Australian Institute for Musculoskeletal Science

Melbourne, Australia

Australian Institute for Musculoskeletal Science

Melbourne, Australia
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Buenzli P.R.,Monash University | Buenzli P.R.,University of Western Australia | Thomas C.D.L.,University of Melbourne | Clement J.G.,University of Melbourne | And 2 more authors.
International Journal for Numerical Methods in Biomedical Engineering | Year: 2013

Age-related bone loss and postmenopausal osteoporosis are due to a dysregulation of bone remodelling in which less bone is reformed than resorbed. This dysregulation of bone remodelling does not occur with equal strength in all bone regions. Loss of bone is more pronounced near the endocortical surface. This leads to thinning of the cortical wall proceeding from the endosteum, a process sometimes called 'trabecularisation'. In this paper, we investigate the influence of the nonuniform distribution of bone surface within bone tissue for osteoporotic bone losses. We use a spatio-temporal computational model of bone remodelling in which microstructural changes of bone tissue are represented by a phenomenological relationship between bone specific surface and bone porosity. The simulation of an osteoporotic condition by our model shows that the evolution of bone porosity within a bone cross section is significantly influenced by the nonuniform availability of bone surface. Greater bone loss occurs near the endocortical wall, leading to cortical wall thinning and to an expansion of the medullary cavity similar to cross-sectional observations from human femur midshafts. Our model suggests that the rate of cortical wall thinning is fast/slow in the presence/absence of an adjacent trabecular or trabecularised bone compartment. © 2013 John Wiley & Sons, Ltd.


Brennan S.L.,Deakin University | Brennan S.L.,University of Melbourne | Brennan S.L.,Australian Institute for Musculoskeletal science | Yan L.,University of Manitoba | And 5 more authors.
Osteoporosis International | Year: 2014

Summary: We investigated sex- and age-specific associations between income and fractures at the hip, humerus, spine, and forearm in adults aged ≥50 years. Compared to men with the highest income, men with the lowest income had an increased fracture risk at all skeletal sites. These associations were attenuated in women.Introduction: Associations between income and hip fractures are contested, even less is known about other fracture sites. We investigated sex- and age-specific associations between income and major osteoporotic fractures (MOF) at the hip, humerus, spine, and forearm.Methods: Incident fractures were identified from administrative health data for adults aged ≥50 years in Manitoba, Canada, 2000–2007. Mean neighborhood (postal code area) annual household incomes were extracted from 2006 census files and categorized into quintiles. We calculated age-adjusted and age-specific sex-stratified fracture incidence across income quintiles. We estimated relative risks (RR) and 95 % CI for income quintile 1 (Q1, lowest income) vs. income quintile 5 (Q5) and tested the linear trend across quintiles.Results: We identified 15,094 incident fractures (4736 hip, 3012 humerus, 1979 spine, and 5367 forearm) in 2718 men and 6786 women. For males, the RR of fracture for the lowest vs. highest income quintile was 1.63 (95 % CI 1.42–1.87) and the negative trend was statistically significant (p < 0.0001); individual skeletal sites showed similar associations. For females, the RR of fracture for the lowest vs. highest income quintile was 1.14 (95 % CI 1.01–1.28), with a statistically significant negative trend (p = 0.0291); however, the only skeletal site associated with income in women was the forearm (Q1 vs. Q5 RR 1.09, 95 % CI 1.01–1.28).Conclusions: Compared to men with the highest income, men with the lowest income had an increased fracture risk at all skeletal sites. These associations were attenuated in women. For men, these effect sizes seem large enough to warrant public health concern. © 2014, International Osteoporosis Foundation and National Osteoporosis Foundation.


Williams L.J.,Deakin University | Williams L.J.,University of Melbourne | Berk M.,Deakin University | Berk M.,University of Melbourne | And 11 more authors.
BMJ Open | Year: 2014

Objectives: High levels of disability, functional impairment and mortality are independently associated with fracture and depression, however the relationship between fracture and depression is uncertain. The aim of this study was to investigate whether fracture is associated with subsequent depressive symptoms in a population-based sample of women. Design: A study of age-matched fracture versus non-fracture cohorts of women. Setting: Barwon Statistical Division, southeastern Australia. Participants: Two samples of women aged ≥35 years were drawn from the Geelong Osteoporosis Study (GOS). The fracture cohort included women with incident fracture identified from radiology reports and the non-fracture cohort were randomly selected from the electoral roll during 1994-1996. Outcome measure: Symptoms of depression for women with and without fracture during the 12-month period 2000-2001 were identified by self-report questionnaire based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria. Results: A total of 296 women with fracture (12 hip, 48 vertebral, 91 wrist/forearm, 17 upper arm, 7 pelvis, 11 rib, 62 lower leg and 48 other fractures) and 590 women without fracture were included. Associations between fracture and depression differed between younger (≤65 years) and older (>65 years) women. Age and weight-adjusted odds ratio for depression following fracture among younger women was 0.62 (0.35 to 1.11, p=0.12) and 3.33 (1.24 to 8.98, p=0.02) for older women. Further adjustment for lifestyle factors did not affect the results. Conclusions: This study demonstrated that differences in mood status exist between older and younger women following fracture and that fracture is associated with increased depression in older women. Assessment of mood status in both the short and long term following fracture in the elderly seems justified, with early detection and treatment likely to result in improved outcomes.


Brennan S.L.,University of Melbourne | Brennan S.L.,Australian Institute for Musculoskeletal science | Brennan S.L.,Deakin University | Leslie W.D.,University of Manitoba | And 5 more authors.
Osteoporosis International | Year: 2014

We investigated the fracture risk assessment tool (FRAX) Canada calibration and discrimination according to income quintile in 51,327 Canadian women, with and without a competing mortality framework. Our data show that, under a competing mortality framework, FRAX provides robust fracture prediction and calibration regardless of socioeconomic status (SES). Introduction: FRAX® predicts 10-year fracture risk. Social factors may independently affect fracture risk. We investigated FRAX calibration and discrimination according to SES. Methods: Women aged ≥50 years with baseline femoral neck bone mineral density (BMD) were identified from the Manitoba Bone Density Program, Canada (n = 51,327), 1996-2011. Mean household income, extracted from 2006 census files, was categorized into quintiles. Ten-year fracture probabilities were calculated using FRAX Canada. Incident non-traumatic fractures were studied in relation to income quintile in adjusted Cox proportional hazards models. We compared observed versus predicted fractures with and without a competing mortality framework. Results: During mean 6.2 ± 3.7 years of follow up, there were 6,392 deaths, 3,723 women with ≥1 major osteoporotic fracture (MOF), and 1,027 with hip fractures. Lower income was associated with higher risk for death, MOF, and hip fracture in adjusted models (all p < 0.005). More women in income quintile 1 (lowest) versus quintile 5 experienced death (19 vs. 8 %), MOF (10 vs. 6 %), or hip fracture (3.0 vs. 1.3 %) (all p ≤ 0.001). Adjustment for competing mortality mitigated the effect of SES on FRAX calibration, and good calibration was observed. FRAX provided good fracture discrimination for MOF and hip fracture within each income quintile (all p < 0.001). Area under the curve was slightly lower for income quintiles 1 versus 5 for FRAX with BMD to predict MOF (0.68, 95 % CI 0.66-0.70 vs. 0.71, 95 % CI 0.69-0.74) and hip fracture (0.79, 95 % CI 0.76-0.81 vs. 0.87, 95 % CI 0.84-0.89). Conclusion: Increased fracture risk in individuals of lower income is offset by increased mortality. Under a competing mortality framework, FRAX provides robust fracture prediction and calibration regardless of SES. © 2013 International Osteoporosis Foundation and National Osteoporosis Foundation.


Brennan S.L.,University of Melbourne | Brennan S.L.,Australian Institute for Musculoskeletal science | Brennan S.L.,Deakin University | Leslie W.D.,St Boniface Hospital | Lix L.M.,University of Manitoba
Osteoporosis International | Year: 2013

We examined the independent contribution of income to low bone mineral density in women aged 50 years and older. A significant dose-response association was observed between low income and low (bone mineral density) BMD, which was not explained by clinical risk factors or osteoporotic treatment in the year prior. Introduction: The association between social disadvantage and osteoporosis is attracting increased attention; however, little is known of the role played by income. We examined associations between income and bone mineral density (BMD) in 51,327 women aged ≥50 years from Manitoba, Canada. Methods: Low BMD was defined as a T-score ≥2.5SD (femoral neck or minimum) measured by dual energy X-ray absorptiometry (DXA) 1996-2001. Mean household income was extracted from Canada Census 2006 public use files and categorized into quintiles. Age, weight and height were recorded at time of DXA. Parental hip fracture was self-reported. Diagnosed comorbidities, including osteoporotic fracture and rheumatoid arthritis, were ascertained from hospital records and physician billing claims. Chronic obstructive pulmonary disease was used as a proxy for smoking and alcohol abuse as a proxy for high alcohol intake. Corticosteroid use was obtained from the comprehensive provincial pharmacy system. Logistic regression was used to assess relationships between income (highest income quintile held as referent) and BMD, accounting for clinical risk factors. Results: Compared to quintile 5, the adjusted odds ratio (OR) for low BMD at femoral neck for quintiles 1 through 4 were, respectively, OR1.41 (95 %CI 1.29-1.55), OR1.32 (95 %CI 1.20-1.45), OR1.19 (95 %CI 1.08-1.30) and OR1.10 (95 %CI 1.00-1.21). Similar associations were observed when further adjustment was made for osteoporotic drug treatment 12 months prior and when low BMD was defined by minimum T-score. Conclusions: Lower income was associated with lower BMD, independent of clinical risk factors. Further work should examine whether lower income increases the likelihood of treatment qualification. © 2013 International Osteoporosis Foundation and National Osteoporosis Foundation.


Leslie W.D.,University of Manitoba | Brennan S.L.,University of Melbourne | Brennan S.L.,Australian Institute for Musculoskeletal science | Brennan S.L.,Deakin University | And 5 more authors.
Archives of Osteoporosis | Year: 2013

We compared the calibration of FRAX tools from Canada, the US (white), UK, Sweden, France, Australia, New Zealand, and China when used to assess fracture risk in 36,730 Canadian women. Our data underscores the importance of applying country-specific FRAX tools that are based upon high-quality national fracture epidemiology. Purpose: A FRAX® model for Canada was constructed for prediction of hip fracture and major osteoporotic fracture (MOF) using national hip fracture and mortality data. We examined the calibration of this model in Canadian women and compared it with seven other FRAX tools. Methods: In women aged ≥50 years with baseline bone mineral density (BMD) measures identified from the Manitoba Bone Density Program, Canada (n = 36,730), 10-year fracture probabilities were calculated with and without BMD using selected country-specific FRAX tools. FRAX risk estimates were compared with observed fractures ≤10 years (506 hip, 2,380 MOF). Ten-year fracture risk was compared with predicted probabilities, and proportions exceeding specific treatment thresholds contrasted. Results: For hip fracture prediction, good calibration was observed for FRAX Canada and most other country-specific FRAX tools, excepting Sweden (risk overestimated) and China (risk underestimated). For MOF prediction, greater between-country differences were seen; FRAX Sweden and FRAX China showed the largest over- and underestimation in this Canadian population. Relative to treatment qualification based upon FRAX Canada, treatment of high-hip fracture probability (≥3 %) was greater by FRAX Sweden (ratio 1.41 without and 1.55 with BMD), and markedly less by FRAX China (ratio 0.09 without and 0.11 with BMD). Greater between-country differences were observed for treat4ment of high MOF (≥20 %); FRAX Sweden again greatly increased (ratio 1.76 without and 1.83 with BMD), and FRAX China severely reduced treatment qualification (ratio 0.00 without and 0.01 with BMD). Conclusions: The use of country-specific FRAX tools, accurately calibrated to the target population, is essential. Relatively small calibration differences can have large effects on high-risk categorization and treatment qualification. © 2013 International Osteoporosis Foundation and National Osteoporosis Foundation.


Martelli S.,Flinders University | Martelli S.,University of Melbourne | Pivonka P.,University of Melbourne | Pivonka P.,Australian Institute for Musculoskeletal Science | And 2 more authors.
Clinical Biomechanics | Year: 2014

Background: Atypical femoral fractures are low-energy fractures initiating in the lateral femoral shaft. We hypothesized that atypical femoral fracture onset is associated with daily femoral strain patterns. We examined femoral shaft strains during daily activities. Methods: We analyzed earlier calculations of femoral strain during walking, sitting and rising from a chair, stair ascent, stair descent, stepping up, and squatting based on anatomically consistent musculoskeletal and finiteelement models from a single donor and motion recordings from a body-matched volunteer. Femoral strains in the femoral shaft were extracted for the different activities and compared. The dependency between femoral strains in the lateral shaft and kinetic parameters was studied using multi-parametric linear regression analysis. Findings: Tensile strain in the lateral femoral shaft varied from 327 με (squatting) to 2004 με (walking). Walking and stair descent imposed tensile loading onthe lateral shaft, whereas the other activities mainly imposed tensile loads on the anterior shaft. The multi-parametric linear regression showed a moderately strong correlation between tensile strains in the lateral shaft and the motion kinetic (joint moments and ground reaction force) in the proximal (R2 = 0.60) and the distal shaft (R2 = 0.46). Interpretation: Bone regions subjected to tensile strains are associated with atypical femoral fractures. Walking is the daily activity that induces the highest tensile strain in the lateral femoral shaft. The kinetics of motion explains 46%-50% of the tensile strain variation in the lateral shaft, whereas the unexplained part is likely to be attributed to the way joint moments are decomposed into muscle forces. © 2014 Elsevier Ltd. All rights reserved.


PubMed | Australian Institute for Musculoskeletal Science and University of Melbourne
Type: Journal Article | Journal: The American journal of clinical nutrition | Year: 2016

Reported associations between protein intake from different sources and type 2 diabetes (T2D) have been inconsistent.We prospectively examined the relations of total, animal, and plant protein intakes with incident T2D.We followed 21,523 participants (women: 61.7%) between 1990 and 2007 from the Melbourne Collaborative Cohort Study who were free of diabetes, cardiovascular disease, cancer, and kidney stones at baseline. We also conducted a meta-analysis that included the results from our cohort and from 10 previous prospective studies.A total of 929 new cases (4.3%) of T2D were documented during a mean of 11.7 y of follow-up. Multivariate-adjusted ORs for incident T2D in the highest compared with lowest quintiles of total and animal protein intakes as percentages of energy were 1.23 (95% CI: 0.96, 1.56; P-trend = 0.029) and 1.29 (95% CI: 0.99, 1.67; P-trend = 0.014), respectively. These associations appeared to be greater in men and in participants with normal baseline plasma glucose, body mass index, or blood pressure. Plant protein intake was inversely associated with incident T2D in women only (OR; 0.60; 95% CI: 0.37, 0.99). In the meta-analysis of 11 prospective cohort studies with 505,624 participants and 37,918 T2D cases (follow-up range: 5-24 y), pooled RRs for the comparison of the highest with lowest categories of total, animal, and plant protein intakes were 1.09 (95% CI: 1.06, 1.13), 1.19 (95% CI: 1.11, 1.28), and 0.95 (95% CI: 0.89, 1.02), respectively. Associations between animal protein intake and T2D were similar across sex, geographic region, length of follow-up, study quality, and method of expressing protein intake. An inverse association between plant protein intake and T2D was observed in women (RR: 0.93; 95% CI: 0.85, 1.00) and in US populations (RR: 0.91; 95% CI: 0.84, 0.97).Higher intakes of total and animal protein were both associated with increased risks of T2D, whereas higher plant protein intake tended to be associated with lower risk of T2D.


PubMed | Australian Institute for Musculoskeletal Science, University of Melbourne, Cancer Epidemiology Center and Diwan Chand Satyapal Aggarwaal Diagnostic Imaging Research Center
Type: Journal Article | Journal: The international journal of cardiovascular imaging | Year: 2016

To determine whether adiposity assessed by dual-energy X-ray absorptiometry (DXA) compared to simple anthropometric assessments, are more predictive of abdominal aortic calcification (AAC), a risk factor for atherosclerosis. A cross-sectional study of 312 participants (60.3% female) aged 70.65.6years was conducted in 2010-2011. AAC was assessed by radiography. Adiposity was estimated for whole body, trunk, android, gynoid and visceral regions using DXA in addition to body mass index (BMI), waist circumference (WC) and waist to hip ratio (WHR). WHR [tertile 1 as reference, OR (95% CI) for tertile 3: 3.62 (1.35-9.72)] and android to gynoid fat ratio [tertile 3: 2.87 (1.03-8.01)] were independent predictors of AAC severity among men. Positive associations with AAC severity were observed for WC [tertile 1 as reference, OR for tertile 3: 2.46 (1.12-5.41)], % trunk fat mass [tertile 2: 3.26 (1.52-7.03)], % android fat mass [tertile 2: 2.42 (1.13-5.18), tertile 3: 2.20 (1.02-4.73)] and visceral fat area [tertile 2: 2.28 (1.06-4.87), tertile 3: 2.32 (1.01-5.34)] among women. Indices of total body composition, BMI and % body fat mass were not associated with AAC severity in either men or women. Simple anthropometric measures, WHR and WC were the best predictors of AAC severity in men and women respectively, although higher android to gynoid fat ratio and central fat, assessed by DXA, were also predictive of higher risks of AAC severity in men and women respectively. Our findings add to existing evidence that relatively inexpensive and easily obtained anthropometric measures can be clinically useful indicators of atherosclerosis risk.


Brennan S.L.,University of Melbourne | Brennan S.L.,Australian Institute for Musculoskeletal science | Brennan S.L.,Deakin University | Leslie W.D.,University of Manitoba | Lix L.M.,University of Manitoba
Osteoporosis International | Year: 2014

We examined whether low income was associated with an increased likelihood of treatment qualification for osteoporotic fracture probability determined by Canada FRAX in women aged ≥50 years. A significant negative linear association was observed between income and treatment qualification when FRAX included bone mineral density (BMD), which may have implications for clinical practice. Introduction: Lower income has been associated with increased fracture risk. We examined whether lower income in women was associated with an increased likelihood of treatment qualification determined by Canada FRAX®. Methods: We calculated 10-year FRAX probabilities in 51,327 Canadian women aged ≥50 years undergoing baseline BMD measured by dual energy x-ray absorptiometry 1996-2001. FRAX probabilities for hip fracture ≥3 % or major osteoporotic fracture (MOF) ≥20 % were used to define treatment qualification. Mean household income from Canada Census 2006 public use files was used to categorize the population into quintiles. Logistic regression analyses were used to model the association between income and treatment qualification. Results: Percentages of women who qualified for treatment based upon high hip fracture probability increased linearly with declining income quintile (all p trend <0.001), but this was partially explained by older age among lower income quintiles (p trend <0.001). Compared to the highest income quintile, women in the lowest income quintile had a greater likelihood of treatment qualification based upon high hip fracture probability determined with BMD (age-adjusted odds ratio [OR], 1.34; 95 % confidence intervals (CI), 1.23-1.47) or high MOF fracture probability determined with BMD (age-adjusted OR, 1.31; 95 % CI, 1.18-1.46). Differences were nonsignificant when FRAX was determined without BMD, implying that BMD differences may be the primary explanatory factor. Conclusions: FRAX determined with BMD identifies a larger proportion of lower income women as qualifying for treatment than higher income women. © 2013 International Osteoporosis Foundation and National Osteoporosis Foundation.

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