Previous fracture and subsequent fracture risk: a meta-analysis to update FRAX.

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

Update of the fracture risk prediction tool FRAX: a systematic review of potential cohorts and analysis plan.

We describe the collection of cohorts together with the analysis plan for an update of the fracture risk prediction tool FRAX with respect to current and novel risk factors. The resource comprises 2,138,428 participants with a follow-up of approximately 20 million person-years and 116,117 documented incident major osteoporotic fractures. INTRODUCTION: The availability of the fracture risk assessment tool FRAX® has substantially enhanced the targeting of treatment to those at high risk of fracture with FRAX now incorporated into more than 100 clinical osteoporosis guidelines worldwide. The aim of this study is to determine whether the current algorithms can be further optimised with respect to current and novel risk factors. METHODS: A computerised literature search was performed in PubMed from inception until May 17, 2019, to identify eligible cohorts for updating the FRAX coefficients. Additionally, we searched the abstracts of conference proceedings of the American Society for Bone and Mineral Research, European Calcified Tissue Society and World Congress of Osteoporosis. Prospective cohort studies with data on baseline clinical risk factors and incident fractures were eligible. RESULTS: Of the 836 records retrieved, 53 were selected for full-text assessment after screening on title and abstract. Twelve cohorts were deemed eligible and of these, 4 novel cohorts were identified. These cohorts, together with 60 previously identified cohorts, will provide the resource for constructing an updated version of FRAX comprising 2,138,428 participants with a follow-up of approximately 20 million person-years and 116,117 documented incident major osteoporotic fractures. For each known and candidate risk factor, multivariate hazard functions for hip fracture, major osteoporotic fracture and death will be tested using extended Poisson regression. Sex- and/or ethnicity-specific differences in the weights of the risk factors will be investigated. After meta-analyses of the cohort-specific beta coefficients for each risk factor, models comprising 10-year probability of hip and major osteoporotic fracture, with or without femoral neck bone mineral density, will be computed. CONCLUSIONS: These assembled cohorts and described models will provide the framework for an updated FRAX tool enabling enhanced assessment of fracture risk (PROSPERO (CRD42021227266)).

Effect of genotype and sex on carcase composition, physicochemical properties, texture and microstructure of meat from geese after four reproductive seasons.

1. The objective of this study was to compare carcase weight and composition and meat quality traits of Landes, Slovak White and Kuban geese after four reproductive seasons. A total of 42 goose carcases (seven males and seven females from each breed) were assessed.2. After four reproductive seasons, the breeds differed in eviscerated carcase weight. Slovak White geese showed more breast muscle with a cooking loss, whereas Kuban geese had a higher percentage of neck and carcase discards compared to the other breeds. The breeds differed in the chemical composition of breast and leg muscles, except for collagen in breast muscles and protein in leg muscles.3. Regardless of breed, males had heavier carcase weight and higher breast muscle, leg muscle, neck and wings and lower percentages of skin with subcutaneous fat and abdominal fat relative to body weight compared to females. Sex had a significant effect on the fat and salt content, meat lightness, most textural characteristics and endomysium thickness of breast muscle. The same differences in leg muscles for chemical composition (except for protein percentage) and lightness were recorded.4. Breed x sex interactions were significant for the proportion of leg muscle, chemical composition of breast and leg muscles (except for leg protein content), muscle fibre cross-sectional area and fibre perimeter of pectoralis major muscle.5. The results showed that the carcases and meat of the goose breeds after four reproductive seasons were suitable for consumers and meat processors, due to favourable composition, high nutritive value and good technological properties.

Repurposing a fracture risk calculator (FRAX) as a screening tool for women at risk for sarcopenia.

Osteoporosis and sarcopenia share risk profiles, so we tested a fracture risk assessment tool (FRAX) as a screening tool for sarcopenia. FRAX probabilities without bone mineral density predicted sarcopenia with high sensitivity and reasonable specificity. There is potential to use this FRAX as a screening tool for sarcopenia. PURPOSE: There is a need for simple screening tools for sarcopenia. As osteoporosis and sarcopenia share risk profiles, we tested the performance of a fracture risk assessment tool for discriminating individuals at risk for sarcopenia. METHODS: In this longitudinal study, FRAX (Australia) probabilities were calculated for 354 women (ages 40-90 years) in the Geelong Osteoporosis Study. Sarcopenia was assessed a decade later using DXA-derived low appendicular lean mass (Lunar; ALM/height2 < 5.5 kg/m2) and low handgrip strength (Jamar; HGS < 16 kg), according to EWGSOP2. We determined FRAX probabilities (%) for hip fracture (HF-FRAX) and major osteoporotic fracture (MOF-FRAX), with and without BMD. Area under the receiver operator characteristic (AUROC) curves quantified the performance of FRAX for predicting sarcopenia. RESULTS: Baseline median (IQR) values for HF-FRAX without BMD were 0.4 (0.1-1.3) and for MOF-FRAX without BMD, 2.4 (1.2-5.2); comparable figures for HF-FRAX with BMD were 0.2 (0.0-0.7) and for MOF-FRAX with BMD, 2.1 (1.1-4.4). At follow-up, sarcopenia was identified for 11 (3.1%) women. When FRAX was calculated without BMD, the AUROC was 0.90 for HF-FRAX and 0.88 for MOF-FRAX. Optimal thresholds were 0.9 for HF-FRAX (sensitivity 90.9%, specificity 62.4%) and 5.3 for MOF-FRAX (sensitivity 81.8%, specificity 71.7%). Calculating FRAX with BMD did not improve the predictive performance of FRAX for sarcopenia. CONCLUSION: Here we provide preliminary evidence to suggest that FRAX probabilities without BMD might predict sarcopenia with high sensitivity and reasonable specificity. Given that FRAX clinical risk factors are identified without equipment, there is potential to use this or a modified version of the FRAX tool to screen for individuals at risk of sarcopenia.

Bone mineral density in diabetes and impaired fasting glucose.

We report that compared with normoglycaemia, post-menopausal women (non-obese and obese) with diabetes had higher lumbar spine bone mineral density (LSBMD). Femoral neck bone mineral density (FNBMD) was higher in obese post-menopausal women with diabetes. Only non-obese post-menopausal women with impaired fasting glucose (IFG) had a higher LSBMD than normoglycaemia. No other associations with IFG were observed. INTRODUCTION: Individuals with diabetes have a higher or normal bone mineral density (BMD) compared with those without diabetes. However, paradoxically, they also have a higher fracture risk. It is not clear whether those with IFG also have altered BMD. This study aimed to determine whether individuals with IFG have elevated or normal BMD. METHODS: Women (n = 858) and men (n = 970) (aged 20-80 years) from the Geelong Osteoporosis Study were included. IFG was defined as fasting plasma glucose (FPG) 5.5-6.9 mmol/L and diabetes as FPG ≥ 7.0 mmol/L, use of antihyperglycaemic medication and/or self-report. Using multivariable linear regression, the relationships between glycaemia and BMD at the femoral neck and lumbar spine were examined, and adjusted for age, body mass index (BMI), and other variables. In women, two interaction terms were identified: menopause × glycaemia and BMI × glycaemia, and thus, the analyses were stratified by menopause and obesity status (BMI cut point ≥ 30 kg/m2). RESULTS: There were no associations between glycaemic status and BMD for pre-menopausal women. For non-obese post-menopausal women, there was no association between FNBMD and glycaemic status, but women with IFG or diabetes had higher LSBMD than those with normoglycaemia (7.1% and 9.7%, respectively, both p < 0.01). Obese post-menopausal women with diabetes had a higher FNBMD (8.8%, p = 0.008) and LSBMD (12.2%, p < 0.001), but those with IFG were not different from the normoglycaemia group. There were no associations detected between glycaemic status and BMD in men. CONCLUSIONS: In this study, we report that compared with normoglycaemia, post-menopausal women (non-obese and obese) with diabetes had higher LSBMD. FNBMD was higher in obese post-menopausal women with diabetes. Only non-obese post-menopausal women with IFG had a higher LSBMD than normoglycaemia. No other associations with IFG were observed.

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.

Carcass composition and selected meat quality traits of Pekin ducks from genetic resources flocks.

The aim of the study was to compare P33 (Polish Pekin), P8 (Danish Pekin), and P9 ducks (French Pekin) for body weight, dressing percentage, carcass composition, and selected meat quality traits. A total of 180 ducks, 30 males and 30 females of each strain, were kept indoors on deep litter and fed complete commercial diets ad libitum. At the end of 8 wk, the ducks were weighed and 7 males and 7 females of each strain (42 birds in total) were slaughtered and dissected. The pH and electrical conductivity of breast and leg muscles were determined 24 h postmortem. After dissection, samples of breast and leg muscles were collected to determine of selected meat quality characteristics. At the age of 8 wk, P8 ducks had significantly higher body weight and carcass weight compared to P9 and P33 birds. The carcasses of P8 ducks contained significantly more breast muscles compared to the carcasses of P9 birds. The proportion of abdominal fat was higher in P8 and P9 ducks than in P33 ducks. Regardless of the genetic origin, males had a significantly lower percentage of breast muscles and a higher proportion of neck in the carcass compared to females. P33, P8, and P9 ducks exhibited significant differences in the sodium and magnesium content of breast muscles and in the sodium, potassium, phosphorus, and magnesium content of leg muscles. Male breast muscles contained more sodium, and their leg muscles had a lower potassium, phosphorus, magnesium, and iron content compared to females. The breast and leg muscles of P9 ducks exhibited lower electrical conductivity (EC24) compared to P8 and P33 ducks, while the breast muscles of P9 ducks had a significantly higher cooking loss. The strains of ducks under study differed in lightness (L*) and redness (a*), and in hardness, chewiness and gumminess of pectoralis major muscle. Females showed higher hardness and chewiness of breast muscles compared to males.

Age-related changes in the carcass composition and meat quality of fallow deer (DAMA DAMA L.).

The present study investigated the possible differences in carcass composition as well as texture, structure and percentage of different muscle types of the most valuable muscles (BF - biceps femoris, SM - semimembranosus, and L - longissimus) from fallow deer (Dama dama L.) bucks shot in the forest farm in north-western Poland at four different ages: 18, 30, 42 and 54 months. It was found that carcasses of young fallow deer (18-30 months), compared to older animals, were characterised by a higher dressing proportion, a higher percentage of the most valuable commercial cuts (the saddle, haunch and shoulder), high meat yield with the lowest percentage of bones and a lower percentage of skin and head. Their muscles, compared with older animals, were characterised by a lower percentage of red fibres, lower muscle fibre area, thinner perimysium and endomysium, lower amount of intramuscular fat and as a consequence lower hardness, springiness, cohesiveness, as well as a higher pH and lower thermal drip.

Prediction of major osteoporotic and hip fractures in Australian men using FRAX scores adjusted with trabecular bone score.

There was no significant difference between the areas under receiver operating characteristics (AUROCs) and diagnostic indexes (sensitivity, specificity, positive predictive value, negative predictive value) for either major osteoporotic or hip fracture FRAX scores when comparing the unadjusted and trabecular bone score (TBS)-adjusted scores. INTRODUCTION: FRAX 10-year probability of fracture can be calculated with adjustment for the TBS. Studies have shown that TBS can improve FRAX assessments in some populations. This study aimed to determine if TBS-adjusted FRAX score is better than the unadjusted score for predicting major osteoporotic fracture (MOF) and hip fracture in Australian men. METHODS: This study involved 591 men aged 40-90 years, enrolled in the Geelong Osteoporosis Study. Incident MOF (n = 50) and hip fractures (n = 14) were ascertained using radiological reports. Median follow-up time was 9.5 years (IQR7.5-11.4). Diagnostic indexes were calculated using cut points of ≥20% for MOF and ≥3% for the hip. AUROC curves were also determined for adjusted and unadjusted scores as continuous variables. RESULTS: Sensitivity was higher in the TBS-adjusted scores (MOF 4%, hip 78.6%) than the unadjusted scores (MOF 2%, hip 57.1%), with a decrease in specificity (MOF 98.9 vs 99.3%; hip 79.9 vs 83.9%). When considering TBS-adjusted and unadjusted FRAX as continuous scores, AUROCs were 0.738 and 0.740, respectively, for MOF and 0.849 and 0.848 for the hip. CONCLUSIONS: Prediction of fractures by MOF or hip FRAX was not substantially improved by TBS adjustment. There was no difference in AUROCs or diagnostic indexes for cut-off points of ≥20 for MOF and ≥3% for hip FRAX.

Lower limb fracture presentations at a regional hospital.

We found that lower limb fractures, which were largely the result of minimal trauma, had high levels of hospitalisation, length of stay and surgery. It is therefore important to prevent fractures at all sites to avoid the associated morbidity and mortality. PURPOSE: Hip fractures are a major cause of morbidity and mortality, particularly in older women. In comparison, less is known about the epidemiology and burden of other lower limb fractures. The study aimed to investigate the epidemiology and burden of these fractures. METHODS: Incident fractures of the hip, femur, tibia/fibula, ankle and foot in women (≥ 20 years) managed through the University Hospital Geelong, Australia, were ascertained from 1 Jan. 2014 to 31 Dec. 2014 from radiology reports. Age, cause of fracture, post-fracture hospitalisation, surgery, length of stay and discharge location were ascertained from medical records. RESULTS: We identified 585 fractures of the lower limb (209 hip, 42 femur, 41 tibia/fibula, 162 ankle, 131 foot). Most fractures were sustained by women aged ≥ 50 years. Fractures were largely a result of minimal trauma. Most women with hip or femur fractures were hospitalised; fewer were hospitalised for fractures at other sites. Surgery for fracture followed the same pattern as hospitalisations. Length of stay was the highest for hip and femur fractures and the lowest for foot fractures. Women with hip or femur fractures were discharged to rehabilitation more often than home. Fractures at other sites were most commonly discharged home. CONCLUSIONS: Fractures of the lower limb occurred frequently in older women. Hospitalisation and subsequent surgery were common in cases of hip and femur fractures. It is important for prevention strategies to target fractures at a range of skeletal sites to reduce costs, hospitalisations, loss of independence and reduced quality of life.

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.

Physical health comorbidities in women with personality disorder: Data from the Geelong Osteoporosis Study.

BACKGROUND: Associations between common psychiatric disorders, psychotic disorders and physical health comorbidities are frequently investigated. The complex relationship between personality disorders (PDs) and physical health is less understood, and findings to date are varied. This study aims to investigate associations between PDs with a number of prevalent physical health conditions. METHODS: This study examined data collected from women (n=765;≥ 25 years) participating in a population-based study located in south-eastern Australia. Lifetime history of psychiatric disorders was assessed using the semi-structured clinical interviews (SCID-I/NP and SCID-II). The presence of physical health conditions (lifetime) were identified via a combination of self-report, medical records, medication use and clinical data. Socioeconomic status, and information regarding medication use, lifestyle behaviors, and sociodemographic information was collected via questionnaires. Logistic regression models were used to investigate associations. RESULTS: After adjustment for sociodemographic variables (age, socioeconomic status) and health-related factors (body mass index, physical activity, smoking, psychotropic medication use), PDs were consistently associated with a range of physical health conditions. Novel associations were observed between Cluster A PDs and gastro-oesophageal reflux disease (GORD); Cluster B PDs with syncope and seizures, as well as arthritis; and Cluster C PDs with GORD and recurrent headaches. CONCLUSIONS: PDs were associated with physical comorbidity. The current data contribute to a growing evidence base demonstrating associations between PDs and a number of physical health conditions independent of psychiatric comorbidity, sociodemographic and lifestyle factors. Longitudinal studies are now required to investigate causal pathways, as are studies determining pathological mechanisms.

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.

The social gradient of fractures at any skeletal site in men and women: data from the Geelong Osteoporosis Study Fracture Grid.

UNLABELLED: Age-specific and age-standardized associations between socioeconomic status (SES) and fractures in adults showed a social gradient of fracture, irrespective of fracture site. Compared to the highest SES, males in the lowest SES group had a sixfold increased odds for any fracture, whilst females had a twofold increased odds. INTRODUCTION: The effective identification of predisposing risk factors for fracture requires understanding any association with SES. These investigations should consider both sexes, span the adult age range and include any fractures. We investigated age- and sex-specific and age-standardized associations between SES and fractures at any skeletal site in Australians aged ≥ 50 years. METHODS: Incident fractures that occurred 2006-2007 for adults aged ≥ 50 years were identified from radiological reports extracted for the Barwon Statistical Division, in south-eastern Australia. SES was determined by cross-referencing residential addresses with Australian Bureau of Statistics census data and then categorized in quintiles. We compared frequencies of observed vs. expected fractures for SES quintiles using χ (2) comparison, calculated age-specific fracture incidence across SES and compared age-standardized fracture rates in SES quintile 1 to quintile 5. RESULTS: We identified 3943 incident fractures (69.4 % female); 47.4 % had occurred at major osteoporotic fracture (MOF) sites (hip, humerus, spine and forearm/wrist). Differences existed in observed vs. expected fractures across SES quintiles (p ≤ 0.001, sexes combined); all fractures showed an inverse association with SES (p ≤ 0.001, sexes combined). Compared to the highest SES quintile, individuals from the lowest SES quintile had between two to six times greater standardized fracture rates. CONCLUSIONS: Disadvantaged men and women have an increased fracture incidence compared to their less disadvantaged counterparts. The large differences in fracture rates between SES groups warrant further research into designing appropriate, targeted interventions for those demographics at most risk.

Is there an interaction between socioeconomic status and FRAX 10-year fracture probability determined with and without bone density measures? Data from the Geelong Osteoporosis Study of female cohort.

FRAX(©) evaluates 10-year fracture probabilities and can be calculated with and without bone mineral density (BMD). Low socioeconomic status (SES) may affect BMD, and is associated with increased fracture risk. Clinical risk factors differ by SES; however, it is unknown whether aninteraction exists between SES and FRAX determined with and without the BMD. From the Geelong Osteoporosis Study, we drew 819 females aged ≥50 years. Clinical data were collected during 1993-1997. SES was determined by cross-referencing residential addresses with Australian Bureau of Statistics census data and categorized in quintiles. BMD was measured by dual energy X-ray absorptiometry at the same time as other clinical data were collected. Ten-year fracture probabilities were calculated using FRAX (Australia). Using multivariable regression analyses, we examined whether interactions existed between SES and 10-year probability for hip and any major osteoporotic fracture (MOF) defined by use of FRAX with and without BMD. We observed a trend for a SES * FRAX(no-BMD) interaction term for 10-year hip fracture probability (p = 0.09); however, not for MOF (p = 0.42). In women without prior fracture (n = 518), we observed a significant SES * FRAX(no-BMD) interaction term for hip fracture (p = 0.03) and MOF (p = 0.04). SES does not appear to have an interaction with 10-year fracture probabilities determined by FRAX with and without BMD in women with previous fracture; however, it does appear to exist for those without previous fracture.

Prior fracture as a risk factor for future fracture in an Australian cohort.

SUMMARY: This study investigated the influence of prior fracture on the risk of subsequent fracture. There was a higher risk of subsequent fracture in both young and older adult age groups when Australian males or females had already sustained a prior fracture. Fracture prevention is important throughout life for both sexes. INTRODUCTION: The purpose of this study was to determine the impact of prior fracture on the risk of subsequent fracture across the adult age range in Australian males and females. METHODS: All-cause fractures were grouped into age categories for males and females enrolled in the Geelong Osteoporosis Study (Australia) using retrospective self-report data and prospective radiology-confirmed data. For all age categories, the relative risk (RR and 95% confidence interval (CI)) of subsequent fracture in a later age category was compared between those with prior fracture and those without. RESULTS: For both sexes, childhood fracture increased the risk of subsequent fracture in adolescence (males: RR 21.7; 95% CI 16.0, 27.4; females: RR 8.1; 3.5, 12.8). Males with adolescent fracture had increased risk of subsequent fracture in early adulthood (RR 11.5; 5.7, 17.3) and mid-adulthood (RR 13.0; 6.3, 19.7). Additionally, males with young adulthood or mid-adulthood fracture had increased risk of subsequent fracture in the following age group (RR 11.2; 4.4, 17.9, and RR 6.2; 0.8, 11.7, respectively). Mid-adult fractures increased the risk of subsequent fracture in older adulthood (RR 6.2; 0.8, 11.7). Females with childhood or adolescent fracture had an increased risk of fracture in young adulthood (RR 4.3; 0.7, 7.9, and RR 10.5; 4.4, 16.6), and prior fracture in older adult life increased the risk of subsequent fracture in old age (RR 14.9; 6.4. 23.3). CONCLUSIONS: Fracture prevention strategies may be more effective if attention is directed towards individuals with prior fracture at any age as they have a higher likelihood of sustaining a subsequent fracture later in life.

The association between critical illness and changes in bone turnover in adults: a systematic review.

SUMMARY: Critical illness may lead to altered bone turnover and associated adverse health outcomes. This systematic review found moderate evidence for a positive association between critical illness and increased bone turnover. Prospective cohort studies that identify the extent and risk factors for critical illness related bone loss are required. INTRODUCTION: Intensive care patients face health issues that extend beyond their critical illness and result in significant morbidity and mortality. Critical illness may result in altered bone turnover due to associated immobilisation, inflammation, exposure to medications that effect bone and calcium metabolism, and endocrine dysfunction. The aim of this study was to synthesise the existing evidence for altered bone turnover in adults admitted to intensive care. METHODS: A literature search using MEDLINE and EMBASE was performed from 1965 to March 2013. Reviewed studies investigated the relationship between critical illness and evidence of altered bone turnover (bone turnover markers, bone mineral density, or fracture). Studies were rated upon their methodological quality, and a best-evidence synthesis was used to summarise the results. RESULTS: Four cohort and seven case-control studies were identified for inclusion, of which five studies were rated as being of higher methodological quality. Ten of the studies measured bone turnover markers, and one study fracture rate. Findings were consistent across studies, and best-evidence analysis resulted in a conclusion that moderate evidence exists for an association between critical illness requiring admission to intensive care and altered bone turnover. CONCLUSION: A positive association between critical illness requiring intensive care admission and bone turnover exists, although data are limited, and the risk factors and the nature of the relationship are not yet understood. Prospective cohort studies that identify risk factors and extent of critical illness related bone turnover changes are required.

Glycaemic control and long-term outcomes following transition from modified intensive insulin therapy to conventional glycaemic control.

This retrospective observational cohort study compared glycaemic control and long-term outcomes following transition from a modified intensive insulin therapy (mIIT) regimen to conventional glycaemic control (CGC) in adult patients admitted to a tertiary adult general intensive care unit, during two 24-month periods, before and after the publication of the Normoglycemia in Intensive Care Evaluation and Surviving Using Glucose Algorithm Regulation (NICE-SUGAR) trial. The before NICE-SUGAR cohort received mIIT (target glycaemic ranges 4.4 to 7.0 mmol/l), while the after NICE-SUGAR cohort received CGC (target glycaemic range 7.1 to 9.0 mmol/l). A total of 5202 patients were included in the study. With transition from mIIT to CGC, the mean time-weighted glucose increased from 6.94 mmol/l to 8.2 mmol/l (P <0.0001). A similar increase was observed in other glycaemic indices (mean, highest and lowest glucose values, P <0.0001 for all). The adjusted 90-day odds ratio for mortality decreased by 47% with transition from mIIT to CGC (odds ratio 1.47 (95% confidence interval, 1.22 to 1.78) (P <0.0001). The rate of severe and moderate hypoglycaemia also decreased from 1.2 to 0.4% (P=0.004) and from 23.3 to 5.9% (P <0.0001), respectively. mIIT was associated with an increased risk of moderate and severe hypoglycaemia compared to CGC (odds ratio 3.1 (1.51 to 6.39) (P=0.002), 6.29 (5.1 to 7.75) (P <0.0001)). Changes in recommended glycaemic control were translated into practice, with increased glycaemic indices and decreased rates of severe and moderate hypoglycaemia after the introduction of CGC. The associated decrease in 90-day mortality suggests mIIT was not superior to CGC, despite a lower hypoglycaemia rate than in previous IIT trials. Our findings support the continued use of CGC.

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.

Examining the impact of reimbursement on referral to bone density testing for older adults: 8 years of data from the Barwon Statistical Division, Australia.

UNLABELLED: In 2007, Medicare Australia revised rei:mbursement guidelines for dual energy X-ray absorptiometry (DXA) for Australians aged ≥70 years; we examined whether these changes increased DXA referrals in older adults. Proportions of DXA referrals doubled for men and tripled for women from 2003 to 2010; however, rates of utilization remained low. INTRODUCTION: On April 1, 2007 Medicare Australia revised reimbursement guidelines for DXA for Australians aged ≥70 year; changes that were intended to increase the proportion of older adults being tested. We examined whether changes to reimbursement increased DXA referrals in older adults, and whether any sex differences in referrals were observed in the Barwon Statistical Division. METHODS: Proportions of DXA referrals 2003-2010 based on the population at risk ascertained from Australian Census data and annual referral rates and rate ratios stratified by sex, year of DXA, and 5-year age groups. Persons aged ≥70 years referred to the major public health service provider for DXA clinical purposes (n = 6,096; 21 % men). RESULTS: DXA referrals. Proportions of DXA referrals for men doubled from 0.8 % (2003) to 1.8 % (2010) and tripled from 2.0 to 6.3 % for women (all p < 0.001). For 2003-2006, referral ratios of men/women ranged between 1:1.9 and 1:3.0 and for 2007-2010 were 1:2.3 to 1:3.4. Referral ratios <2007:≥2007 were 1:1.7 for men aged 70-79 years (p < 0.001), 1:1.2 for men aged 80-84 years (p = 0.06), and 1:1.3 for men 85+ years (p = 0.16). For women, the ratios <2007:≥2007 were 1:2.1 (70-79 years), 1.1.5 (80-84 years), and 1:1.4 (85+ years) (all p < 0.001). CONCLUSIONS: DXA referral ratios were 1:1.6 (men) and 1:1.8 (women) for 2007-2010 vs. 2003-2006; proportions of referrals doubled for men and tripled for women from 2003 to 2010. Overall, rates of DXA utilization remained low. Policy changes may have had minimal influence on referral; thus, ongoing evaluation over time is warranted.