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Objectives: To project how many minimal trauma fractures could be averted in Australia by expanding the number and changing the operational characteristics of fracture liaison services (FLS)., Study Design: System dynamics modelling., Setting, Participants: People aged 50 years or more who present to hospitals with minimal trauma fractures, Australia, 2020-31., Main Outcome Measures: Numbers of all minimal trauma fractures and of hip fractures averted by increasing the FLS number (from 29 to 58 or 100), patient screening rate (from 30% to 60%), and capacity for accepting new patients (from 40 to 80 per service per month), and reducing the proportion of eligible patients who do not attend FLS (from 30% to 15%); cost per fracture averted., Results: Our model projected a total of 2 441 320 minimal trauma fractures (258 680 hip fractures; 2 182 640 non-hip fractures) in people aged 50 years or older during 2020-31, including 1 211 646 second or later fractures. Increasing the FLS number to 100 averted a projected 5405 fractures (0.22%; $39 510 per fracture averted); doubling FLS capacity averted a projected 3674 fractures (0.15%; $35 835 per fracture averted). Our model projected that neither doubling the screening rate nor reducing by half the proportion of eligible patients who did not attend FLS alone would reduce the number of fractures. Increasing the FLS number to 100, the screening rate to 60%, and capacity to 80 new patients per service per month would together avert a projected 13 672 fractures (0.56%) at a cost of $42 828 per fracture averted., Conclusion: Our modelling indicates that increasing the number of hospital-based FLS and changing key operational characteristics would achieve only moderate reductions in the number of minimal trauma fractures among people aged 50 years or more, and the cost would be relatively high. Alternatives to specialist-led, hospital-based FLS should be explored., (© 2024 The Authors. Medical Journal of Australia published by John Wiley & Sons Australia, Ltd on behalf of AMPCo Pty Ltd.)

Coordinating healthcare activities between fracture liaison services (FLS) and primary care is challenging. Using a Delphi technique, we developed 34 consensus statements to support improved care coordination across this healthcare transition., Purpose: Evidence supporting an optimal coordination strategy between fracture liaison services (FLS) and primary care is lacking. This study aimed to develop consensus statements to support consistency and benchmarking of clinical practice to improve coordination of care for patients transitioning from FLS to primary care following an osteoporotic fracture., Methods: A Delphi technique was used to develop consensus among a panel of experts, including FLS clinicians (medical and non-medical), general practitioners (GPs), and consumers., Results: Results of a preparatory questionnaire (n = 33) informed the development of 34 statements for review by expert panellists over two Delphi rounds (n = 25 and n = 19, respectively). The majority of participants were from New South Wales (82%), employed as FLS clinicians (78.8%) and working in metropolitan centres (60.6%). Consensus was achieved for 24/34 statements in round one and 8/10 statements in round two. All statements concerning patient education, communication, and the GP-patient relationship achieved consensus. Expert opinions diverged in some areas of clinician roles and responsibilities and long-term monitoring and management recommendations., Conclusion: We found clear consensus among experts in many key areas of FLS integration with primary care. While experts agreed that primary care is the most appropriate setting for long-term osteoporosis care, overall confidence in primary care systems to achieve this was low. The role of (and responsibility for) adherence monitoring in a resource-limited setting remains to be defined., (© 2024. The Author(s).)

Importance: The relationship between self-reported walking limitation, a proxy of muscle function, and fracture risk has not been investigated., Objective: To examine the association between a self-reported walking limitation of 1000 m or less and 5-year risk of fracture., Design, Setting, and Participants: This prospective cohort study compared individuals with various degrees of walking ability limitation at 1000 m (a little limitation and a lot of limitation) and those without limitation (no limitation) accounting for age, falls, prior fractures, and weight. Participants from the ongoing population-based Sax Institute 45 and Up Study were followed from recruitment (2005-2008) for 5 years (2010-2013). Data analysis was conducted from July 2020 to September 2023., Exposure: Self-reported walking limitation., Main Outcomes and Measures: Incident fracture and site-specific fractures (hip, vertebral, and nonhip nonvertebral [NHNV] fractures)., Results: Among the 266 912 participants enrolled in the 45 and Up Study, 238 969 were included, with 126 015 (53%) women (mean [SD] age, 63 [11] years) and 112 954 (47%) men (mean [SD] age, 61 [11] years). Approximately 20% reported a degree of limitation in walking 1000 m or less at baseline (39 324 women [24%]; 23 191 men [21%]). During a mean (SD) follow-up of 4.1 (0.8) years, 7190 women and 4267 men experienced an incident fracture. Compared with participants who reported no walking limitations, a little limitation and a lot of limitation were associated with higher risk of fracture (a little limitation among women: hazard ratio [HR], 1.32; 95% CI, 1.23-1.41; a little limitation among men: HR, 1.46; 95% CI, 1.34-1.60; a lot of limitation among women: HR, 1.60; 95% CI, 1.49-1.71; a lot of limitation among men: HR, 2.03; 95% CI, 1.86-2.22). Approximately 60% of fractures were attributable to walking limitation. The association was significant for hip, vertebral, and NHNV fracture and ranged between a 21% increase to a greater than 219% increase., Conclusions and Relevance: In this cohort study of 238 969 participants, self-reported walking limitations were associated with increased risk of fracture. These findings suggest that walking ability should be sought by clinicians to identify high-risk candidates for further assessment.

To examine an impact of three types of bariatric surgery compared with dietary intervention (DIET), on concurrent changes in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) and appetite hormones over 3 years. Fifty-five adults were studied during phase of weight loss (0-12 months) and during weight stability (12-36 months) post intervention. Measurements of HOMA-IR, fasting and postprandial PYY and GLP1, adiponectin, CRP, RBP4, FGF21 hormones and dual-Xray absorptiometry were performed throughout the study. All surgical groups achieved significant reductions in HOMA-IR with greatest difference between Roux-en-Y gastric bypass and DIET (- 3.7; 95% CI - 5.4, - 2.1; p = 0.001) at 12-36 months. Initial (0-12 months) HOMA-IR values were no different to DIET after adjustment for the lost weight. During 12-36 months, after controlling for treatment procedure and weight, for every twofold increase in postprandial PYY and adiponectin, HOMA-IR decreased by 0.91 (95% CI - 1.71, - 0.11; p = 0.030) and by 0.59 (95% CI - 1.10, - 0.10; p = 0.023) respectively. Initial, non-sustained changes in RBP4 and FGF21 were not associated with HOMA-IR values. While initial rapid weight loss reduces insulin resistance, the enhanced secretions of PYY and adiponectin may contribute to weight-independent improvements in HOMA-IR during weight stability.Clinical trial registration: Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12613000188730., (© 2023. The Author(s).)

Background: Multimorbidity is common among fracture patients. However, its association with osteoporosis investigation and treatment to prevent future fractures is unclear. This limited knowledge impedes optimal patient care. This study investigated the association between multimorbidity and osteoporosis investigation and treatment in persons at high risk following an osteoporotic fracture., Methods and Findings: The Sax Institute's 45 and Up Study is a prospective population-based cohort of 267,153 people in New South Wales, Australia, recruited between 2005 and 2009. This analysis followed up participants until 2017 for a median of 6 years (IQR: 4 to 8). Questionnaire data were linked to hospital admissions (Admitted Patients Data Collection (APDC)), emergency presentations (Emergency Department Data Collection (EDDC)), Pharmaceutical Benefits Scheme (PBS), and Medicare Benefits Schedule (MBS). Data were linked by the Centre for Health Record Linkage and stored in a secured computing environment. Fractures were identified from APDC and EDDC, Charlson Comorbidity Index (CCI) from APDC, Dual-energy X-ray absorptiometry (DXA) investigation from MBS, and osteoporosis treatment from PBS. Out of 25,280 persons with index fracture, 10,540 were classified as high-risk based on 10-year Garvan Fracture Risk (age, sex, weight, prior fracture and falls) threshold ≥20%. The association of CCI with likelihood of investigation and treatment initiation was determined by logistic regression adjusted for education, socioeconomic and lifestyle factors). The high-risk females and males averaged 77 ± 10 and 86 ± 5 years, respectively; >40% had a CCI ≥2. Only 17% of females and 7% of males received a DXA referral, and 22% of females and 14% males received osteoporosis medication following fracture. A higher CCI was associated with a lower probability of being investigated [adjusted OR, females: 0.73 (95% CI, 0.61 to 0.87) and 0.43 (95% CI, 0.30 to 0.62); males: 0.47 (95% CI, 0.33 to 0.68) and 0.52 (0.31 to 0.85) for CCI: 2 to 3, and ≥4 versus 0 to 1, respectively] and of receiving osteoporosis medication [adjusted OR, females: 0.85 (95% CI, 0.74 to 0.98) and 0.78 (95% CI, 0.61 to 0.99); males: 0.75 (95% CI, 0.59 to 0.94) and 0.37 (95% CI, 0.23 to 0.53) for CCI: 2 to 3, and ≥4 versus 0 to 1, respectively]. The cohort is relatively healthy; therefore, the impact of multimorbidity on osteoporosis management may have been underestimated., Conclusions: Multimorbidity contributed significantly to osteoporosis treatment gap. This suggests that fracture risk is either underestimated or underprioritized in the context of multimorbidity and highlights the need for extra vigilance and improved fracture care in this setting., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: WC has given educational talks for Amgen. KEE has received grants from the National Institute of Health. RDB has been a consultant for Bristol Myers Squibb, served on an advisory board for Amgen, received authorship royalties from Wolters Kluwer, received an editorial stipend from Elsevier, received travel support from Amgen, and owns stock in Abbott Labs, Abbvie, Amgen, JangoBio, and Procter & Gamble. JRC has been on a medical advisory board for Amgen and given educational talks for Amgen and Teva. DB, TT, LM, FB, DA and DA have no conflict of interest to declare., (Copyright: © 2023 Bliuc et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The Australian Health Economics Model of Osteoporosis (AusHEMO) has shown good face, internal and cross validities, and can be used to assist healthcare decision-making in Australia., Purpose: This study aimed to document and validate the risk engine of the Australian Health Economics Model of Osteoporosis (AusHEMO)., Methods: AusHEMO is a state-transition microsimulation model. The fracture risks were simulated using fracture incidence rates from the Dubbo Osteoporosis Epidemiology Study. The AusHEMO was validated regarding its face, internal and cross validities. Goodness-of-fit analysis was conducted and Lin's coefficient of agreement and mean absolute difference with 95% limits of agreement were reported., Results: The development of AusHEMO followed general and osteoporosis-specific health economics guidelines. AusHEMO showed good face validity regarding the model's structure, evidence, problem formulation and results. In addition, the model has been proven good internal and cross validities in goodness-of-fit test. Lin's coefficient was 0.99, 1 and 0.94 for validation against the fracture incidence rates, Australian life expectancies and residual lifetime fracture risks, respectively., Conclusions: In summary, the development of the risk engine of AusHEMO followed the best practice for osteoporosis disease modelling and the model has been shown to have good face, internal and cross validities. The AusHEMO can be confidently used to predict long-term fracture-related outcomes and health economic evaluations when costs data are included. Health policy-makers in Australia can use the AusHEMO to select which osteoporosis interventions such as medications and public health interventions represent good value for money., (© 2021. International Osteoporosis Foundation and National Osteoporosis Foundation.)

Context: Muscle strength and performance are associated with fractures. However, the contribution of their rate of decline is unclear., Objective: To assess the independent contribution of the rate of decline in muscle strength and performance to fracture risk., Design, Setting, and Participants: Community-dwelling women (n = 811) and men (n = 440) aged 60 years or older from the prospective Dubbo Osteoporosis Epidemiology Study followed from 2000 to 2018 for incident fracture. Clinical data, appendicular lean mass/height2 (ht)2, bone mineral density, quadricep strength/ht (QS), timed get-up-and-go (TGUG), 5 times repeated sit-to-stand (5xSTS), and gait speed (GS) measured biennially. Rates of decline in muscle parameters were calculated using ordinary least squares regression and fracture risk was assessed using Cox's models., Main Outcome: Incident low-trauma fracture ascertained by x-ray report., Results: Apart from lean mass in women, all muscle parameters declined over time. Greater rates of decline in physical performance were associated with increased fracture risk in women (Hazard ratios [HRs] ranging from 2.1 (95% CI: 1.5-2.9) for GS to 2.7 (95% CI: 1.9-3.6) for 5xSTS, while in men only the decline in GS was associated with fracture risk (HR: 3.4 [95% CI: 1.8-6.3]). Baseline performance and strength were also associated with increased fracture risk in men (HRs ranging from 1.8 (95% CI: 1.1-3.0) for QS to 2.5 (95% CI: 1.5-4.1) for TGUG, but not in women., Conclusion: Rate of decline in physical performance in both genders, and baseline strength and performance in men, contributed independently to fracture risk. Sit-to-stand and GS were the tests most consistently associated with fractures. Further studies are required to determine whether muscle strength and/or performance improve the predictive accuracy of fracture prediction models., (© Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: It has been assumed that, for a given BMI, Asians have higher percent body fat (PBF) than Caucasians. As a result, it has been suggested that the BMI threshold for diagnosing obesity in Asians be lowered to less than  30 kg/m 2 . This study sought to compare PBF between Koreans and Australians., Methods: Whole-body fat mass and PBF were measured in 1,211 Koreans and 1,006 Australians using dual-energy x-ray absorptiometry (Lunar Prodigy; GE Healthcare, Madison, Wisconsin). The two groups were then matched for age and BMI by the propensity score method., Results: For a given age and BMI, Koreans had lower PBF than Australians, and the difference was statistically significant in women (mean difference: -2.13%; 95% CI: -2.61% to -1.65%) but not in men (difference: -0.54%; 95% CI: -1.22% to 0.14%). Matched-pair analysis (423 pairs of women and 208 pairs of men) also showed that Korean women had statistically lower PBF than their Australian counterparts (P < 0.001)., Conclusions: In individuals aged 60 years and older, Koreans do not have higher PBF than Australians after adjusting for BMI. These results suggest that there is no evidence for lowering the BMI threshold for the diagnosis of obesity in elderly Koreans., (© 2019 The Obesity Society.)

Introduction: Osteoporosis is a systemic skeletal disease that is characterised by reduced bone strength and increased fracture risk. Osteoporosis-related fractures impose enormous disease and economic burden to the society. Although many treatments and health interventions are proven effective to prevent fractures, health economic evaluation adds evidence to their economic merits. Computer simulation modelling is a useful approach to extrapolate clinical and economic outcomes from clinical trials and it is increasingly used in health economic evaluation. Many osteoporosis health economic models have been developed in the past decades; however, they are limited to academic use and there are no publicly accessible health economic models of osteoporosis., Methods and Analysis: We will develop the Australian osteoporosis health economic model based on our previously published microsimulation model of osteoporosis in the Chinese population. The development of the model will follow the recommendations for the conduct of economic evaluations in osteoporosis by the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases and the US branch of the International Osteoporosis Foundation. The model will be a state-transition semi-Markov model with memory. Clinical parameters in the model will be mainly obtained from the Dubbo Osteoporosis Epidemiology Study and the health economic parameters will be collected from the Australian arm of the International Costs and Utilities Related to Osteoporotic Fractures Study. Model transparency and validates will be tested using the recommendations from Good Research Practices in Modelling Task Forces. The model will be used in economic evaluations of osteoporosis interventions including pharmaceutical treatments and primary care interventions. A user-friendly graphical user interface will be developed, which will connect the user to the calculation engine and the results will be generated. The user interface will facilitate the use of our model by people in different sectors., Ethics and Dissemination: No ethical approval is needed for this study. Results of the model validation and future economic evaluation studies will be submitted to journals. The user interface of the health economic model will be publicly available online accompanied with a user manual., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Research on non-communicable diseases (NCD) in Indigenous Australians has mostly focused on diabetes mellitus and chronic kidney or cardiovascular disease. Osteoporosis, characterised by low bone mass and structural deterioration of bone tissue, and sarcopenia, the age-related loss of muscle mass and strength, often co-exist with these common NCDs-the combination of which will disproportionately increase bone fragility and fracture risk and negatively influence cortical and trabecular bone. Furthermore, the social gradient of NCDs, including osteoporosis and fracture, is well-documented, meaning that specific population groups are likely to be at greater risk of poorer health outcomes: Indigenous Australians are one such group., Purpose: This review summarises the findings reported in the literature regarding the muscle and bone health of Indigenous Australians., Findings: There are limited data regarding the musculoskeletal health of Indigenous Australians; however, areal bone mineral density (aBMD) measured by dual-energy X-ray absorptiometry (DXA) is reported to be greater at the hip compared to non-Indigenous Australians. Falls are the leading cause of injury-related hospitalisations in older Australians, particularly Indigenous Australians, with a great proportion suffering from fall-related fractures. Despite sparse data, it appears that Indigenous men and women have a substantially higher risk of hip fracture at a much younger age compared to non-Indigenous Australians., Conclusion: Data on more detailed musculoskeletal health outcomes are required in Indigenous Australians to better understand fracture risk and to formulate evidence-based strategies for fracture prevention and to minimise the risk of falls.

Objectives: To determine the effect of two doses of intramuscular cholecalciferol on serial serum 25-hydroxy-vitamin-D levels and on pharmacodynamics endpoints: calcium, phosphate, parathyroid hormone, C-reactive protein, interleukin-6, and cathelicidin in critically ill adults., Design: Prospective randomized interventional study., Setting: Tertiary, academic adult ICU., Patients: Fifty critically ill adults with the systemic inflammatory response syndrome., Intervention: Patients were randomly allocated to receive a single intramuscular dose of either 150,000 IU (0.15 mU) or 300,000 IU (0.3 mU) cholecalciferol., Measurements and Main Results: Pharmacokinetic, pharmacodynamic parameters, and outcome measures were collected over a 14-day period or until ICU discharge, whichever was earlier. Prior to randomization, 28 of 50 patients (56%) were classified as vitamin D deficient. By day 7 after randomization, 15 of 23 (65%) and 14 of 21 patients (67%) normalized vitamin D levels with 0.15 and 0.3 mU, respectively (p=0.01) and by day 14, 8 of 10 (80%) and 10 of 12 patients (83%) (p=0.004), respectively. Secondary hyperparathyroidism was manifested in 28% of patients at baseline. Parathyroid hormone levels decreased over the study period with patients achieving vitamin D sufficiency at day 7 having significantly lower parathyroid hormone levels (p<0.01). Inflammatory markers (C-reactive protein and interleukin-6) fell significantly over the study period. Greater increments in 25-hydroxy-vitamin-D were significantly associated with greater increments in cathelicidin at days 1 and 3 (p=0.04 and 0.004, respectively). Although in-hospital mortality rate did not differ between the groups, patients who did not mount a parathyroid hormone response to vitamin D deficiency had a higher mortality (35% vs 12%; p=0.05). No significant adverse effects were observed., Conclusions: A single dose of either dose of intramuscular cholecalciferol corrected vitamin D deficiency in the majority of critically ill patients. Greater vitamin D increments were associated with early greater cathelicidin increases, suggesting a possible mechanism of vitamin D supplementation in inducing bactericidal pleiotropic effects.

Unlabelled: Lower body fat mass is a risk factor for bone loss at lumbar spine in postmenopausal women, but not in men. Body lean mass and fat mass were not associated with femoral neck bone loss in either gender., Introduction: Bone density and body mass are closely associated. Whole body lean mass (LM) and fat mass (FM) together account for approximately 95 % of body mass. Bone loss is associated with loss of body mass but which of the components of body mass (FM or LM) is related to bone loss is not well understood. Therefore, in this study, we sought to assess whether baseline FM or LM has predictive value for future relative rate of bone mineral density (BMD) changes (%/year)., Methods: The present population-based cohort study was part of the ongoing Dubbo Osteoporosis Epidemiology Study (DOES). BMD, FM, and LM were measured with dual energy X-ray absorptiometry (GE-LUNAR Corp, Madison, WI). BMD measurements were taken in approximately every 2 years between 2000 and 2010. We only included the participants with at least two BMD measurements at the femoral neck and lumbar spine. In total, 717 individuals (204 men and 513 women) aged 50 years or older were studied., Results: Rate of bone loss at femoral neck and lumbar spine was faster in women than in men (all P < 0.01). In bivariable regression analysis, each 5 kg greater FM in women was associated with 0.4 %/year (P = 0.003) lower bone loss at lumbar spine. This magnitude of association remained virtually unchanged after adjusting for LM and/or other covariates (P = 0.03). After adjusting for covariates, variation of FM accounted for ∼1.5 % total variation in lumbar spine bone loss. However, there was no significant association between FM and change in femoral neck BMD in either men or women., Conclusion: Lower FM was an independent but modest risk factor for greater bone loss at the lumbar spine in women but not in men. If further studies confirm our findings, FM can help predict lumbar spine bone loss in women.

After fracture there is increased risk of refracture and premature mortality. These outcomes, particularly premature mortality following refracture, have not previously been studied together to understand overall mortality risk. This study examined the long-term cumulative incidence of subsequent fracture and total mortality with mortality calculated as a compound risk and separated according to initial and refracture. Community-dwelling participants aged 60+ years from Dubbo Osteoporosis Epidemiology Study with incident fractures, followed prospectively for further fractures and deaths from 1989 to 2010. Subsequent fracture and mortality ascertained using cumulative incidence competing risk models allowing four possible outcomes: death without refracture; death following refracture; refracture but alive, and event-free. There were 952 women and 343 men with incident fracture. Within 5 years following initial fracture, 24% women and 20% men refractured; and 26% women and 37% men died without refracture. Of those who refractured, a further 50% of women and 75% of men died, so that total 5-year mortality was 39% in women and 51% in men. Excess mortality was 24% in women and 27% in men. Although mortality following refracture occurred predominantly in the first 5 years post-initial fracture, total mortality (post-initial and refracture) was elevated for 10 years. Most of the 5-year to 10-year excess mortality was associated with refracture. The long-term (>10 years) refracture rate was reduced, particularly in the elderly as a result of their high mortality rate. The 30% alive beyond 10 years postfracture were at low risk of further adverse outcomes. Refractures contribute substantially to overall mortality associated with fracture. The majority of the mortality and refractures occurred in the first 5 years following the initial fracture. However, excess mortality was observed for up to 10 years postfracture, predominantly related to that after refracture., (© 2013 American Society for Bone and Mineral Research.)

Low bone mineral density (BMD) is used as a parameter of osteoporosis. Genome-wide association studies of BMD have hitherto focused on BMD as a quantitative trait, yielding common variants of small effects that contribute to the population diversity in BMD. Here we use BMD as a dichotomous trait, searching for variants that may have a direct effect on the risk of pathologically low BMD rather than on the regulation of BMD in the healthy population. Through whole-genome sequencing of Icelandic individuals, we found a rare nonsense mutation within the leucine-rich-repeat-containing G-protein-coupled receptor 4 (LGR4) gene (c.376C>T) that is strongly associated with low BMD, and with osteoporotic fractures. This mutation leads to termination of LGR4 at position 126 and fully disrupts its function. The c.376C>T mutation is also associated with electrolyte imbalance, late onset of menarche and reduced testosterone levels, as well as an increased risk of squamous cell carcinoma of the skin and biliary tract cancer. Interestingly, the phenotype of carriers of the c.376C>T mutation overlaps that of Lgr4 mutant mice.

Bone mineral density (BMD) has been reported to be both higher and lower in Indigenous women from different populations. Body composition data have been reported for Indigenous Australians, but there are few published BMD data in this population. We assessed BMD in 161 Indigenous Australians, identified as Aboriginal (n=70), Torres Strait Islander (n=68) or both (n=23). BMD measurements were made on Norland-XR46 (n=107) and Hologic (n=90) dual-energy X-ray absorptiometry (DXA) machines. Norland BMD and body composition measurements in these individuals, and also in 36 Caucasian Australians, were converted to equivalent Hologic BMD (BMD(H)) and body composition measurements for comparison. Femoral neck (FN) and lumbar spine Z-scores were high in Indigenous participants (mean FN Z-score: Indigenous men +0.98, p<0.0001 vs. mean zero; Indigenous women +0.82, p<0.0001 vs. mean zero). FN BMD(H) was higher in Aboriginal and/or Torres Strait Islander than Caucasian participants, after adjusting for age, gender, diabetes and height and remained higher in men after addition of lean mass to the model. We conclude that FN BMD is higher in Aboriginal and/or Torres Strait Islander Australians than Caucasian Australian reference ranges and these differences still remained significant in men after adjustment for lean mass. It remains to be seen whether these BMD differences translate to differences in fracture rates., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Introduction: In animal model, mice treated with beta-blockers (BB) had increased bone mass. In humans, high bone mass is associated with reduce fracture risk. The present study sought to test the hypothesis that BB use is associated with reduced fracture risk., Materials and Methods: Data from 3488 participants (1285 men) aged 50 years and above in the Dubbo Osteoporosis Epidemiology Study (DOES) were analyzed. Baseline characteristics of participants were obtained at the initial visit which had taken place between 1989 and 1993. Bone mineral density (BMD) at the lumbar spine and femoral neck was measured by dual energy X-ray absorptiometry (GE-LUNAR Corp, Madison, WI). Two hundred and sixty two (20%) men and 411 (19%) women had been on BB, as ascertained by direct interview and verification with medication history. The incidence of fragility fractures was ascertained during the follow-up period (1989-2008)., Results: In men, BB use was associated with higher BMD at the femoral neck (0.96 versus 0.92 g/cm², P < 0.01), higher lumbar spine (1.32 versus 1.25 g/cm², P < 0.01), and lower fracture risk than those not on BB (odds ratio [OR]: 0.49; 95% CI: 0.32-0.75). In women, BB users also had higher femoral neck BMD (0.83 versus 0.81 g/cm², P < 0.01), higher lumbar spine BMD (1.11 versus 1.06 g/cm², P < 0.01), and lower risk of fracture than non-users (OR 0.68, 95% CI: 0.53-0.87). The associations between BB use and fracture risk were independent of age, BMD, and clinical risk factors. Subgroup analysis suggested that the association was mainly found in selective BB, not in non-selective BB., Conclusion: Beta-blockers use, particularly selective BB, was associated with reduced fracture risk in both men and women, and the association was independent of BMD., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Background: Bone mineral density influences the risk of osteoporosis later in life and is useful in the evaluation of the risk of fracture. We aimed to identify sequence variants associated with bone mineral density and fracture., Methods: We performed a quantitative trait analysis of data from 5861 Icelandic subjects (the discovery set), testing for an association between 301,019 single-nucleotide polymorphisms (SNPs) and bone mineral density of the hip and lumbar spine. We then tested for an association between 74 SNPs (most of which were implicated in the discovery set) at 32 loci in replication sets of Icelandic, Danish, and Australian subjects (4165, 2269, and 1491 subjects, respectively)., Results: Sequence variants in five genomic regions were significantly associated with bone mineral density in the discovery set and were confirmed in the replication sets (combined P values, 1.2x10(-7) to 2.0x10(-21)). Three regions are close to or within genes previously shown to be important to the biologic characteristics of bone: the receptor activator of nuclear factor-kappaB ligand gene (RANKL) (chromosomal location, 13q14), the osteoprotegerin gene (OPG) (8q24), and the estrogen receptor 1 gene (ESR1) (6q25). The two other regions are close to the zinc finger and BTB domain containing 40 gene (ZBTB40) (1p36) and the major histocompatibility complex region (6p21). The 1p36, 8q24, and 6p21 loci were also associated with osteoporotic fractures, as were loci at 18q21, close to the receptor activator of the nuclear factor-kappaB gene (RANK), and loci at 2p16 and 11p11., Conclusions: We have discovered common sequence variants that are consistently associated with bone mineral density and with low-trauma fractures in three populations of European descent. Although these variants alone are not clinically useful in the prediction of risk to the individual person, they provide insight into the biochemical pathways underlying osteoporosis., (Copyright 2008 Massachusetts Medical Society.)

Background: Cross-sectional studies from different populations show a variable decline in blood testosterone concentrations as men age. Few population representative cohorts have been followed up over time., Objective: The objective of the study was to quantify longitudinally the change in serum testosterone and SHBG concentrations with age in two well-defined, representative but geographically widely separated regional Australian cohorts., Subjects and Setting: The Busselton cohort comprises individuals aged 18-90 yr residing in Western Australia assessed prospectively since 1981. Sera were assayed from 910 men, from whom further samples were available 14 yr later in 480. The Dubbo cohort involves individuals aged 61-90 yr living in Eastern Australia. Baseline sera were collected from 610 men and additional sera on a second (n = 370) and third (n = 200) occasion from 1989 to 2004. Men from both cohorts are community dwelling and of predominately European origin., Results: Longitudinal analyses show the following: 1) total testosterone declines comparably (P > 0.9) by 1.3% (Busselton) and 0.9% (Dubbo) per annum with the same rates of decline when analyses were restricted to men older than 60 yr of age; 2) annual changes in SHBG were also very similar in age-restricted analyses (2.3% vs. 2.5%, P = 0.48); and 3) the annual increase in SHBG was steeper in middle-aged and older men (P < 10(-3) vs. young men). These longitudinal changes were all up to 4-fold greater in magnitude, compared with cross-sectional analyses of baseline data., Conclusion: In two separate regional Australian populations, blood testosterone fell and SHBG increased comparably with age. Age-related changes in blood testosterone and SHBG previously described in urban-dwelling men are the same in men who reside in smaller regional cities of another continent.

Unlabelled: In this 14-year prospective study, men and women were found to share a common set of risk factors for hip fracture: low BMD, postural instability and/or quadriceps weakness, a history of falls, and prior fracture. The combination of these risk factors accounted for 57% and 37% of hip fractures in women and men, respectively., Introduction: Risk factors for hip fracture, including low BMD, identified in women, have not been shown to be useful in men. It is also not known whether fall-related factors (muscle strength and postural instability) predict hip fracture. This study examined the association between falls-related factors and hip fractures in elderly men and women., Materials and Methods: This is an epidemiologic, community-based prospective study, which included 960 women and 689 men > or = 60 years of age who have been followed for a median of 12 years (interquartile range, 6-13). The number of person-years was 9961 for women and 4463 for men. The outcome measure was incidence of hip fracture. Risk factors were femoral neck BMD (FNBMD), postural sway, quadriceps strength, prior fracture, and fall., Results: Between 1989 and 2003, 115 (86 women) sustained a hip fracture. The risk of hip fracture (as measured by hazards ratio [HR]) was increased by 3.6-fold (95% CI: 2.6-4.5) in women and 3.4-fold (95% CI: 2.5-4.6) in men for each SD (0.12 g/cm2) reduction in FNBMD. After adjusting for BMD, the risk of hip fracture was also increased in individuals with the highest tertile of postural sway (HR: 2.7; 95% CI: 1.6-4.5) and low tertiles of quadriceps strength (HR: 3.0; 95% CI: 1.3-6.8). Furthermore, a history of fall during the preceding 12 months and a history of fracture were independent predictors of hip fracture. For each level of BMD, the risk of hip fracture increased linearly with the number of non-BMD risk factors. Approximately 57% and 37% of hip fracture cases in women and men, respectively, were attributable to the presence of risk factors, osteoporosis (BMD T score < or = -2.5), and advancing age., Conclusions: Men and women had a common set of risk factors for hip fracture: low BMD, postural instability and/or quadriceps weakness, a history of falls, and prior fracture. Preventive strategies should simultaneously target reducing falls and improvement of bone strength in both men and women.

Low testosterone has been associated with hip fracture in men in some studies. However, data on other hormonal parameters and fracture outcome in men is minimal. This study examined the association between free testosterone (free T) estradiol (E2), sex hormone-binding globulin (SHBG), 25-hydroxyvitamin D [25(OH)D], parathyroid hormone (PTH), insulin-like growth factor I (IGF-I), and fracture in 437 elderly community-dwelling men. Age, height, weight, quadriceps strength, femoral neck bone mineral density (FN BMD), and fracture data (1989-1997) also were obtained. Fractures were classified as major (hip, pelvis, proximal tibia, multiple rib, vertebral, and proximal humerus) or minor (remaining distal upper and lower limb fractures). Fifty-four subjects had a fracture (24 major and 30 minor). There was no association between minor fractures and any hormonal parameter. Risk of major fracture was increased 2-fold for each SD increase in age, decrease in weight and height, and increase in SHBG, and risk of major fracture was increased 3-fold for each SD decrease in quadriceps strength, FN BMD, and 25(OH)D (univariate logistic regression). Independent predictors of major fracture were FN BMD, 2.7 (1.5-4.7; odds ratio [OR]) and 95% confidence interval [CI]); 25(OH)D, 2.8 (1.5-5.3); and SHBG, 1.7 (1.2-2.4). An abnormal value for three factors resulted in a 30-fold increase in risk but only affected 2% of the population. It is not immediately apparent how 25(OH)D and SHBG, largely independently of BMD, may contribute to fracture risk. They may be markers for biological age or health status not measured by methods that are more traditional and as such may be useful in identifying those at high risk of fracture.

Dietary calcium intake and physical activity are considered practical measures for prevention of osteoporosis. However, their associations with bone mineral density (BMD) in the elderly are not clear. The present study examined the association between osteoporosis and these two factors in relation to body mass index (BMI) in a cross-sectional, epidemiological study involving 1075 women and 690 men, aged 69 +/- 6.7 years (mean +/- SD). Dietary calcium intake (median of 580 mg/day) was inversely related to age (p = 0.01), positively related to physical activity index (PAI) (p = 0.01), femoral neck BMD (p = 0.01) in women, and higher lumbar spine (p = 0.003) and femoral neck BMD (p = 0.03) in men. Quadriceps strength was negatively associated with age (p < 0.0001) and positively related to BMI (p < 0.0001) and BMD (p < 0.0001) in both men and women. The PAI was associated with quadriceps strength (p < 0.0001) and femoral neck and lumbar spine BMD in women (p < 0.001) and with femoral neck BMD in men (p = 0.04); however, these associations were not significant after adjusting for age, BMI, quadriceps strength, and dietary calcium. Women in the top tertile of quadriceps strength (> or =23 kg) and dietary calcium intake (> or =710 mg/day) had 15% higher BMD than those in the lowest tertiles (< or =15 kg and < or =465 mg/day); the difference was comparable in men (11%). Among subjects with the lowest tertiles of BMI (< or =23 kg/m2 for women and < or =24 kg/m2 for men), quadriceps strength (< or =15 kg for women and < or =28 kg for men), and dietary calcium intake (< or =465 mg/day), 64% and 40% of women and men, respectively, were classified as having osteoporosis (based on a 2.5-SD reduction from the young-normal mean). The prevalence was only 12% in women and 1.5% in men among those in the highest tertiles of the three factors. Adequate dietary calcium intake and maintaining a physically active lifestyle in late decades of life could potentially translate into a reduction in the risk of osteoporosis and hence improve the quality and perhaps quantity of life in the elderly population.