants was the main outcome measure. RESULTS: Total of 1778 eligible patients had four-year OS for all cancers combined of 59.7% (95% CI, 57.4-62.0). Improved OS was observed for patients in the upper socio-economic tertile (64.2%; 95% CI, 60.9-67.5) compared to the middle (59.3%; 95% CI, 55.5-63.1) and lowest tertiles (49.6%; 95% CI, 44.2-54.9) (P < 0.01). On multivariate analyses, higher socio-economic status remained a significant predictor of OS adjusting for gender, remoteness and age (HR [hazard ratio] 0.81; 95% CI 0.74-0.89; P < 0.01). Remoteness was significantly associated with improved OS after adjusting for age, gender and socio-economic status (HR 0.86; 95% CI, 0.77-0.97; P = 0.01). Older age ≥70 years compared to <70 years conferred inferior OS (HR 3.08; 95% CI, 2.64-3.59; P < 0.01). CONCLUSIONS: Our study confirmed improved survival outcomes for patients of higher socio-economic status and younger age. Future research to explain the unexpected survival benefit in patients who lived in more remote areas should examine factors including the correlation between geographical residence and eventual treatment facility as well as compare the BSWR care model to other regions' approaches.

Rheumatoid arthritis and incident fracture in women: a case-control study.

BACKGROUND: To examine fracture incidence in women with rheumatoid arthritis (RA) for an entire geographical region of south-eastern Australia. METHODS: Women aged 35 years and older, resident in the Barwon Statistical Division (BSD) and clinically diagnosed with RA 1994-2001 were eligible for inclusion as cases (n = 1,008). The control population (n = 172,422) comprised the entire female BSD population aged 35 years and older, excluding those individuals identified as cases. Incident fractures were extracted from the prospective Geelong Osteoporosis Study Fracture Grid. We calculated rate ratios (RR) and 95% confidence intervals (CI) to compare the age-adjusted rate of fracture between the RA and non-RA populations, and used a chi-square test to compare proportions of fractures between women with and without RA, and a two-sided Mann-Whitney U-test to examine age-differences. RESULTS: Among 1,008 women with RA, 19 (1.9%) sustained a fracture, compared to 1,981 fractures sustained by the 172,422 women without RA (1.2%). Fracture rates showed a trend for being greater among women diagnosed with RA (age-adjusted RR 1.43, 95%CI 0.98-2.09, p = 0.08). Women with RA sustained vertebral fractures at twice the expected frequency, whereas hip fractures were underrepresented in the RA population (p < 0.001). RA status was not associated with the likelihood of sustaining a fracture at sites adjacent to joints most commonly affected by RA (p = 0.22). CONCLUSION: Given that women with RA have a greater risk of fracture compared to women without RA, these patients may be a suitable target population for anti-resorptive agents; however, larger studies are warranted.

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.

Characteristics of cancer diagnoses and staging in South Western Victoria: a rural perspective.

OBJECTIVE: Australian states and territories have legislation mandating reporting of cancer diagnoses; however, tumour stage at diagnosis, treatment plan and associated outcomes are not routinely recorded in cancer registries for all tumour types. This study describes the Evaluation of Cancer Outcomes study that collects detailed information for patients diagnosed with cancer in south-western Victoria. DESIGN: Retrospective data collection. SETTING: Population based. PARTICIPANTS: New cancer patients within the Barwon South Western region. MAIN OUTCOME MEASURES: Cancer incidence and staging data for a regional and rural area. RESULTS: In 2009, there were 1778 primary tumours. Prominent tumour streams included prostate, breast, colon, lung, lymphoma, melanoma and rectum. Stage at diagnosis was recorded for more than 50% of patients for the tumour streams of testis, breast, bowel, renal, lung, and head and neck. Patients reporting to health centres with an on-site oncologist as part of their team had a higher rate of staging recorded at diagnosis (48.0 versus 36.9%, P=0.01). More women (55.4%) than men (41.4%) had stage-recorded. CONCLUSION: The Evaluation of Cancer Outcomes study is an important initiative that collects information about newly diagnosed cases of cancer more detailed than is currently collected by the Cancer Council of Victoria. Future studies will build on this base dataset and provide valuable insight into the regional and rural experience of treatment pathways after diagnosis. More work is needed to bring more services to our rural patients, or more education is needed to encourage the recording of tumour staging.

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.

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.

Fracture risk score and absolute risk of fracture.

PURPOSE: To report the 5- and 10-year absolute risk of fracture associated with the previously reported fracture risk (FRISK) score. MATERIALS AND METHODS: All participants gave written, informed consent, and the Barwon Health Human Research Ethics Committee approved the study. An age-stratified population-based sample of women aged 60 years and older (n = 600) was recruited during 1994-1996. FRISK scores of 0-10 incorporating bone mineral density (BMD) at two sites (hip and spine), falls scores in the previous 12 months of 1-4, weight, and number of fractures as an adult were calculated. Fractures of the hip, spine, humerus, and wrist were ascertained during a median follow-up period of 9.6 years (interquartile range, 6.6-10.5). The cumulative probability of fracture at 5 and 10 years after baseline measurements was calculated by using actuarial methods. The utility of this model was compared with other FRISK algorithms, including the World Health Organization FRISK assessment tool FRAX designed for United Kingdom and that designed for the United States and the Garvan nomogram (Australia). RESULTS: This study supplies the 5- and 10-year absolute risk of fracture associated with all levels of the FRISK score. While there are modest differences in absolute risk of fracture seen for different numbers of prior fractures, the more marked differences occur across the different categories of falls scores and different categories of BMD. The receiver operating characteristic curves showed no significant difference in area under the curve for all four absolute risk of fracture algorithms. CONCLUSION: Absolute risk of fracture can be determined by using readily obtainable clinical information that may aid treatment decisions.

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.

Association between radioiodine therapy for Graves' hyperthyroidism and thyroid-associated ophthalmopathy.

To investigate the role of radioactive iodine (RAI) in the onset and progression of thyroid-associated ophthalmopathy (TAO). Forty-six Graves' disease patients with mild or no ophthalmopathy were prospectively treated with carbimazole (CBZ) (n = 22) or RAI (n = 24). Treatment effects were evaluated clinically over 12 months, and with orbital MRI-measured extra-ocular muscle (EOM) volumes at baseline and at 6 months. The diagnosis of TAO was based on the clinical activity score (CAS) system. There were 11/22 CBZ and 10/24 RAI patients with active ophthalmopathy at baseline. Despite greater mean TSH levels post-RAI (P = 0.003), there was no increase in the likelihood of developing active ophthalmopathy (OR 0.95; 95% CI 0.56-1.61, P = 0.9) or EOM dysfunction (OR 0.52; 95% CI 0.26-1.06, P = 0.074). The increased mean palpebral aperture post-RAI (P = 0.023) and greater mean proptosis in the CBZ group (P = 0.005) were not confirmed when the absolute values of these measurements were examined. There was no association between the treatment received and MRI-measured EOM volumes. In this study, RAI therapy for Graves' disease did not increase the risk of progression or development of ophthalmopathy in patients with mild or no eye disease at baseline.

Depression and bone metabolism. A review.

BACKGROUND: There are data to suggest low bone mineral density is disproportionately prevalent among those with psychiatric disorders. This paper aims to review the current evidence on the relationship between depression and bone mineral density, and identify potential mechanisms. METHODS: Relevant sources were identified from the Pubmed and Web of Science (ISI) databases from the first relevant publication in 1994 to the present, 2007, using a combination of key words and terms including depression, major depressive disorder, osteoporosis, bone mineral density, hypothalamic-pituitary-adrenal axis, cortisol, cytokines, leptin, antidepressants, selective serotonin reuptake inhibitors, smoking, alcohol, physical activity and diet. Reference lists of chosen articles were further reviewed for associated publications. RESULTS: The possible association between psychiatric illness, in particular depression, and osteoporosis has been the subject of a growing body of research yielding various findings, although most identify some effect on bone. In addition to medication-related processes and/or modifiable lifestyle factors associated with mood disturbances, endocrine and immune alteration secondary to depression may play a pathogenetic role in bone metabolism. CONCLUSIONS: Additional longitudinal studies, with the advantage of temporal sequencing, remain to be conducted, as well as research into potential mechanisms surrounding the association. Nevertheless, the current findings are of clinical relevance, given the health burden of both depression and osteoporosis.

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.

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.

Leptin in depressed women: cross-sectional and longitudinal data from an epidemiologic study.

BACKGROUND: There is conflicting evidence regarding levels of leptin in depression. In this study we aimed to investigate the relationship between serum leptin level and depression in a community sample of women using both cross-sectional and longitudinal data. METHODS: From among 510 women aged 20-78 yr, 83 were identified with a lifetime history of major depressive disorder or dysthymia, ascertained using the Structured Clinical Interview for DSM-IV-TR Research Version, Non-patient edition (SCID-I/NP). Serum leptin levels were measured by radioimmunoassay. Medication use and lifestyle were self-reported and body mass index (BMI) determined from measures of height and weight. RESULTS: Using multiple linear regression, serum leptin levels were greater among women with a lifetime history of depression compared to women without any history of depression, independent of BMI. Adjusted geometric mean values of serum leptin were 16.37 (95%CI 14.70-18.23) ng/mL for depressed and 14.46 (95%CI 13.79-15.16) ng/mL for non-depressed women (P=0.039). The hazard ratio (HR) for a de novo depressive disorder over five years increased 2.56-fold for each standard deviation increase in log-transformed serum leptin among non-smokers and this was not explained by differences in BMI, medications or other lifestyle factors (HR=2.56, 95%CI 1.52-4.30). No association was observed for smokers. LIMITATIONS: There is potential for unrecognised confounding, recall bias and transient changes in body composition. CONCLUSION: Women with a lifetime history of depression have elevated levels of serum leptin, and elevated serum leptin predicts subsequent development of a depressive disorder.

Selective serotonin reuptake inhibitor use and bone mineral density in women with a history of depression.

Selective serotonin reuptake inhibitors (SSRIs) are a first-line treatment for depression. They have been reported to regulate serotonin signalling in bone cells and may influence bone metabolism. This study aimed to investigate the effect of SSRIs on bone mineral density (BMD) in a sample of women with a lifetime history of depression. In this community-based study of 607 women, a history of depression was ascertained using the structured clinical interview for Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV-TR research version, non-patient edition. BMD was measured at the posterior-anterior (PA) spine, hip, total body and forearm using dual energy absorptiometry, and medication use and lifestyle factors were self-reported. Among 177 women with a lifetime history of depression, current users of bisphosphonates, glucocorticoids, hormone therapy and antidepressants other than SSRIs were excluded. Of the remaining 128 (median age 51.5 years, range 30-74), 26 (20.3%) reported current SSRI use. After controlling for age, weight, height and smoking history, BMD among SSRI users was 5.6% lower at the femoral neck (P=0.03), 6.2% lower at the trochanter (P=0.04) and 4.4% lower at the mid-forearm (P=0.03) than nonusers. No differences in BMD were detected at other sites. Although the mechanism remains unclear, these observations are consistent with a role for the serotonergic system in regulating bone metabolism.

Application of epidemiology to change health policy: defining age-related thresholds of bone mineral density for primary prevention of fracture.

In Australia, benefits for antifracture therapies have been available for patients with osteoporosis and a prior fracture. No benefits were available to those with no prior fracture. We aimed to define, in women with no prior fracture, age-related thresholds of bone mineral density (BMD) associated with fracture risk equivalent to that of women with prior fracture and osteoporosis. A case-control study of women (> or =50 yr) was conducted, including 291 fracture cases and 823 controls. BMD was measured at the proximal femur and posterior anterior (PA) spine. A fracture risk score (FRS) for the group with no prior fracture was calculated with discriminant analysis. The thresholds for equivalent fracture risk between those with no prior fracture and those with prior fracture were assessed using logistic regression. Increasing the FRS to +0.98 in women with no prior fracture resulted in equivalent odds of sustaining a fracture to those with prior fracture and osteoporosis. The corresponding T-score thresholds at the spine were -4.6 at 50 yr, -3.9 at 60 yr, -3.1 at 70 yr, and -2.4 at 80 yr. The femoral neck T-score thresholds were lower by 0.5 standard deviation. The high-risk individuals defined by this study should be considered for primary fracture prevention therapy.

Half the burden of fragility fractures in the community occur in women without osteoporosis. When is fracture prevention cost-effective?

To determine the age- and BMD-specific burden of fractures in the community and the cost-effectiveness of targeted drug therapy, we studied a demographically well-categorized population with a single main health provider. Of 1224 women over 50 years of age sustaining fractures during 2 years, the distribution of all fractures was 11%, 20%, 33%, and 36% in those aged 50-59, 60-69, 70-79, and 80+ years, respectively. Osteoporosis (T score < -2.5) was present in 20%, 46%, 59%, and 69% in the respective age groups. Based on this sample and census data for the whole country, treating all women over 50 years of age in Australia with a drug that halves fracture risk in osteoporotic women and reduces fractures in those without osteoporosis by 20%, was estimated to prevent 18,000 or 36% of the 50,000 fractures per year at a total cost of $573 million (AUD). Screening using a bone mineral density of T score of -2.5 as a cutoff, misses 80%, 54%, 41%, and 31% of fractures in women in the respective age groups. An analysis of cost per averted fracture by age group suggests that treating women in the 50- to 59-year age group with osteoporosis alone costs $156,400 per averted fracture. However, in women aged over 80 years, the cost per averted fracture is $28,500. We infer that treating all women over 50 years of age is not feasible. Using osteoporosis and age (>60 years) as criteria for intervention reduces the population burden of fractures by 28% and is cost-effective but solutions to the prevention of the remaining 72% of fragility fractures remain unavailable.

Antioxidant vitamin supplements and markers of bone turnover in a community sample of nonsmoking women.

BACKGROUND: Whereas several epidemiological studies suggest that low dietary intake of vitamins C and E is linked to increased hip fracture in smokers and antioxidants (dietary and endogenous) are reduced in elderly osteoporotic women, none has demonstrated an effect of supplemental antioxidants on bone turnover. METHODS: In an observational study of 533 randomly selected women, we investigated the associations among the use of antioxidant supplements, vitamins C and E, serum levels of biochemical markers of bone turnover (C-telopeptide [CTx] and bone-specific alkaline phosphatase [BSAP]), and whole body bone mineral density (BMD). RESULTS: Twenty-two women were identified as current users of supplemental vitamin C or E. Duration of antioxidant supplement use was negatively associated with age-adjusted and weight-adjusted serum CTx, such that mean CTx levels (natural log transformed) were 0.022 units lower for each year of exposure. No significant differences were detected for adjusted serum BSAP or whole body BMD. CONCLUSIONS: Our results suggest that antioxidant vitamin E or C supplements may suppress bone resorption in nonsmoking postmenopausal women. Coupling of bone formation and resorption may explain the absence of an effect on bone formation markers, given evidence of enhanced effects of antioxidants on osteoblast differentiation; this warrants further investigation. This work adds to the growing body of evidence that antioxidants may play a role in preventing osteoporosis.