Sex differences in recovery of quality of life 12 months post-fracture in community-dwelling older adults: analyses of the Australian arm of the International Costs and Utilities Related to Osteoporotic Fractures Study (AusICUROS).

In this study of 695 Australian older adults (aged ≥50 years), we found that men and women had a similar trajectory of health-related quality of life (HRQoL) recovery following fragility fracture at any skeletal site. These results provide us with critical knowledge that improves our understanding of health outcomes post-fracture. INTRODUCTION: Mortality is higher in men than that in women following a fragility fracture, but it is unclear whether recovery of patient-reported outcomes such as health-related quality of life (HRQoL) differs between sexes. This study aimed to identify sex differences in HRQoL recovery 12 months post-fracture. METHODS: Data were from the Australian arm of the International Costs and Utilities Related to Osteoporotic Fractures Study (AusICUROS). Participants recruited to AusICUROS were adults aged ≥50 years who sustained a fragility fracture. HRQoL was measured using the EQ-5D-3L at three time-points post-fracture: within 2 weeks (including pre-fracture recall) and at 4 and 12 months. Multivariate logistic regression analyses were undertaken, adjusting for confounders including age, education, income, and healthcare utilization post-fracture. RESULTS: Overall, 695 AusICUROS participants (536 women, 77.1%) were eligible for analysis with fractures at the hip (n = 150), distal forearm (n = 261), vertebrae (n = 61), humerus (n = 52), and other skeletal sites (n = 171). At the time of fracture, men were younger, reported a higher income, and were more likely to be employed, compared with women. For all fracture sites combined, there were no differences between men and women in recovery to pre-fracture HRQoL at 12-month follow-up (adjusted OR = 1.09; 95% CI: 0.75-1.61). When stratified by fracture site, no significant sex differences were seen for hip (OR = 1.02; 95% CI: 0.42-2.52), distal forearm (OR = 1.60; 95% CI: 0.68-3.78), vertebral (OR = 2.28; 95% CI: 0.61-8.48), humeral (OR = 1.62; 95% CI: 0.16-9.99), and other fractures (OR = 1.00; 95% CI: 0.44-2.26). CONCLUSION: Community-dwelling men and women who survived the 12 months following fragility fracture had a similar trajectory of HRQoL recovery at any skeletal site.

How well do the FRAX (Australia) and Garvan calculators predict incident fractures? Data from the Geelong Osteoporosis Study.

This study reports that both FRAX and Garvan calculators underestimated fractures in Australian men and women, particularly in those with osteopenia or osteoporosis. Major osteoporotic fractures were poorly predicted, while both calculators performed acceptably well for hip fractures. INTRODUCTION: This study assessed the ability of the FRAX (Australia) and Garvan calculators to predict fractures in Australian women and men. METHODS: Women (n = 809) and men (n = 821) aged 50-90 years, enrolled in the Geelong Osteoporosis Study, were included. Fracture risk was estimated using FRAX and Garvan calculators with and without femoral neck bone mineral density (BMD) (FRAXBMD, FRAXnoBMD, GarvanBMD, GarvannoBMD). Incident major osteoporotic (MOF), fragility, and hip fractures over the following 10 years were verified radiologically. Differences between observed and predicted numbers of fractures were assessed using a chi-squared test. Diagnostics indexes were calculated. RESULTS: In women, 115 MOF, 184 fragility, and 42 hip fractures occurred. For men, there were 73, 109, and 17 fractures, respectively. FRAX underestimated MOFs, regardless of sex or inclusion of BMD. FRAX accurately predicted hip fractures, except in women with BMD (20 predicted, p = 0.004). Garvan underestimated fragility fractures except in men using BMD (88 predicted, p = 0.109). Garvan accurately predicted hip fractures except for women without BMD (12 predicted, p < 0.001). Fractures were underestimated primarily in the osteopenia and osteoporosis groups; MOFs in the normal BMD group were only underestimated by FRAXBMD and fragility fractures by GarvannoBMD, both in men. AUROCs were not different between scores with and without BMD, except for fragility fractures predicted by Garvan in women (0.696, 95% CI 0.652-0.739 and 0.668, 0.623-0.712, respectively, p = 0.008) and men, which almost reached significance (0.683, 0.631-0.734, and 0.667, 0.615-0.719, respectively, p = 0.051). Analyses of sensitivity and specificity showed overall that MOFs and fragility fractures were poorly predicted by both FRAX and Garvan, while hip fractures were acceptably predicted. CONCLUSIONS: Overall, the FRAX and Garvan calculators underestimated MOF and fragility fractures, particularly in individuals with osteopenia or osteoporosis. Hip fractures were predicted better by both calculators. AUROC analyses suggest that GarvanBMD performed better than GarvannoBMD for prediction of fragility fractures.

Diversity in fall characteristics hampers effective prevention: the precipitants, the environment, the fall and the injury.

Falls among the elderly are common and characteristics may differ between injurious and non-injurious falls. Among 887 older Australian women followed for 1.6 years, 32% fell annually. Only 8.5% resulted in fracture and/or hospital admission. The characteristics of those falls are indistinguishable from those not coming to medical attention. INTRODUCTION: The precipitants and environment of all falls occurring among a large cohort of older Caucasian women were categorised by injury status to determine if the characteristics differed between injurious and non-injurious falls. METHODS: Among 887 Australian women (70+ years), falls were ascertained using monthly postcard calendars and a questionnaire was administered for each fall. Hospital admissions and fractures were independently confirmed. RESULTS: All falls were reported for a mean observation time of 577 (IQR 546-607) days per participant, equating to a total 1400 person-years. Thirty-two percent fell at least once per year. The most common features of a fall were that the faller was walking (61%) at home (61%) during the day (88%) and lost balance (32%). Only 12% of all falls occurred at night. Despite no difference in the type of injury between day and night, the likelihood of being hospitalised from a fall at night was 4.5 times greater than that of a daytime fall with adjustment for injury type and participant age (OR 4.5, 95% CI 2.1, 9.5; p < 0.001). Of all falls, approximately one third were associated with no injury to the faller (31%), one third reported a single injury (37%) and one third reported more than one injury (32%). In 95% of falls, the faller was not admitted to hospital. Only 5% of falls resulted in fracture(s). CONCLUSIONS: Our findings demonstrate the significant diversity of precipitants and environment where falls commonly occur among older community-dwelling women. Falls resulting in fracture and/or hospital admission collectively represent 8.5% of all falls and their characteristics are indistinguishable from falls not coming to medical attention and incurring no apparent cost to the health system.

The nasal mucosal late allergic reaction to grass pollen involves type 2 inflammation (IL-5 and IL-13), the inflammasome (IL-1ß), and complement.

Non-invasive mucosal sampling (nasosorption and nasal curettage) was used following nasal allergen challenge with grass pollen in subjects with allergic rhinitis, in order to define the molecular basis of the late allergic reaction (LAR). It was found that the nasal LAR to grass pollen involves parallel changes in pathways of type 2 inflammation (IL-4, IL-5 and IL-13), inflammasome-related (IL-1ß), and complement and circadian-associated genes. A grass pollen nasal spray was given to subjects with hay fever followed by serial sampling, in which cytokines and chemokines were measured in absorbed nasal mucosal lining fluid, and global gene expression (transcriptomics) assessed in nasal mucosal curettage samples. Twelve of 19 subjects responded with elevations in interleukin (IL)-5, IL-13, IL-1ß and MIP-1ß/CCL4 protein levels in the late phase. In addition, in these individuals whole-genome expression profiling showed upregulation of type 2 inflammation involving eosinophils and IL-4, IL-5 and IL-13; neutrophil recruitment with IL-1α and IL-1ß; the alternative pathway of complement (factor P and C5aR); and prominent effects on circadian-associated transcription regulators. Baseline IL-33 mRNA strongly correlated with these late-phase responses, whereas a single oral dose of prednisone dose-dependently reversed most nasal allergen challenge-induced cytokine and transcript responses. This study shows that the LAR to grass pollen involves a range of inflammatory pathways and suggests potential new biomarkers and therapeutic targets. Furthermore, the marked variation in mucosal inflammatory events between different patients suggests that in the future precision mucosal sampling may enable rational specific therapy.

Anxiety disorders and falls among older adults.

BACKGROUND: Falls are common among older adults and can lead to serious injuries, including fractures. We aimed to determine associations between anxiety disorders and falls in older adults. METHODS: Participants were 487 men and 376 women aged ≥60 years enrolled in the Geelong Osteoporosis Study, Australia. Using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Non-patient edition (SCID-I/NP), lifetime history of anxiety disorders was determined. Falls were determined by self-report. In men, a falls-risk score (Elderly Falls Screening Test (EFST)) was also calculated. RESULTS: Among fallers, 24 of 299 (8.0%) had a lifetime history of anxiety disorder compared to 36 of 634 (5.7%) non-fallers (p=0.014). Examination of the association between anxiety and falls suggested differential relationships for men and women. In men, following adjustment for psychotropic medications, mobility and blood pressure, lifetime anxiety disorder was associated with falling (OR 2.96; 95%CI 1.07-8.21) and with EFST score (OR 3.46; 95%CI 1.13-10.6). In women, an association between lifetime anxiety disorder and falls was explained by psychotropic medication use, poor mobility and socioeconomic status. LIMITATIONS: Sub-group analyses involving types of anxiety and anxiety disorders over the past 12-months were not performed due to power limitations. CONCLUSION: Although anxiety disorders were independently associated with a 3-fold increase in likelihood of reported falls and high falls risk among men, an independent association was not detected among women. These results may aid in prevention of falls through specific interventions aimed at reducing anxiety, particularly in men.

A novel flow cytometric-based method to measure kinase inhibition in sputum from COPD subjects.

INTRODUCTION: Janus kinases (JAKs) regulate inflammatory gene expression through phosphorylation of signal transducer and activator of transcription (STAT) proteins. Expression of STAT proteins is increased in chronic obstructive pulmonary disease (COPD), and may be involved in driving chronic inflammation. Oral JAK inhibitors are effective as anti-inflammatory therapy but exhibit dose-limiting adverse effects. Development of inhaled compounds would be enhanced by robust biomarkers that directly reflect the anti-inflammatory and pharmacological activity in the lung. METHODS: A novel flow cytometry assay was developed to measure STAT1 phosphorylation in sputum inflammatory cells. The standard sputum processing method was refined to improve sputum cell viability. The flow cytometric assay was used to assess the reproducibility of the measurement of STAT1 phosphorylation and the in vitro activity of a pan JAK-inhibitor on three separate visits in patients with COPD. RESULTS: Upregulation of STAT1 phosphorylation was measured following in vitro IFNγ stimulation of sputum macrophages (stimulated/unstimulated ratio 1.57; p<0.00001). Upregulation was inhibited following in vitro preincubation with a pan JAK-inhibitor (inhibited+stimulated/unstimulated ratio 0.97). STAT1 phosphorylation activity could only be measured in macrophages. CONCLUSIONS: Sputum from patients with COPD can be used to reproducibly measure phospho-STAT expression in sputum macrophages. The flow cytometry-based method can be used to evaluate kinase inhibitors in vitro and subsequently in ex vivo studies. The assay is particularly useful for the assessment of inhaled compounds where whole blood assays may not be relevant.

Citalopram and sertraline exposure compromises embryonic bone development.

Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed treatments for depression and, as a class of drugs, are among the most used medications in the world. Concern regarding possible effects of SSRI treatment on fetal development has arisen recently as studies have suggested a link between maternal SSRI use and an increase in birth defects such as persistent pulmonary hypertension, seizures and craniosynostosis. Furthermore, SSRI exposure in adults is associated with decreased bone mineral density and increased fracture risk, and serotonin receptors are expressed in human osteoblasts and osteoclasts. To determine possible effects of SSRI exposure on developing bone, we treated both zebrafish, during embryonic development, and human mesenchymal stem cells (MSCs), during differentiation into osteoblasts, with the two most prescribed SSRIs, citalopram and sertraline. SSRI treatment in zebrafish decreased bone mineralization, visualized by alizarin red staining and decreased the expression of mature osteoblast-specific markers during embryogenesis. Furthermore, we showed that this inhibition was not associated with increased apoptosis. In differentiating human MSCs, we observed a decrease in osteoblast activity that was associated with a decrease in expression of the osteoblast-specific genes Runx2, Sparc and Spp1, measured with quantitative real-time PCR (qRT-PCR). Similar to the developing zebrafish, no increase in expression of the apoptotic marker Caspase 3 was observed. Therefore, we propose that SSRIs inhibit bone development by affecting osteoblast maturation during embryonic development and MSC differentiation. These results highlight the need to further investigate the risks of SSRI use during pregnancy in exposing unborn babies to potential skeletal abnormalities.

Non-hip and non-vertebral fractures: the neglected fracture sites.

SUMMARY: Non-hip, non-vertebral fractures (NHNVF) were compared with hip, vertebral and controls. NHNVF were younger and heavier than controls and hip/vertebral fractures in both men and women, respectively. Falls and prior fractures were less common in NHNVF than hip fractures. Glucocorticoid use was lower in NHNVF compared to vertebral fracture (VF) in men. INTRODUCTION: Although hip fracture (HF) and vertebral fractures (VF) receive the most attention in the literature and are the targeted sites for fracture prevention, non-hip, non-vertebral fracture (NHNVF) sites account for a greater proportion of fractures than the hip or vertebrae. This study aimed to assess risk factors for NHNVF and compare them with those for HF, VF and controls. METHODS: Incident fractures during 2005-2007 for men and 1994-1996 for women were identified using computerised keyword searches of radiological reports, and controls were selected at random from electoral rolls for participation in the Geelong Osteoporosis Study. Participants aged 60+ years were included in this study. RESULTS: Compared to controls, men and women with NHNVF were younger (ORs, 0.90, 95% CI 0.86-0.94; and 0.96, 0.93-0.98, respectively) and had a lower femoral neck bone mineral density (BMD) T-score (age-adjusted; difference [men] 0.383, P = 0.002; [women] 0.287, P = 0.001). Compared to HF, men and women with NHNVF were heavier (difference [men] 9.0 kg, P = 0.01; [women] 7.6 kg, P < 0.001). Heavier weight was also a risk factor for women with NHNVF compared to VF (1.03, 1.01-1.06). In men with NHNVF, falls (0.37, 0.14-0.97) and prior fractures (0.38, 0.15-0.98) were less common compared to HF; and glucocorticoid use was less common for NHNVF (0.30, 0.11-0.85) compared to VF. CONCLUSIONS: Given the high numbers of NHNVF sustained by men and women in this study, fracture prevention strategies should focus on individuals with high risk of sustaining these types of fractures, as well as on individuals who are more likely to sustain a HF or VF.

Bronchoabsorption; a novel bronchoscopic technique to improve biomarker sampling of the airway.

BACKGROUND: Current techniques used to obtain lung samples have significant limitations and do not provide reproducible biomarkers of inflammation. We have developed a novel technique that allows multiple sampling methods from the same area (or multiple areas) of the lung under direct bronchoscopic vision. It allows collection of mucosal lining fluid and bronchial brushing from the same site; biopsy samples may also be taken. The novel technique takes the same time as standard procedures and can be conducted safely. METHODS: Eight healthy smokers aged 40-65 years were included in this study. An absorptive filter paper was applied to the bronchial mucosa under direct vision using standard bronchoscopic techniques. Further samples were obtained from the same site using bronchial brushings. Bronchoalveolar lavage (BAL) was obtained using standard techniques. Chemokine (C-C Motif) Ligand 20 (CCL20), CCL4, CCL5, Chemokine (C-X-C Motif) Ligand 1 (CXCL1), CXCL8, CXCL9, CXCL10, CXCL11, Interleukin 1 beta (IL-1ß), IL-6, Vascular endothelial growth factor (VEGF), Matrix metalloproteinase 8 (MMP-8) and MMP-9 were measured in exudate and BAL. mRNA was collected from the bronchial brushings for gene expression analysis. RESULTS: A greater than 10 fold concentration of all the biomarkers was detected in lung exudate in comparison to BAL. High yield of good quality RNA with RNA integrity numbers (RIN) between 7.6 and 9.3 were extracted from the bronchial brushings. The subset of genes measured were reproducible across the samples and corresponded to the inflammatory markers measured in exudate and BAL. CONCLUSIONS: The bronchoabsorption technique as described offers the ability to sample lung fluid direct from the site of interest without the dilution effects caused by BAL. Using this method we were able to successfully measure the concentrations of biomarkers present in the lungs as well as collect high yield mRNA samples for gene expression analysis from the same site. This technique demonstrates superior sensitivity to standard BAL for the measurement of biomarkers of inflammation. It could replace BAL as the method of choice for these measurements. This method provides a systems biology approach to studying the inflammatory markers of respiratory disease progression. TRIAL REGISTRATION: NHS Health Research Authority (13/LO/0256).

Changes in quality of life associated with fragility fractures: Australian arm of the International Cost and Utility Related to Osteoporotic Fractures Study (AusICUROS).

UNLABELLED: We investigated change in health-related quality of life due to fracture in Australian adults aged over 50 years. Fractures reduce quality of life with the loss sustained at least over 12 months. At a population level, the loss was equivalent to 65 days in full health per fracture. PURPOSE: We aimed to quantify the change in health-related quality of life (HRQoL) that occurred as a consequence of a fracture using the EQ-5D-3 L questionnaire. METHODS: Adults aged ≥50 years with a low to moderate energy fracture were recruited from eight study centres across Australia. This prospective study included an 18-month follow-up of participants recruited within 2 weeks of a fracture (hip, wrist, humerus, vertebral and ankle). Information collected at baseline and 4, 12 and 18 months included characteristics of participants such as income level, education and prior fracture status. At 12 months post-fracture, the cumulative loss of quality of life was estimated using multivariate regression analysis to identify the predictors of HRQoL loss. RESULTS: Mean HRQoL for all participants before fracture was 0.86, with wrist fracture having the highest pre-fracture HRQoL (0.90), while vertebral fracture had the lowest (0.80). HRQoL declined to 0.42 in the immediate post-fracture period. Only participants with a wrist, humerus or ankle fracture returned to their pre-fracture HRQoL after 18 months. An increased loss of HRQoL over 12 months was associated with HRQoL prior to the fracture, hospitalisation, education and fracture site. The multiple regression explained 30 % of the variation in the cumulative HRQoL loss at 12 months post-fracture for all fractures. CONCLUSION: Low to moderate energy fractures reduce HRQoL, and this loss is sustained for at least 12 months or, in the case of hip and spine fractures, at least 18 months. At a population level, this represents an average loss of 65 days in full health per fragility fracture. This significant burden reinforces the need for cost-effective fracture prevention strategies.

Fracture risk among older men: osteopenia and osteoporosis defined using cut-points derived from female versus male reference data.

SUMMARY: We explored the effect of using male and female reference data in a male sample to categorise areal bone mineral density (BMD). Using male reference data, a large proportion of fractures arose from osteopenia, whereas using female reference data shifted the fracture burden into normal BMD. INTRODUCTION: The purpose of this study was to describe fracture risk associated with osteopenia and osteoporosis in older men, defined by areal BMD and using cut-points derived from male and female reference data. METHODS: As part of the Geelong Osteoporosis Study, we followed 619 men aged 60-93 years after BMD assessments (performed 2001-2006) until 2010, fracture, death or emigration. Post-baseline fractures were radiologically confirmed, and proportions of fractures in each BMD category were age-standardised to national profiles. RESULTS: Based on World Health Organization criteria, and using male reference data, 207 men had normal BMD at the femoral neck, 357 were osteopenic and 55 were osteoporotic. Using female reference data, corresponding numbers were 361, 227 and 31. During the study, 130 men died, 15 emigrated and 63 sustained at least one fracture. Using male reference data, most (86.5 %) of the fractures occurred in men without osteoporosis on BMD criteria (18.4 % normal BMD, 68.1 % osteopenia). The pattern differed when female reference data were used; while most fractures arose from men without osteoporosis (88.2 %), the burden shifted from those with osteopenia (34.8 %) to those with normal BMD (53.4 %). CONCLUSIONS: Decreasing BMD categories defined increasing risk of fracture. Although men with osteoporotic BMD were at greatest risk, they made a relatively small contribution to the total burden of fractures. Using male reference data, two-thirds of the fractures arose from men with osteopenia. However, using female reference data, approximately half of the fractures arose from those with normal BMD. Using female reference data to define osteoporosis in men does not appear to be the optimal approach.

Associations between measures of adiposity over 10 years and patella cartilage in population-based asymptomatic women.

OBJECTIVE: Osteoarthritis (OA) most commonly affects the patellofemoral compartment of the knee, and is a major cause of pain and disability. Structural changes that evolve prior to the onset of symptoms can be visualised using magnetic resonance imaging (MRI). There is little known information about the role of adiposity on the early structural changes in the patella cartilage in younger, asymptomatic adult females. METHODS: One hundred and sixty asymptomatic women (20-49 years) participating in the Geelong Osteoporosis Study underwent knee MRI (2006-8). Weight and body mass index (BMI) were measured 10 years prior (1994-7, baseline) and at the time of MRI (current), with change over the period calculated (current-baseline). Relationships between measures of adiposity and patella cartilage volume and defects were examined. RESULTS: After adjustment for age and patella bone volume, there was a reduction of 13 ml (95% confidence interval (95% CI), -25.7, -0.55) in patella cartilage volume for every 1 unit increase in current BMI, and a reduction of 27 ml (95% CI -52.6, -1.5) per BMI unit increase over 10 years (P=0.04 for both). No significant association was observed between baseline BMI and patella cartilage volume (P=0.16). Increased baseline and current weight and BMI were associated with increased prevalence of patella cartilage defects (all P<0.001). CONCLUSIONS: Adiposity and weight gain during midlife are associated with detrimental structural change at the patella in young to middle-aged healthy non-osteoarthritic women. Maintaining a healthy weight and avoiding weight gain in younger asymptomatic women may be important in the prevention of patellofemoral OA.

Calcaneal ultrasound reference ranges for Australian men and women: the Geelong Osteoporosis Study.

UNLABELLED: Heel ultrasound is a more portable modality for assessing fracture risk than dual-energy X-ray absorptiometry and does not use ionising radiation. Fracture risk assessment requires appropriate reference data to enable comparisons. This study reports the first heel ultrasound reference ranges for the Australian population. INTRODUCTION: This study aimed to develop calcaneal (heel) ultrasound reference ranges for the Australian adult population using a population-based random sample. METHODS: Men and women aged≥20 years were randomly selected from the Barwon Statistical Division in 2001-2006 and 1993-1997, respectively, using the electoral roll. Broadband ultrasound attenuation (BUA), speed of sound (SOS) and stiffness index (SI) were measured at the heel using a Lunar Achilles Ultrasonometer. Gender-specific means and standard deviations for BUA, SOS and SI were calculated for the entire sample (men 20-93 years, n=1,104; women 20-92 years, n=914) and for participants aged 20-29 years (men, n=157; women, n=151). Associations between ultrasound measures and age were examined using linear regression. RESULTS: For men, mean±standard deviation BUA, SOS and SI were 118.7±15.8 dB/MHz, 1,577.0±43.7 m/s and 100.5±20.7, respectively; values for women were consistently lower (111.0±16.4 dB/MHz, P<0.001; 1,571.0±39.0 m/s, P=0.001; and 93.7±20.3, P<0.001, respectively). BUA was higher in young men compared with young women (124.5±14.4 vs 121.0±15.1 dB/MHz), but SOS (1,590.1±43.1 vs 1,592.5±35.0 m/s) and SI (108.0±19.9 vs 106.3±17.7) were not. The relationships between age and each ultrasound measure were linear and negative across the age range in men; associations were also negative in women but non-linear. CONCLUSION: These data provide reference standards to facilitate the assessment of fracture risk in an Australian population using heel ultrasound.

Bone mineral density is cross sectionally associated with cartilage volume in healthy, asymptomatic adult females: Geelong Osteoporosis Study.

INTRODUCTION: The association between osteoporosis and osteoarthritis (OA) is controversial. Although previous studies have shown total body, lower limb, spinal and knee BMD and knee cartilage volume to be positively associated, the relationship between other distant site-specific measures of BMD and other knee structures is unknown. The aim of this study was to determine the associations between BMD at eight skeletal sites, and knee structure in asymptomatic young to middle-aged females without any clinical signs of OA. METHODS: One hundred and sixty healthy, asymptomatic females (29-50 yr) underwent magnetic resonance imaging of the knee. BMD was measured at the spine, hip, total body and forearm by dual energy X-ray absorptiometry, and at the calcaneus by quantitative ultrasound. BMD was tested for an association with cartilage volume, defects, and bone marrow lesions (BMLs). RESULTS: Medial cartilage volume was positively associated with BMD at the spine, total body, femoral neck, and Ward's triangle (all p<0.05), with non-significant associations in the same direction at the trochanter (p=0.07). Findings in the lateral compartment were similar. The presence of medial cartilage knee defects were also associated with BMD at the spine; defects in the lateral compartment were associated with BMD at the forearm (both p=0.05). BMD was not associated with the presence of BMLs. No associations were observed with calcaneus BMD. CONCLUSIONS: Site-specific BMD is associated with cartilage volume at the knee in asymptomatic young to middle-aged adults, with the direction and effects trending in the same direction. The magnitude of changes correlates with clinically relevant changes. QUS defined calcaneus BMD, showed no associations with knee structure. Although systemic factors may underlie the association between knee cartilage volume and axial/lower limb BMD, these data suggest that common local, possibly biomechanical factors may also play a role.

Incident hip fracture and social disadvantage in an Australian population aged 50 years or greater.

AIMS: There is an inverse association between socioeconomic status (SES) and most causes of morbidity. Hip fractures pose a significant public health burden on society. However, the association between quintiles of area-based SES and incident hip fractures has not been examined in Australia. Using a comprehensive register of hip fractures for the entire Barwon Statistical Division (BSD), we assessed the association between area-based SES and incident hip fractures over a two-year period in residents aged ≥ 50years. METHODS: Incident hip fractures were identified using a computerized keyword search of all radiological reports from all the radiological centers serving the BSD. Pathological fractures were excluded. SES was determined by cross-referencing residential addresses with Australian Bureau of Statistics census data and categorized in quintiles based upon the BSD reference range. Homogeneity of population at risk in each SES quintile was tested using chi square comparison. Hip fractures in each quintile and within each age strata for the entire BSD region were defined as rates per 1000 person-years. RESULTS: During 2006-2007, there were 495 hip fractures (336 female). An inverse pattern of association was observed between SES and hip fracture incidence, with a peak in fracture numbers observed in the second quintile of SES, with differences between SES quintiles observed for both females (p = 0.005) and males (p = 0.007). CONCLUSION: The association between incident hip fractures and quintiles of area-based SES provides evidence that those of greater social disadvantage should be a specific target population for intervention to reduce the burden of hip fracture within Australia.

Lower levels of physical activity in childhood associated with adult depression.

Emerging evidence indicates that early life exposures influence adult health outcomes and there is cause to hypothesise a role for physical activity (PA) in childhood as a protective factor in adult depression. This study aimed to investigate the association between self-reported levels of PA in childhood and self-reported depressive illness. Lifetime depression and levels of physical activity (low/high) in childhood (<15 yr) were ascertained by self-report in 2152 adults (20-97 yr) participating in an ongoing epidemiological study in south-eastern Australia. Data were collected between 2000 and 2006. In this sample, 141 women (18.9%) and 169 men (12.0%) reported ever having a depressive episode. Low PA in childhood was associated with an increased risk of reporting depression in adulthood (OR=1.70, 95%CI=1.32-2.17, p<0.001). Adjustment for age, gender and adult PA attenuated the relationship somewhat (OR=1.35, 95%CI=1.01-1.78, p=0.04), however further adjustment for SES or country of birth did not affect this relationship. In this community-based study, lower levels of self-reported PA in childhood were associated with a 35% increase in odds for self-reported depression in adulthood. These results are consistent with the hypothesis that lower levels of PA in childhood may be a risk factor for adult depression.

Patterns of treatment in Australian men following fracture.

UNLABELLED: This study aimed to describe treatment initiation rates for men who had recently sustained a fracture. Most (75.9%) men potentially eligible for subsidised treatment at the time of fracture remained untreated even after a subsequent fracture. INTRODUCTION: This study aimed to describe treatment initiation rates for men who had recently sustained a fracture. METHODS: The study was conducted as part of the Geelong Osteoporosis Study in south-eastern Australia. Men in the study area who had sustained an incident fracture in the period July 2006 to December 2007 were identified from hospital radiology reports. A self-report questionnaire was sent to eligible participants approximately 12 months after fracture. Respondents were asked for details of medications prescribed for 'osteoporosis/fracture/low bone mass' before and after fracture, and where applicable, reasons for cessation of treatment. We analysed the results for 109 men aged 50 years and older who had sustained fracture in the study period. RESULTS: Most (75.9%) men potentially eligible for subsidised treatment at the time of fracture remained untreated. Of the 87 men who were untreated, nine had osteoporosis at the hip and/or spine and 29 (26.6%) reported having sustained a low trauma prior fracture. CONCLUSIONS: Our findings are consistent with previously published data showing low rates of treatment initiation in men eligible for osteoporosis treatment. There appear to be barriers involving participants' and medical practitioners' knowledge, beliefs and attitudes regarding osteoporosis and treatment, as well as in the doctor-patient partnership in osteoporosis management. Establishment of clinical pathways for fracture management beyond orthopaedic care may be one of a range of appropriate responses.

Bone mineral density reference ranges for Australian men: Geelong Osteoporosis Study.

SUMMARY: A large population-based random sample of Australian white men was used to provide normative bone mineral density (BMD) data at multiple anatomical sites. The femoral neck BMD data are very similar to those obtained in USA non-Hispanic white males participating in the National Health and Nutrition Examination Survey III (NHANES III). The reference ranges will be suitable for similar populations. INTRODUCTION: To provide normative BMD data for Australian men derived from a large population-based random sample. METHODS: An age-stratified random sample of men was recruited from the Australian electoral rolls (n = 1,467 aged 20-97 years). BMD was quantified at multiple sites using Lunar densitometers. RESULTS: Age-related differences in BMD were best predicted by linear relationships at the spine and hip and by quadratic functions at the whole body and forearm. At the spine, a small age-related increase in mean BMD was observed. Although in the subset with no spinal abnormalities, there was a decrease of 0.003 g/cm(2) per year from age 20. At the hip sites, mean BMD decreased at 0.001-0.006 g/cm(2) per year from age 20. At the forearm and whole body, BMD peaked at 41-47 years. Apart from a small difference in men greater than or equal to 80 years, the Australian femoral neck BMD data are not different to those obtained in USA non-Hispanic white males participating in NHANES III and were generally similar to those of large studies from Canada (CaMos) and Spain. CONCLUSIONS: These data supply BMD reference ranges at multiple anatomical sites that will be applicable to white Australian men and similar populations such as USA non-Hispanic white men.

Morphometric vertebral fractures of the lower thoracic and lumbar spine, physical function and quality of life in men.

UNLABELLED: The epidemiology and sequelae of morphometric vertebral fracture (MVF) are poorly documented. We found that MVFs of the lower thoracic and lumbar spine were associated with poor quality of life and impaired physical function in men. We recommend that morphometric X-ray absorptiometry be included in routine requests for bone densitometry. INTRODUCTION: Vertebral fractures are sentinel events for osteoporosis. We aimed to compare quality of life and physical function in men with and without MVF. METHODS: Using morphometric X-ray absorptiometry (T10-L4), MVFs were identified in a random sample of men aged 20-93 years. Moderate and severe wedge, biconcave or compression deformities (>25% reduction in any vertebral height) were classified as MVFs. RESULTS: Of 1,147 men, MVFs were identified in 64. No MVFs were detected for men in their twenties. Prevalence was 1.5% for 30-39 years, 1.4% 40-49 years, 3.2% 50-59 years, 4.7% 60-69 years, 10.0% 70-79 years and 14.6% 80+ years. Among 555 men aged 60+ years, those with MVFs were twice as likely to have quality of life scores in the lowest tertile (age-adjusted OR = 2.35, 95%CI 1.24-4.45). MVFs were associated with lower mean age-adjusted physical activity scores [11.3 (95%CI 9.0-13.8) vs 14.0 (13.2-14.9), P = 0.04] and longer mean age-adjusted 'Up-&-Go' times [9.5 (8.9, 10.1) vs 8.9 (8.8, 9.1) s, P = 0.06]. CONCLUSION: Despite most men being unaware of their condition, MVFs were associated with poor quality of life and impaired physical function. We recommend that morphometric X-ray absorptiometry be included in routine requests for bone densitometry because detection of MVFs has important implications for osteoporosis management in men.