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Aim: To study the association between femoral neck (FN) bone mineral density (BMD) T-score and fracture risk in individuals with and without type 2 diabetes (T2D)., Materials and Methods: We performed a single-centre retrospective cohort study using the Danish National Health Service. BMD of the FN was measured by dual-energy X-ray absorptiometry. Cox proportional hazards regression models were used to study the association between FN BMD T-score and fractures in individuals with and without T2D separately, adjusted for age, comorbidities and comedication. The results from this analysis were used to estimate the 10-year absolute fracture risk., Results: In total, there were 35,129 women (2362 with T2D) and 7069 men (758 with T2D). The FN BMD T-score was significantly associated with risk of any, hip and major osteoporotic fracture in men and women with [adjusted hazard risk ratios (aHR) women, hip: 1.57; 95% confidence interval (CI) 1.24-2.00, incidence rate (IR) 8.7; aHR men, hip: 1.55; 95% CI 1.01-2.36, IR 4.6] and without T2D (aHR women, hip: 1.75; 95% CI 1.64-1.87, IR 7.0; aHR men, hip: 1.97, 95% CI 1.73-2.25, IR 6.3), and its ability to predict fracture risk was similar. Fracture IRs were not significantly different for individuals with or without T2D, nor was the estimated cumulative 10-year fracture risk., Conclusions: The FN BMD T-score was significantly associated with hip, non-spine and major osteoporotic fracture risk in men and women with and without T2D. Fracture risk for a given T-score and age was equal in individuals with and without T2D, as was the ability of the FN BMD T-score to predict fracture risk., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Purpose: To identify the optimal statistical approach for predicting the risk of fragility fractures in the presence of competing event of death., Methods: We used real-world data from the Dubbo Osteoporosis Epidemiology Study that has monitored 3035 elderly participants for bone health and mortality. Fragility fractures were ascertained radiologically. Mortality was confirmed by the State Registry. We considered four statistical models for predicting fracture risk: (i) conventional Cox's proportional hazard model, (ii) cause-specific model, (iii) Fine-Gray sub-distribution model, and (iv) multistate model. These models were fitted and validated in the development (60% of the original sample) and validation (40%) subsets, respectively. The model performance was assessed by discrimination and calibration analyses., Results: During a median follow-up of 11.3 years (IQR: 7.2, 16.2), 628 individuals (34.5%) in the development cohort fractured, and 630 (34.6%) died without a fracture. Neither the discrimination nor the 5-year prediction performance was significantly different among the models, though the conventional model tended to overestimate fracture risk (calibration-in-the-large index =  - 0.24; 95% CI: - 0.43, - 0.06). For 10-year risk prediction, the multistate model (calibration-in-the-large index =  - 0.05; 95% CI: - 0.20, 0.10) outperformed the cause-specific (- 0.23; - 0.30, - 0.08), Fine-Gray (- 0.31; - 0.46, - 0.16), and conventional model (- 0.54; - 0.70, - 0.39) which significantly overestimated fracture risk., Conclusion: Adjustment for competing risk of death has minimum impact on the short-term prediction of fracture. However, the multistate model yields the most accurate prediction of long-term fracture risk and should be considered for predictive research in the elderly, who are also at high mortality risk. Fracture risk assessment might be compromised by the competing event of death. This study, using real-world data found a multistate model was superior to the current competing risk methods in fracture risk assessment. A multistate model is considered an optimal statistical method for predictive research in the elderly., (© 2024. The Author(s).)

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.)

The relationship between self-reported falls and fracture risk was estimated in an international meta-analysis of individual-level data from 46 prospective cohorts. Previous falls were associated with an increased fracture risk in women and men and should be considered as an additional risk factor in the FRAX® algorithm., Introduction: Previous falls are a well-documented risk factor for subsequent fracture but have not yet been incorporated into the FRAX algorithm. The aim of this study was to evaluate, in an international meta-analysis, the association between previous falls and subsequent fracture risk and its relation to sex, age, duration of follow-up, and bone mineral density (BMD)., Methods: The resource comprised 906,359 women and men (66.9% female) from 46 prospective cohorts. Previous falls were uniformly defined as any fall occurring during the previous year in 43 cohorts; the remaining three cohorts had a different question construct. The association between previous falls and fracture risk (any clinical fracture, osteoporotic fracture, major osteoporotic fracture, and hip fracture) was examined using an extension of the Poisson regression model in each cohort and each sex, followed by random-effects meta-analyses of the weighted beta coefficients., Results: Falls in the past year were reported in 21.4% of individuals. During a follow-up of 9,102,207 person-years, 87,352 fractures occurred of which 19,509 were hip fractures. A previous fall was associated with a significantly increased risk of any clinical fracture both in women (hazard ratio (HR) 1.42, 95% confidence interval (CI) 1.33-1.51) and men (HR 1.53, 95% CI 1.41-1.67). The HRs were of similar magnitude for osteoporotic, major osteoporotic fracture, and hip fracture. Sex significantly modified the association between previous fall and fracture risk, with predictive values being higher in men than in women (e.g., for major osteoporotic fracture, HR 1.53 (95% CI 1.27-1.84) in men vs. HR 1.32 (95% CI 1.20-1.45) in women, P for interaction = 0.013). The HRs associated with previous falls decreased with age in women and with duration of follow-up in men and women for most fracture outcomes. There was no evidence of an interaction between falls and BMD for fracture risk. Subsequent risk for a major osteoporotic fracture increased with each additional previous fall in women and men., Conclusions: A previous self-reported fall confers an increased risk of fracture that is largely independent of BMD. Previous falls should be considered as an additional risk factor in future iterations of FRAX to improve fracture risk prediction., (© 2024. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

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).)

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 β-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., (© 2023. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

Context: Fragility fracture is a significant public health problem because it is associated with increased mortality. We want to find out whether the risk of fracture can be predicted from the time of birth., Objective: To examine the association between a polygenic risk score (PRS) and lifetime fracture risk., Methods: This population-based prospective study involved 3515 community-dwelling individuals aged 60+ years who have been followed for up to 20 years. Femoral neck bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry. A PRS was created by summing the weighted number of risk alleles for each single nucleotide polymorphism using BMD-associated coefficients. Fragility fractures were radiologically ascertained, whereas mortality was ascertained through a state registry. Residual lifetime risk of fracture (RLRF) was estimated by survival analysis., Results: The mortality-adjusted RLRF for women and men was 36% (95% CI, 34%-39%) and 21% (18%-24%), respectively. Individuals with PRS > 4.24 (median) had a greater risk (1.2-fold in women and 1.1-fold in men) than the population average risk. For hip fracture, the average RLRF was 10% (95% CI, 8%-12%) for women and ∼5% (3%-7%) for men; however, the risk was significantly increased by 1.5-fold and 1.3-fold for women and men with high PRS, respectively., Conclusion: A genetic profiling of BMD-associated genetic variants is associated with the residual lifetime risk of fracture, suggesting the potential for incorporating the polygenic risk score in personalized fracture risk assessment., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Osteoporotic fractures present a major health problem with an increasing prevalence in older people. Fractures are associated with premature mortality, reduced quality of life, subsequent fracture, and increased costs. Hence, it is crucial to identify those at higher risk of fracture. Fracture risk assessment tools incorporated clinical risk factors to improve fracture predictive power over BMD alone. However, fracture risk prediction using these algorithms remains suboptimal, warranting further improvement. Muscle strength and physical performance measurements have been associated with fracture risk. In contrast, the contribution of sarcopenia, the composite condition of low muscle mass, muscle strength and/or physical performance, to fracture risk is unclear. It is uncertain whether this is due to the problematic definition of sarcopenia per se or limitations of the diagnostic tools and cut-off points of the muscle mass component. The recent position statement from the Sarcopenia Definition and Outcomes Consortium confirmed the inclusion of muscle strength and performance in the definition of sarcopenia but not DXA-assessed lean mass. Therefore, clinicians should focus on functional assessment (muscle strength and performance) rather than muscle mass, at least as assessed by DXA, as predictors of fractures. Muscle strength and performance are modifiable risk factors. Resistance exercise improves muscle parameters in the elderly, potentially leading to reduced risk of falls and fractures in the general population and in those who sustained a fracture. Therapists may consider exercise intervention to improve muscle parameters and potentially reduce the risk of fractures. The aim of this review was to explore 1) the contribution of muscle parameters (i.e., muscle mass, strength, and physical performance) to fracture risk in older adults, and 2) the added predictive accuracy of these parameters beyond the existing fracture assessment tools. These topics provide the rationale for investigating strength and physical performance interventions to reduce fracture risk. Most of the included publications showed that muscle mass is not a good predictor of fracture risk, while poor muscle strength and performance are associated with an increased risk of fracture, particularly in men, independent of age, BMD, and other risk factors for fractures. Muscle strength and performance can potentially improve the predictive accuracy in men beyond that obtained by the fracture risk assessment tools, Garvan FRC and FRAX., Competing Interests: Declaration of competing interest Alajlouni, Bliuc, and Tran declare that they have no conflict of interest or personal relationships in relation to this work. Blank declares having received personal fees from Bristol-Myers Squibb Company, stock ownership in Abbott Laboratories, AbbVie, Amgen Inc., GSK PLC, Johnson & Johnson, and Procter & Gamble Company, served on the advisory board of Amgen Inc., and ownership interest in JangoBio outside the submitted work; received an editorial stipend from Elsevier; received royalties from Wolters Kluwer NV; and served on the board of the Asia-Pacific Fragility Fracture Alliance; served as treasurer of the International Federation of Musculoskeletal Research Societies and the International Society for Clinical Densitometry. Center declares having received personal fees for educational talks from Amgen Inc. and Actavis Generics and served on the advisory boards of Amgen Inc. and Bayer AG outside the submitted work., (Copyright © 2023 Elsevier Inc. All rights reserved.)

This qualitative study interviewed general practitioners, patients, and FLS clinicians and identified key challenges facing stakeholders seeking to improve post-fracture osteoporosis care. Local policies and care pathways as an initial strategy may address information and service delivery issues across the acute-primary care divide., Introduction: Fracture liaison services (FLS) can be effective for secondary fracture prevention, but long-term adherence to therapies remains suboptimal. Few studies have explored how services manage the transition between tertiary and primary post-fracture care. This study mapped service processes and factors influencing integration of post-clinic care, identifying barriers, supports, and opportunities for seamless healthcare., Methods: Qualitative descriptive study using semi-structured interviews with FLS stakeholders at two metropolitan hospitals in New South Wales (NSW) and surrounding general practices., Results: Seven FLS clinicians, 11 general practitioners (GPs), and seven patients were interviewed. Six key themes emerged on the transition of patient care from tertiary to primary care (PC). Interprofessional communication issues and role ambiguity posed threats to seamless care. Delayed, absent, inaccessible, or poor-quality communication frustrated GPs, while FLS clinicians lacked confidence in existing communication systems and desired bidirectional communication with PC. GPs were confident managing osteoporosis, but FLS clinicians had limited confidence that patients would discuss osteoporosis with their GP and that GPs would action recommendations. Effective PC follow-up required a positive GP-patient relationship and that patients perceived a need to engage with PC. Patient understanding of osteoporosis (influenced by patient education, knowledge, beliefs, and health behaviours) affected PC attendance. Limited public awareness of osteoporosis and healthcare policy deficits contributed to care gaps., Conclusion: Key challenges were identified facing stakeholders seeking to improving post-clinic osteoporosis care. Development and implementation of local, integrated acute-community policies and care pathways as an initial intervention may address information and service delivery issues across the acute-PC divide., (© 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.)

Importance: Limited knowledge about interactions among health disorders impedes optimal patient care. Because comorbidities are common among patients 50 years and older with fractures, these fractures provide a useful setting for studying interactions among disorders., Objective: To define multimorbidity clusters at the time of fracture and quantify the interaction between multimorbidity and fracture in association with postfracture excess mortality., Design, Setting, and Participants: This nationwide cohort study included 307 870 adults in Denmark born on or before January 1, 1951, who had an incident low-trauma fracture between January 1, 2001, and December 31, 2014, and were followed up through December 31, 2016. Data were analyzed from February 1 to March 31, 2022., Main Outcomes and Measures: Fracture and 32 predefined chronic diseases recorded within 5 years before the index fracture were identified from the Danish National Hospital Discharge Register. Death was ascertained from the Danish Register on Causes of Death. Latent class analysis was conducted to identify multimorbidity clusters. Relative survival analysis was used to quantify excess mortality associated with the combination of multimorbidity and fractures at specific sites., Results: Among the 307 870 participants identified with incident fractures, 95 372 were men (31.0%; mean [SD] age at fracture, 72.3 [11.2] years) and 212 498 were women (69.0%; mean [SD] age at fracture, 74.9 [11.2] years). During a median of 6.5 (IQR, 3.0-11.0) years of follow-up, 41 017 men (43.0%) and 81 727 women (38.5%) died. Almost half of patients with fractures (42.9%) had at least 2 comorbidities. Comorbidities at fracture were categorized as low-multimorbidity (60.5% in men and 66.5% in women), cardiovascular (23.7% in men and 23.5% in women), diabetic (5.6% in men and 5.0% in women), malignant (5.1% in men and 5.0% in women), and mixed hepatic and/or inflammatory (5.1% in men only) clusters. These clusters distinguished individuals with advanced, complex, or late-stage disease from those with earlier-stage disease. Multimorbidity and proximal or lower leg fractures were associated with increased mortality risk, with the highest excess mortality found in patients with hip fracture in the malignant cluster (1-year excess mortality: 40.8% [95% CI: 38.1%-43.6%]). The combination of multimorbidity and fracture compounded the association with mortality, conferring much greater risk than either alone., Conclusions and Relevance: Concomitant illnesses were common and clustered into distinct multimorbidity clusters that were associated with excess postfracture mortality. The compound contribution of multimorbidity to postfracture excess mortality highlights the need for more comprehensive approaches in these high-risk patients. The analytical approach applied to fracture could also be used to examine other sentinel health events.

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))., (© 2022. International Osteoporosis Foundation and National Osteoporosis Foundation.)

Fracture liaison services (FLS) are considered to be the most effective organizational approach for secondary fracture prevention. In this study, we evaluated whether FLS care was associated with reduced subsequent fracture and mortality risk over 3 years of follow-up. In total, 8682 consecutive patients aged 50-90 years with a recent fracture were included. Before FLS introduction, regular fracture treatment procedures were followed (pre-FLS). After FLS introduction, patients were invited to the FLS and FLS attenders were assessed for osteoporosis, prevalent vertebral fractures, metabolic bone disorders, medication use, and fall risk, and treatment for fracture prevention was initiated according to Dutch guidelines. All fractures were radiographically confirmed and categorized into major/hip (pelvis, proximal humerus or tibia, vertebral, multiple rib, distal femur) and non-major/non-hip (all other fractures). Mortality risk was examined using age and sex adjusted Cox proportional hazard models. For subsequent fracture risk, Cox proportional hazard models were adjusted for age, sex, and competing mortality risk (subdistribution hazard [SHR] approach). The pre-FLS group consisted of 2530 patients (72% women), of whom 1188 (46.9%) had major/hip index fractures, the post-FLS group consisted of 6152 patients (69% women), of whom 2973 (48.3%) had major/hip index fractures. In patients with a non-major/non-hip fracture there was no difference in subsequent non-major/non-hip fracture risk or mortality between pre-FLS and post-FLS. In patients with a major/hip index fracture, mortality risk was lower post-FLS (hazard ratio [HR] 0.84; 95% confidence interval [CI], 0.73-0.96) and subsequent major/hip fracture risk was lower in the first 360 days after index fracture post-FLS compared to pre-FLS (SHR 0.67; 95% CI, 0.52-0.87). In conclusion, FLS care was associated with a lower mortality risk in the first 3 years and a lower subsequent major/hip fracture risk in the first year in patients with a major/hip index fracture but not in patients with a non-major/non-hip fracture. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)., (© 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).)

Muscle strength and physical performance are associated with incident fractures and mortality. However, their role in the risk of subsequent fracture and postfracture mortality is not clear. We assessed the association between muscle strength (grip strength) and performance (gait speed and chair stands time) and the risk of subsequent fracture and mortality in 830 men with low-trauma index fracture, who participated in the Osteoporotic Fractures in Men (MrOS) USA Study and had their index measurements assessed within 5 years prior to the index fracture. The annual decline in muscle strength and performance following index fracture, estimated using linear mixed-effects regression, was also examined in relation to mortality. The associations were assessed using Cox proportional hazards models adjusted for age, femoral neck bone mineral density (FN BMD), prior fractures, falls, body mass index (BMI), index fracture site, lifestyle factors, and comorbidities. Over a median follow-up of 3.7 (interquartile range [IQR], 1.3-8.1) years from index fracture to subsequent fracture, 201 (24%) men had a subsequent fracture and over 5.1 (IQR, 1.8-9.6) years to death, and 536 (65%) men died. Index measurements were not associated with subsequent fracture (hazard ratios [HRs] ranging from 0.97 to 1.07). However, they were associated with postfracture mortality. HR (95% confidence interval [CI]) per 1 standard deviation (1-SD) decrement in grip strength: HR 1.12 (95% CI, 1.01-1.25) and gait speed: HR 1.14 (95% CI, 1.02-1.27), and 1-SD increment in chair stands time: HR 1.08 (95% CI, 0.97-1.21). Greater annual declines in these measurements were associated with higher mortality risk, independent of the index values and other covariates. HR (95% CI) per 1-SD annual decrement in change in grip strength: HR 1.15 (95% CI, 1.01-1.33) and in gait speed: HR 1.38 (95% CI, 1.13-1.68), and 1-SD annual increment in chair stands time: HR 1.28 (95% CI, 1.07-1.54). Men who were unable to complete one or multiple tests had greater risk of postfracture mortality (24%-109%) compared to those performed all tests. It remains to be seen whether improvement in these modifiable factors can reduce postfracture mortality. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)., (© 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).)

Objectives: To evaluate the risk of subsequent fractures in patients who attended the Fracture Liaison Service (FLS), with and without incident falls after the index fracture., Design: A 3-year prospective observational cohort study., Setting: An outpatient FLS in the Netherlands., Participants: Patients aged 50+ years with a recent clinical fracture., Outcome Measures: Incident falls and subsequent fractures., Results: The study included 488 patients (71.9% women, mean age: 64.6±8.6 years). During the 3-year follow-up, 959 falls had been ascertained in 296 patients (60.7%) (ie, fallers), and 60 subsequent fractures were ascertained in 53 patients (10.9%). Of the fractures, 47 (78.3%) were fall related, of which 25 (53.2%) were sustained at the first fall incident at a median of 34 weeks. An incident fall was associated with an approximately 9-fold (HR: 8.6, 95% CI 3.1 to 23.8) increase in the risk of subsequent fractures., Conclusion: These data suggest that subsequent fractures among patients on treatment prescribed in an FLS setting are common, and that an incident fall is a strong predictor of subsequent fracture risk. Immediate attention for fall risk could be beneficial in an FLS model of care., Trial Registration Number: NL45707.072.13., Competing Interests: Competing interests: LV, CEW, RYVdV, HMJJ, SK, JD, JE, TT and DB have nothing to disclose. JRC reports honoraria for educational talks and part support for educational meetings from Amgen, and advisory board participation for Amgen and Bayer, outside the submitted work. TVN reports honoraria for lectures sponsored from Merck and participation as executive member Asia Pacific Consortium on Osteoporosis, outside the submitted work. PG reports grants from Amgen, Pfizer, MSD, UCB, Abbott, Lilly, BMS, Novartis, Roche and Will Pharma, and honoraria for lectures from Amgen and Lilly, outside the submitted work. JPvdB reports grants for lectures from UCB and Amgen, outside the submitted work., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Diabetes and fractures are both associated with increased mortality, however the effect of the combination is not well-established. We examined the mortality risk following all types of fractures in type 2 diabetes (T2D)., Methods: In the Dubbo Osteoporosis Epidemiology Study (1989-2017), participants were grouped according to T2D and/or incident fracture. Study outcome was all-cause mortality. First incident radiological fragility fracture and incident T2D diagnosis were time-dependent variables. Cox's proportional hazards models quantified mortality risk associated with T2D and incident fracture overall, as well as by fracture site, T2D duration and T2D medication type., Results: In 3618 participants (62% women), 272 had baseline and 179 developed T2D over median 13.0 years (IQR 8.2-19.6). 796 women (56 with T2D) and 240 men (25 with T2D) sustained a fracture. Compared to those without T2D or fracture, mortality risk increased progressively, in T2D without fracture, then no T2D with fracture, and was highest in those with T2D with fracture (adjusted hazard ratio (aHR) (95% CI) for women 2.62 (1.75-3.93) and men 2.61 (1.42-4.81)). Within T2D participants, incident fracture was associated with increased mortality (aHR for women 1.87 (1.10-3.16) and men 2.83 (1.41-5.68)), especially following hip/vertebral fractures in men (aHR 2.97 (1.29-6.83)) and non-hip non-vertebral fractures in women (aHR 2.42 (1.24-4.75)), and in T2D duration >5 years., Conclusion: Any fracture in T2D conferred significant excess mortality. Individuals with T2D should be carefully monitored post-fracture, especially if T2D >5 years. Optimising fracture prevention and post-fracture management in T2D is critical and warrants further studies., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Muscle strength and physical performance are associated with fracture risk in men. However, it is not known whether these measurements enhance fracture prediction beyond Garvan and FRAX tools. A total of 5665 community-dwelling men, aged ≥65 years, from the Osteoporotic Fractures in Men (MrOS) Study, who had data on muscle strength (grip strength) and physical performance (gait speed and chair stand tests), were followed from 2000 to 2019 for any fracture, major osteoporotic fracture (MOF), initial hip, and any hip fracture. The contributions to different fracture outcomes were assessed using Cox's proportional hazard models. Tool-specific analysis approaches and outcome definitions were used. The added predictive values of muscle strength and physical performance beyond Garvan and FRAX were assessed using categorical net reclassification improvement (NRI) and relative importance analyses. During a median follow-up of 13 (interquartile range 7-17) years, there were 1014 fractures, 536 MOFs, 215 initial hip, and 274 any hip fractures. Grip strength and chair stand improved prediction of any fracture (NRI for grip strength 3.9% and for chair stand 3.2%) and MOF (5.2% and 6.1%). Gait speed improved prediction of initial hip (5.7%) and any hip (7.0%) fracture. Combining grip strength and the relevant performance test further improved the models (5.7%, 8.9%, 9.4%, and 7.0% for any, MOF, initial, and any hip fractures, respectively). The improvements were predominantly driven by reclassification of those with fracture to higher risk categories. Apart from age and femoral neck bone mineral density, muscle strength and performance were ranked equal to or better than the other risk factors included in fracture models, including prior fractures, falls, smoking, alcohol, and glucocorticoid use. Muscle strength and performance measurements improved fracture risk prediction in men beyond Garvan and FRAX. They were as or more important than other established risk factors. These measures should be considered for inclusion in fracture risk assessment tools. © 2021 American Society for Bone and Mineral Research (ASBMR)., (© 2021 American Society for Bone and Mineral Research (ASBMR).)

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.)

Text-search software can be used to identify people at risk of re-fracture. The software studied identified a threefold higher number of people with fractures compared with conventional case finding. Automated software could assist fracture liaison services to identify more people at risk than traditional case finding., Purpose: Fracture liaison services address the post-fracture treatment gap in osteoporosis (OP). Natural language processing (NLP) is able to identify previously unrecognized patients by screening large volumes of radiology reports. The aim of this study was to compare an NLP software tool, XRAIT (X-Ray Artificial Intelligence Tool), with a traditional fracture liaison service at its development site (Prince of Wales Hospital [POWH], Sydney) and externally validate it in an adjudicated cohort from the Dubbo Osteoporosis Epidemiology Study (DOES)., Methods: XRAIT searches radiology reports for fracture-related terms. At the development site (POWH), XRAIT and a blinded fracture liaison clinician (FLC) reviewed 5,089 reports and 224 presentations, respectively, of people 50 years or over during a simultaneous 3-month period. In the external cohort of DOES, XRAIT was used without modification to analyse digitally readable radiology reports (n = 327) to calculate its sensitivity and specificity., Results: XRAIT flagged 433 fractures after searching 5,089 reports (421 true fractures, positive predictive value of 97%). It identified more than a threefold higher number of fractures (421 fractures/339 individuals) compared with manual case finding (98 individuals). Unadjusted for the local reporting style in an external cohort (DOES), XRAIT had a sensitivity of 70% and specificity of 92%., Conclusion: XRAIT identifies significantly more clinically significant fractures than manual case finding. High specificity in an untrained cohort suggests that it could be used at other sites. Automated methods of fracture identification may assist fracture liaison services so that limited resources can be spent on treatment rather than case finding.

Osteoporotic vertebral compression fractures (VCFs) are a risk factor for morbidity and mortality, frequently asymptomatic and often present in computed tomography (CT) scans performed for unrelated conditions. Computer-aided diagnosis (CAD) of VCF from such images can potentially improve identification and treatment of osteoporosis. This single-blinded, single tertiary center study compared a CAD (Zebra Medical Vision®) to an adjudicated imaging specialist reevaluation using a retrospective consecutive sample of abdominal and thoracic CT scans (n = 2357) performed as part of routine care. Subjects over 50 years between January 1, 2019 and May 12, 2019 were included. Duplicates and unanalyzable scans were excluded resulting in a total of 1696 CT scans. The sensitivity, specificity, and accuracy were calculated for all VCF and for Genant grades 2 or 3 (ie, height loss of >25%) using imaging specialist as the gold standard. Prestudy VCF reporting by hospital-rostered radiologist was used to calculate the number of scans needed to screen (NNS) to detect one additional VCF using CAD. Prevalence of any VCF was 24% (406/1696) and of Genant 2/3 VCF was 18% (280/1570). The sensitivity and specificity were 54% and 92%, for all fractures, respectively, and 65% and 92% for Genant 2/3 fractures, respectively. Accuracy for any VCF, and for detection of Genant 2/3 VCF, was 83% and 88%, respectively. Of 221 CAD-detected VCFs, 133 (60.2%) were reported prestudy resulting in 88 additional fractures (72 Genant 2/3) being identified by CAD. NNS to detect one additional VCF was 19 scans for all fractures and 23 for Genant 2/3 fractures. Thus, the CAD tested in this study had a high specificity with moderate sensitivity to detect incidental vertebral fractures in CT scans performed for routine care. A low NNS suggests it is an efficient tool to assist radiologists and clinicians to improve detection and reporting of vertebral fractures. © 2020 American Society for Bone and Mineral Research (ASBMR)., (© 2020 American Society for Bone and Mineral Research (ASBMR).)

Aim: To investigate the utility of calcaneal quantitative ultrasound compared with bone densitometry (DXA) in predicting incident low-trauma fracture in type 2 diabetes., Methods: This retrospective cohort study included a subset of participants in the Dubbo Osteoporosis Epidemiology Study who had concurrent calcaneal quantitative ultrasound and DXA measurement, comprising 809 people without type 2 diabetes and 96 with type 2 diabetes. Fracture data had been collected prospectively. Cox proportional hazard models and receiver operating curves (ROC) were used to compare calcaneal quantitative ultrasound and DXA parameters as predictors for any low-trauma fracture., Results: The median age of participants was 71 years (IQR 68-76, 50% men) for those without type 2 diabetes and 70 years (IQR 68-76, 55% men) for those with type 2 diabetes. There was no difference in low-trauma fracture incidence between groups when stratified by sex. In those without type 2 diabetes, the hazard ratio for fracture per 1 sd decrease in broadband ultrasound attenuation and femoral neck bone mineral density (BMD) was 1.47 [95% confidence interval (CI) 1.26-1.71] and 1.39 (95% CI 1.17-1.64), respectively. The corresponding figures in type 2 diabetes were 1.81 (95% CI 1.03-3.19) for broadband ultrasound attenuation and 2.55 (95% CI 1.28-5.08) for femoral neck BMD., Conclusion: Broadband ultrasound attenuation is comparable with femoral neck BMD as a predictor for low trauma incident fracture in type 2 diabetes. Calcaneal quantitative ultrasound offers several advantages over DXA and should be considered in further studies of bone health screening or in clinical practice where DXA is unavailable., (© 2019 Diabetes UK.)

Existing fracture risk assessment tools are not designed to predict fracture-associated consequences, possibly contributing to the current undermanagement of fragility fractures worldwide. We aimed to develop a risk assessment tool for predicting the conceptual risk of fragility fractures and its consequences. The study involved 8965 people aged ≥60 years from the Dubbo Osteoporosis Epidemiology Study and the Canadian Multicentre Osteoporosis Study. Incident fracture was identified from X-ray reports and questionnaires, and death was ascertained though contact with a family member or obituary review. We used a multistate model to quantify the effects of the predictors on the transition risks to an initial and subsequent incident fracture and mortality, accounting for their complex interrelationships, confounding effects, and death as a competing risk. There were 2364 initial fractures, 755 subsequent fractures, and 3300 deaths during a median follow-up of 13 years (interquartile range [IQR] 7-15). The prediction model included sex, age, bone mineral density, history of falls within 12 previous months, prior fracture after the age of 50 years, cardiovascular diseases, diabetes mellitus, chronic pulmonary diseases, hypertension, and cancer. The model accurately predicted fragility fractures up to 11 years of follow-up and post-fracture mortality up to 9 years, ranging from 7 years after hip fractures to 15 years after non-hip fractures. For example, a 70-year-old woman with a T-score of -1.5 and without other risk factors would have 10% chance of sustaining a fracture and an 8% risk of dying in 5 years. However, after an initial fracture, her risk of sustaining another fracture or dying doubles to 33%, ranging from 26% after a distal to 42% post hip fracture. A robust statistical technique was used to develop a prediction model for individualization of progression to fracture and its consequences, facilitating informed decision making about risk and thus treatment for individuals with different risk profiles. © 2020 American Society for Bone and Mineral Research., (© 2020 American Society for Bone and Mineral Research.)

Less is known about the impact of non-hip non-vertebral fractures (NHNV) on early death. This study demonstrated increased risk of dying following hip and NHNV fractures which was further increased by a subsequent fracture. This highlights the importance of early intervention to prevent both initial and subsequent fractures and improve survival., Introduction: Osteoporotic fractures are a major health concern. Limited evidence exists on their impact on mortality in ageing populations. This study examined the contribution of initial fracture type and subsequent fracture on mortality in a Norwegian population that has one of the highest rates of fractures., Methods: The Tromsø Study is a prospective population-based cohort in Norway. Women and men aged 50+ years were followed from 1994 to 2010. All incident hip and non-hip non-vertebral (NHNV) fractures were registered. NHNV fractures were classified as either proximal or distal. Information on self-reported co-morbidities, lifestyle factors, general health and education level was collected. Multivariable Cox models were used to quantify mortality risk with incident and subsequent fractures analysed as time-dependent variables., Results: Of 5214 women and 4620 men, 1549 (30%) and 504 (11%) sustained a fracture, followed by 589 (38%) and 254 (51%) deaths over 10,523 and 2821 person-years, respectively. There were 403 (26%) subsequent fractures in women and 68 (13%) in men. Hip fracture was associated with a two-fold increase in mortality risk (HR 2.05, 95% CI 1.73-2.42 in women and 2.49, 95% CI 2.00-3.11 in men). Proximal NHNV fractures were associated with 49% and 81% increased mortality risk in women and men (HR 1.49, 95% CI 1.21-1.84 and 1.81, 95% CI 1.37-2.41), respectively. Distal NHNV fractures were not associated with mortality. Subsequent fracture was associated with 89% and 77% increased mortality risk in women and men (HR 1.89, 95% CI 1.52-2.35 and 1.77, 95% CI 1.16-2.71), respectively., Conclusion: Hip, proximal NHNV and subsequent fractures were significantly associated with increased mortality risk in the elderly, highlighting the importance of early intervention.

In this prospective cohort of 6120 participants aged 50+, nitrogen-bisphosphonates but not non-nitrogen bisphosphonates were associated with a significant 34% mortality risk reduction compared to non-treated propensity score matched controls. These findings open new avenues for research into mechanistic pathways., Introduction: Emerging evidence suggests that bisphosphonates (BP), first-line treatment of osteoporosis, are associated with reduced risks for all-cause mortality. This study aimed to determine the association between different BP types and mortality risk in participants with or without a fracture., Methods: A prospective cohort study of users of different BPs matched to non-users by propensity score (age, gender, co-morbidities, fragility fracture status) and time to starting the BP medication from the population-based Canadian Multicentre Osteoporosis Study from nine Canadian centres followed from 1995 to 2013. Mortality risk for bisphosphonate users vs matched non-users was assessed using pairwise multivariable Cox proportional hazards models., Results: There were 2048 women and 308 men on BP and 1970 women and 1794 men who did not receive medication for osteoporosis. The relationship between BP and mortality risk was explored in three separate 1:1 propensity score-matched cohorts of BP users and no treatment (etidronate, n = 599, alendronate, n = 498, and risedronate n = 213). Nitrogen BP (n-BP) (alendronate and risedronate) was associated with lower mortality risks [pairwise HR, 0.66 (95% CI, 0.48-0.91)] while the less potent non-n-BP, etidronate, was not [pairwise HR: 0.89 (95% CI, 0.66-1.20)]. A direct comparison between n-BP and etidronate (n = 340 pairs) also suggested a better survival for n-BP [paired HR, 0.47 (95%CI, (95% CI, 031-0.70)] for n-BP vs. etidronate]., Conclusion: Compared to no treatment, nitrogen but not non-nitrogen bisphosphonates appear to be associated with better survival.

Context: Little is known about long-term excess mortality following fragility nonhip fractures., Objective: The study aimed to determine which fracture was associated with excess mortality and for how long the postfracture excess mortality persisted., Design, Setting, and Patients: This nationwide registry-based follow-up study included all individuals in Denmark aged 50+ years who first experienced fragility fractures in 2001 and were followed up for up to 10 years for their mortality risk., Main Outcome Measure: The contribution of fracture to mortality at precise postfracture time intervals was examined using relative survival analysis, accounting for time-related mortality changes in the background population., Results: There were 21,123 women (aged 72 ± 13 years) and 9481 men (aged 67 ± 12 years) with an incident fragility fracture in 2001, followed by 10,668 and 4745 deaths, respectively. Excess mortality was observed following all proximal and lower leg fractures. The majority of deaths occurred within the first year after fracture, and thereafter excess mortality gradually declined. Hip fractures were associated with the highest excess mortality (33% and 20% at 1 year after fracture in men and women, respectively). One-year excess mortality after fracture of a femur or pelvis was 20% to 25%; vertebrae, 10%; humerus, rib, or clavicle, 5% to 10%; and lower leg, 3%. A significant although smaller excess mortality was still observed until 10 years for hip fractures and ~5 years after femur, other proximal, and lower leg fractures., Conclusion: This study highlights the important contribution of a wide variety of fragility fractures to long-term excess mortality and thus the potential for benefit from early intervention.

Objective: Osteoporotic fragility fractures, that are common in men and women, signal increased risk of future fractures and of premature mortality. Less than one-third of postmenopausal women and fewer men are prescribed active treatments to reduce fracture risk. Therefore, in this study the association of oral bisphosphonate recommendation with subsequent fracture and mortality over eight years in a fracture liaison service setting was analysed., Materials and Methods: In this prospective cohort study, 5011 men and women aged >50 years, who sustained a clinical fracture, accepted the invitation to attend the fracture liaison service of the West Glasgow health service between 1999 and 2007. These patients were fully assessed and all were recommended calcium and vitamin D. Based on pre-defined fracture risk criteria, 2534 (50.7%) patients were additionally also recommended oral bisphosphonates. Mortality and subsequent fracture risk were the pre-defined outcomes analysed using Cox proportional hazard models., Results: Those recommended bisphosphonates were more often female (82.9 vs. 72.4%), were older (73.4 vs. 64.4 years), had lower bone mineral density T-score (-3.1 vs. -1.5) and more had sustained hip fractures (21.7 vs. 6.2%; p < 0.001). After adjustments, patients recommended bisphosphonates had lower subsequent fracture risk (Hazard Ratio (HR): 0.60; 95% confidence interval (CI): 0.49-0.73) and lower mortality risk (HR: 0.79, 95%CI: 0.64-0.97)., Conclusion: Of the patients, who are fully assessed after a fracture at the fracture liaison service, those with higher fracture risk and a recommendation for bisphosphonates had worse baseline characteristics. However, after adjusting for these differences, those recommended bisphosphonate treatment had a substantially lower risk for subsequent fragility fracture and lower risk for mortality. These community-based data indicate the adverse public health outcomes and mortality impacts of the current low treatment levels post fracture could be improved by bisphosphonate recommendation for both subsequent fracture and mortality., Competing Interests: Dr. van Geel, Dr. Bliuc, Prof. Geusens, Prof. Dinant, dr. Tran, and Prof. McLellan have no competing of interests to report. Prof. Center discloses relevant financial interests outside this body of work. She has received honoraria for educational talks and meeting sponsorship from Amgen, Teva, and Merck Sharpe and Dohme. She has received honoraria for educational talks and meeting sponsorship from Amgen and Merck Sharpe and Dohme. Prof. van den Bergh discloses relevant financial interests outside this body of work. He has received honoraria for educational talks and grants from Amgen, Merck, Sharp and Dohme, Eli Lilly and Will Pharma. Prof. Eisman discloses relevant financial interests outside this body of work. He has received grants and/or personal fees from Amgen, Merck, Sharp and Dohme, Novartis, and sanofi-Aventis and non-financial support from Aspen. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Femoral neck (FN) bone mineral density (BMD) is the most commonly used skeletal site to estimate fracture risk. The role of lumbar spine (LS) BMD in fracture risk prediction is less clear due to osteophytes that spuriously increase LS BMD, particularly at lower levels. The aim of this study was to compare fracture predictive ability of upper L1-L2 BMD with standard L2-L4 BMD and assess whether the addition of either LS site could improve fracture prediction over FN BMD. This study comprised a prospective cohort of 3016 women and men over 60 yr from the Dubbo Osteoporosis Epidemiology Study followed up for occurrence of minimal trauma fractures from 1989 to 2014. Dual-energy X-ray absorptiometry was used to measure BMD at L1-L2, L2-L4, and FN at baseline. Fracture risks were estimated using Cox proportional hazards models separately for each site. Predictive performances were compared using receiver operating characteristic curve analyses. There were 565 women and 179 men with a minimal trauma fracture during a mean of 11 ± 7 yr. L1-L2 BMD T-score was significantly lower than L2-L4 T-score in both genders (p < 0.0001). L1-L2 and L2-L4 BMD models had a similar fracture predictive ability. LS BMD was better than FN BMD in predicting vertebral fracture risk in women [area under the curve 0.73 (95% confidence interval, 0.68-0.79) vs 0.68 (95% confidence interval, 0.62-0.74), but FN was superior for hip fractures prediction in both women and men. The addition of L1-L2 or L2-L4 to FN BMD in women increased overall and vertebral predictive power compared with FN BMD alone by 1% and 4%, respectively (p < 0.05). In an elderly population, L1-L2 is as good as but not better than L2-L4 site in predicting fracture risk. The addition of LS BMD to FN BMD provided a modest additional benefit in overall fracture risk. Further studies in individuals with spinal degenerative disease are needed., (Copyright © 2017 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.)

Osteoporosis (OP) causes reduced bone strength and increases risk of fractures. Medical records from specialist clinics in Japan of postmenopausal women with OP and high risk of fracture were analysed. Majority of patients were treated for OP as recommended and were prescribed OP medications soon after high-risk OP diagnosis., Purpose: The incidence of osteoporosis (OP) in Japan is predicted to increase significantly in coming decades. Resultant osteoporotic fractures are a significant contributor of economic and social burden among elderly osteoporosis patients. This retrospective chart review was conducted as a response to the current evidence gap in the treatment patterns for OP patients with high risk of fracture in Japan., Methods: This was a multi-centre retrospective chart review that analysed data extracted from the medical records of postmenopausal OP patients at high risk for fracture who received care at 11 specialist clinics and medical centers in Japan for at least 18 to 24 months. Main outcome was OP treatment patterns., Results: The study included 709 eligible patients of whom 623 (87.9%) were prescribed OP medication during the study period. The most common reason for not taking OP medication was patient unwillingness to take medication. The most common OP medications prescribed initially were minodronic acid (20.1%), alendronate (19.9%), raloxifene (14.1%), weekly teriparatide acetate (12.4%) and eldecalcitol (11.4%). Majority of patients (62.1%) were still taking their initial medication at the end of the 18-24 month follow-up., Conclusions: A high percentage of patients (87.9%) in Japan received OP medications soon after their high-risk diagnosis, with bisphosphonates, selective estrogen receptor modulators and teriparatide being the predominant treatment options.

Purpose of the Review: This review aims to highlight important clinical findings from the over 25 year-long Dubbo Osteoporosis Epidemiology Study particularly focusing on outcomes post fracture., Recent Findings: Every low trauma fracture in the elderly is associated with an increased risk of a subsequent fracture, with a higher risk in men than women. All major or proximal fractures and even minor fractures in the very elderly or minor fractures that are then followed by re-fracture are associated with premature mortality, greatest in the first 5 years post fracture. Having a subsequent fracture further increases this high mortality risk, but if an individual survives the high risk period, their risk returns to that of the background population. Non-hip non-vertebral fractures account for a significant proportion of the premature mortality. Despite an improvement in overall health and population mortality over the years, excess mortality post fracture has not changed in the last 2 decades. All low trauma, fractures in the elderly herald a high risk of poor outcomes, particularly in the first few years post fracture. Early intervention should be initiated.

Few studies have examined the relationship between more-than-minimal-trauma fractures and bone density. This study demonstrated that more-than-minimal-trauma fractures are associated with lower bone density similar to that seen in minimal trauma fractures. Men and women over 50 years with a more-than-minimal-trauma fracture should be investigated to exclude low bone density., Introduction: The aim of this study was to assess the prevalence and predictors of low bone density in men and women with more-than-minimal-trauma fractures., Methods: In an Australian hospital, 630 community-dwelling men and women, 20 years of age or older, sustained a fracture due to more-than-minimal-trauma (force greater than a fall from standing height but less than high trauma). We studied 349 individuals who agreed to have a bone mineral density (BMD) scan. These participants were compared with 472 men and women with minimal trauma fractures., Results: Men and women with more-than-minimal-trauma fractures had significantly lower bone density than expected for their age, gender and weight (Z-score spine  = -0.4 SD, 95 % confidence interval (CI), -0.5 to -0.3; Z-score hip  = -0.5 SD, 95 % CI, -0.6 to -0.4). Almost 1 in 4 of those over 50 years of age had osteoporosis by BMD criteria. The independent predictors of low bone density (T-score <-2.0 SD) were age equal to or over 50 years (odds ratio (OR) = 5.97, 95 % CI, 3.34 to 10.65), low body weight <20 kg/m 2 (OR = 3.44, 95 % CI, 1.32 to 8.94), a prior minimal trauma fracture (OR = 2.76, 95 % CI, 1.17-6.52) and in those over 50 years of age, an osteoporosis-associated condition (OR = 4.51, 95 % CI, 1.69 to 12.06). Men and women with more-than-minimal-trauma fractures had similar bone density (Z-score) compared to those with minimal trauma fractures., Conclusions: Men and women over 50 years with a more-than-minimal-trauma fracture, especially those with low body weight, prior minimal trauma fracture or an osteoporosis-associated condition, should be investigated to exclude low bone density and its associated risk of subsequent fractures.

Purpose of Review: Increased mortality risk is accepted for hip and vertebral fracture. Recent data suggest that other fracture types have also been linked to excess mortality. This article reviews the existing evidence on the pattern and determinants of postfracture mortality., Recent Findings: The pattern of mortality over time following hip and vertebral fractures has recently been clarified. Nonhip nonvertebral fractures at major, and even minor sites in older individuals have also been associated with excess mortality. Studies have revealed the higher excess mortality in men and in younger age groups for all fracture types. Despite the increasing knowledge on the fracture-mortality association, little is known about its cause. The role of co-morbidities is inconsistent across studies. Recent findings suggest low bone mass, bone loss and muscle weakness are linked to both fracture and mortality risk, and thus may play a role in postfracture mortality., Summary: Nonhip nonvertebral fractures have recently been associated with mortality risk. Larger studies are needed to better understand which specific fractures and factors contribute to fracture-associated mortality risk. The role of bone loss in postfracture mortality needs to be validated in more studies, because of its potential reversibility with antifracture therapies.

Context: Hip fracture incidence has been declining and life expectancy improving. However, trends of postfracture outcomes are unknown., Objectives: The objective of the study was to compare the refracture risk and excess mortality after osteoporotic fracture between two birth cohorts, over 2 decades., Design: Prospective birth cohorts were followed up over 2 decades (1989-2004 and 2000-2014)., Setting: The study was conducted in community-dwelling participants in Dubbo, Australia., Participants: Women and men aged 60-80 years, participating in Dubbo Osteoporosis Epidemiology Study 1 (DOES 1; born before 1930) and Dubbo Osteoporosis Epidemiology Study 2 (DOES 2; born after 1930) participated in the study., Main Outcome Measure: Age-standardized fracture and mortality over two time intervals: (1989-2004 [DOES 1] and 2000-2014 [DOES 2]) were measured., Results: The DOES 2 cohort had higher body mass index and bone mineral density and lower initial fracture rate than DOES 1, but similar refracture rates [age-standardized refracture rates per 1000 person-years: women: 53 (95% confidence interval [CI] 42-63) and 51 (95% CI 41-60) and men: 53 (95% CI 38-69) and 55 (95% CI 40-71) for DOES 2 and DOES 1, respectively). Absolute postfracture mortality rates declined in DOES 2 compared with DOES 1, mirroring the improvement in general-population life expectancy. However, when compared with period-specific general-population mortality, there was a similar 2.1- to 2.6-fold increased mortality risk after a fracture in both cohorts (age-adjusted standardized mortality ratio, women: 2.05 [95% CI 1.43-2.83] and 2.43 [95% CI 1.95-2.99] and men: 2.56 [95% CI 1.78-3.58] and 2.48 [95% CI 1.87-3.22] for DOES 2 and DOES 1, respectively)., Conclusion: Over the 2 decades, despite the decline in the prevalence of fracture risk factors, general-population mortality, and initial fracture incidence, there was no improvement in postfracture outcomes. Refracture rates were similar and fracture-associated mortality was 2-fold higher than expected. These data indicate that the low postfracture treatment rates are still a major problem.

Unlabelled: Bone loss, a fracture risk factor, may play a role in post-fracture mortality. We found accelerated bone loss (≥1.31 % bone loss/year for women and ≥1.35 % bone loss/year for men) associated with 44-77 % increased mortality. It remains unclear whether bone loss is a marker or plays a role in mortality., Introduction: Osteoporotic fractures are associated with increased mortality although the cause is unknown. Bone loss, a risk factor for osteoporotic fracture is also associated with increased mortality, but its role in mortality risk post-fracture is unclear. This study aimed to examine post-fracture mortality risk according to levels of bone loss., Methods: Community-dwelling participants aged 60+ from Dubbo Osteoporosis Epidemiology Study with incident fractures were followed from 1989 to 2011. Kaplan-Meier survival curves were constructed according to bone loss quartiles. Cox proportional hazard models were used to determine the effect of bone loss on mortality., Results: There were 341 women and 106 men with ≥2 BMD measurements. The rate of bone loss was similar for women and men (women mean -0.79 %/year, highest bone loss quartile -1.31 %/year; men mean -0.74 %/year, highest quartile -1.35 %/year). Survival was lowest for the highest quartile of bone loss for women (p < 0.005) and men (p = 0.05). When analysed by fracture type, the association of bone loss with mortality was observed for vertebral (highest vs lower 3 quartiles of bone loss, women p = 0.03 and men p = 0.02) and non-hip non-vertebral fractures in women (p < 0.0001). Bone loss did not play an additional role in mortality risk following hip fractures. Importantly, overall, rapid bone loss was associated with 44-77 % increased mortality risk after multiple variable adjustment., Conclusion: Rapid bone loss was an independent predictor of post-fracture mortality risk in both women and men. The association of bone loss and post-fracture mortality was predominantly observed following vertebral fracture in both women and men and non-hip non-vertebral fracture in women. It remains to be determined whether bone loss is a marker or plays a role in the mortality associated with fractures.

Objective: High body mass index (BMI) is associated with increased risk of osteoarthritis (OA) and reduced risk of fragility fracture. However, the relationship between fragility fracture and OA remained unclear. This study sought to investigate the effect of bone mineral density (BMD) in the OA-fracture relationship., Methods: Data from 2412 women and 1452 men aged >45 years in the Dubbo Osteoporosis Epidemiology Study (DOES) were analyzed. Individuals have been followed for up to 22 years (median: 7.5 years; range: 0.1-22 years). Femoral neck BMD (FNBMD) and lumbar spine BMD (LSBMD) was measured by dual energy X-ray absorptiometry (DXA) (GE LUNAR, Madison, WI). The presence of OA was ascertained at baseline by self-reported diagnosis. The incidence of low-trauma fracture was ascertained from X-ray reports., Results: Overall, 29% of women and 26% of men had reported a diagnosis of OA. Fracture risk was significantly higher in women with OA than those without OA (Hazard ratio (HR) = 1.50; 95% confidence interval (CI), 1.28-1.76). However, the association was mainly observed in women with osteopenic BMD (HR = 1.74; 95% CI, 1.38-2.17) and normal-BMD (HR = 1.50; 95% CI, 1.06-2.13) and not in those with osteoporosis. Further analysis revealed that osteopenic women with OA had significant increase in risk of vertebral (HR = 1.85; 95% CI, 1.24-2.75) and limb fracture (HR = 2.49; 95% CI, 1.77-3.48), but not in hip fracture. In men, no comparable relationship was found before and after adjustment for covariates., Conclusion: Women with OA have an increased risk of fragility fracture, and the risk was mainly observed in non-osteoporotic group., (Copyright © 2014 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Context: Nonhip nonvertebral fractures represent half of all osteoporotic fractures; however, their contribution to the burden of refracture and premature mortality is unclear., Objectives: To examine the risk and burden of subsequent fracture and mortality associated with an initial nonhip nonvertebral fracture., Setting and Participants: This is a prospective cohort from the Dubbo Osteoporosis Epidemiology Study, 1989-2010 of community dwelling participants aged 60+ with incident fractures., Outcome Measures: Relative risk of all subsequent fractures and age-adjusted standardized mortality ratios were calculated according to initial fracture type. The total burden of adverse events was assessed using competing risk models with four potential outcomes: mortality after initial fracture, mortality after subsequent fracture, subsequent fracture and alive, or event-free., Results: Of the 952 fractures in women and 343 in men, over half were nonhip nonvertebral fractures (486 in women and 173 in men). Nonhip nonvertebral fractures were associated with increased risk of any subsequent fracture (1.95 [1.67-2.27] for women and 2.47 [1.82-3.35] for men), hip refracture (2.11 [1.04-4.28] for women and 2.63 [1.35-5.13] for men), and vertebral refracture (1.89 [1.43-2.48] for women and 2.13 [1.20-3.79] for men). More importantly, nonhip nonvertebral fractures were associated overall with 20% excess mortality for the first 5 years postfracture, of which approximately half were due to initial fracture and the remaining due to subsequent fractures. Proximal fractures were associated with increased mortality risk per se, whereas distal fractures were associated with increased mortality risk only in the group who sustained subsequent fractures., Conclusion: Nonhip nonvertebral fractures are associated with significant risk of subsequent fracture including hip and vertebral refracture, and premature mortality. Due to their high prevalence, about half of all subsequent fractures and a quarter of all fracture-related excess mortality were attributable to nonhip nonvertebral fracture. Thus nonhip nonvertebral fracture warrants early investigation and appropriate intervention.

Unlabelled: Hypertension is an independent risk factor for osteoporosis and osteoporotic fracture in postmenopausal women., Introduction: Although hypertension has been suggested to be associated with increased fracture risk, it is not clear whether the association is independent of bone mineral density (BMD). The present study sought to examine the interrelationships between hypertension, BMD, and fracture risk., Methods: The study included 1,032 men and 1,701 women aged 50 years and older who were participants in the Dubbo Osteoporosis Epidemiology Study. BMD at the femoral neck and lumbar spine was measured by dual energy X-ray absorptiometry (GE-LUNAR Corp., Madison, WI, USA). The presence of hypertension was ascertained by direct interview and verification through clinical history. The incidence of fragility fractures was ascertained by X-ray report during the follow-up period (1989-2008). The Cox proportional hazards model was used to assess the association between hypertension and fracture risk., Results: Women with hypertension had lower BMD at the femoral neck (0.79 versus 0.82 g/cm(2), P = 0.02) than those without the disease. After adjusting for BMD and covariates, hypertension was an independent risk factor for fragility fracture [hazard ratio (HR), 1.49; 95% CI, 1.13-1.96]. In men, hypertension was associated with higher femoral neck BMD (0.94 versus 0.92 g/cm(2), P = 0.02), but the association between hypertension and fracture risk did not reach statistical significance., Conclusion: Hypertension is associated with increased fracture risk in women, and the association is independent of BMD.

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.)

Purpose of Review: Fragility fracture is a major public health burden, because it is associated with a substantial morbidity and mortality. Risk prediction models, including the Fracture Risk Assessment Tool (FRAX) and Garvan Fracture Risk Calculator (GFRC), have been developed to provide a useful clinical framework for communicating the risk of fracture. The present review examines the validation of risk prediction models in osteoporosis and identifies some major challenges., Recent Findings: Recent validation studies suggested that the area under the ROC curve in fracture discrimination ranged from 0.61 to 0.83 for FRAX, and from 0.63 to 0.88 for GFRC, with hip fracture having a better discrimination than fragility fractures as a group. FRAX substantially underestimated the risk of fracture, whereas the predicted risk by GFRC was close to or slightly higher than the actual risk. Results of post-hoc analyses of clinical trials indicated the antifracture efficacy of alendronate, coronate, bazedoxifene, and denosumab was greater in patients with higher predicted risk of fracture. However, there was no correlation between antifracture efficacy and predicted fracture risk among patients on raloxifene and strontium ranelate., Summary: The prognostic performance of FRAX and GFRC for fracture prediction is not perfect, but these predictive models can aid patients and doctors to communicate about fracture risk in the medium term and to make rational decisions. However, the application of these predictive models in making decisions for an individual should take into account the individual's perception of the importance of the risk of fracture and its severity outcomes.

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.

Most people presenting with incident osteoporotic fractures are neither assessed nor treated for osteoporosis to reduce their risk of further fractures, despite the availability of effective treatments. We evaluated the effectiveness of published models of care for the secondary prevention of osteoporotic fractures. We searched eight medical literature databases to identify reports published between 1996 and 2011, describing models of care for secondary fracture prevention. Information extracted from each publication included study design, patient characteristics, identification strategies, assessment and treatment initiation strategies, as well as outcome measures (rates of bone mineral density (BMD) testing, osteoporosis treatment initiation, adherence, re-fractures and cost-effectiveness). Meta-analyses of studies with valid control groups were conducted for two outcome measures: BMD testing and osteoporosis treatment initiation. Out of 574 references, 42 articles were identified as analysable. These studies were grouped into four general models of care-type A: identification, assessment and treatment of patients as part of the service; type B: similar to A, without treatment initiation; type C: alerting patients plus primary care physicians; and type D: patient education only. Meta-regressions revealed a trend towards increased BMD testing (p = 0.06) and treatment initiation (p = 0.03) with increasing intensity of intervention. One type A service with a valid control group showed a significant decrease in re-fractures. Types A and B services were cost-effective, although definition of cost-effectiveness varied between studies. Fully coordinated, intensive models of care for secondary fracture prevention are more effective in improving patient outcomes than approaches involving alerts and/or education only.

Background: Osteoporotic vertebral fractures are, as the hip fractures, associated with increased morbidity and mortality. Norway has one of the highest reported incidences of hip fractures in the world. Because of methodological challenges, vertebral fractures are not extensively studied. The aim of this population based study was to describe, for the first time, the age- and sex specific occurrence of osteoporotic vertebral fractures in Norway., Methods: Data was collected in the Tromso Study, 2007/8 survey. By the use of dual x-ray absorptiometry (GE Lunar Prodigy) vertebral fracture assessments were performed in 2887 women and men aged from 38 to 87 years, in addition to measurements of bone mineral density at the femoral sites. Information on lifestyle was collected through questionnaires. Comparisons between fractures and non-fractures were done sex stratified, by univariate analyses, adjusting for age when relevant., Results: The prevalence of vertebral fractures varied from about 3% in the age group below 60 to about 19% in the 70+ group in women, and from 7.5% to about 20% in men, with an overall prevalence of 11.8% in women and 13.8% in men (p = 0.07). Among those with fractures, only one fracture was the most common; two and more fractures were present in approximately 30% of the cases. Fractures were seen from the fourth lumbar to the fifth thoracic vertebrae, most common between first lumbar and sixth thoracic vertebrae. The most common type of fracture was the wedge type in both sexes. Bone mineral density at the hip differed significantly according to type of fracture, being highest in those with wedge fractures and lowest in those with compression fractures., Conclusions: The prevalence of vertebral fractures increased by age in women and men, but the overall prevalence was lower than expected, considering the high prevalence of hip and forearm fractures in Norway. In both sexes, the wedge type was the fracture type most frequently observed and most common in the thoracic region.

Objectives: Previous fracture prediction models have been based on the assumption of a stable risk of subsequent fractures over time. The aim of the present work was to develop a nomogram for prediction of 5-year and 10-year individualised absolute fracture risks for postmenopausal women taking into account the time relation between fractures., Methods: A population-based prospective study was performed in 23 general practice centres located in the southern part of The Netherlands. At baseline (1992-1994), 4203 postmenopausal women between 50 and 80 years participated and 2372 of them also participated 10 years later. Baseline measurements included lumbar spine bone mineral density (BMD) and clinical risk factor evaluation. The incidence of fractures was ascertained. Bayesian model averaging and Cox's proportional hazards model were used., Results: After enrolment, 382 (16.1%) women had a clinical fracture. Fracture risk was associated with advancing age (HR 1.09 per SD (5 years); 95% CI 1.01 to 1.17), lumbar spine BMD (HR 1.23 per -1 SD; 95% CI 1.10 to 1.37) and a prior fracture, with HR 3.27 (95% CI 2.50 to 4.30) for a recent prior fracture (≤5 years previously) and HR 1.97 (95% CI 1.43 to 2.71) for a non-recent prior fracture after menopause (>5 years previously). Women with a recent prior fracture had 66% higher risk of an incident fracture than those with a non-recent prior fracture (HR 1.66; 95% CI 1.15 to 2.40)., Conclusions: The nomogram developed can help doctors to inform patients more effectively and thus better manage patient care by providing an individualised fracture risk taking into account the time relationship for fractures.

Nonvertebral fractures form the bulk of osteoporotic fractures and yet, other than hip fractures, are often dismissed, particularly in the younger age groups. Thus, less than 30% of women with osteoporotic fractures and less than 10% of men worldwide are receiving appropriate treatment. This article discusses the incidence, cost, and consequences of nonvertebral fractures. Recent evidence suggests these fractures form the bulk of costs to the community and herald an increased risk of refracture and premature mortality that applies to all types of nonvertebral, and not just hip, fractures.

Unlabelled: We evaluated the prognostic accuracy of fracture risk assessment tool (FRAX) and Garvan algorithms in an independent Australian cohort. The results suggest comparable performance in women but relatively poor fracture risk discrimination in men by FRAX. These data emphasize the importance of external validation before widespread clinical implementation of prognostic tools in different cohorts., Introduction: Absolute risk assessment is now recognized as a preferred approach to guide treatment decision. The present study sought to evaluate accuracy of the FRAX and Garvan algorithms for predicting absolute risk of osteoporotic fracture (hip, spine, humerus, or wrist), defined as major in FRAX, in a clinical setting in Australia., Methods: A retrospective validation study was conducted in 144 women (69 fractures and 75 controls) and 56 men (31 fractures and 25 controls) aged between 60 and 90 years. Relevant clinical data prior to fracture event were ascertained. Based on these variables, predicted 10-year probabilities of major fracture were calculated from the Garvan and FRAX algorithms, using US (FRAX-US) and UK databases (FRAX-UK). Area under the receiver operating characteristic curves (AUC) was computed for each model., Results: In women, the average 10-year probability of major fracture was consistently higher in the fracture than in the nonfracture group: Garvan (0.33 vs. 0.15), FRAX-US (0.30 vs. 0.19), and FRAX-UK (0.17 vs. 0.10). In men, although the Garvan model yielded higher average probability of major fracture in the fracture group (0.32 vs. 0.14), the FRAX algorithm did not: FRAX-US (0.17 vs. 0.19) and FRAX-UK (0.09 vs. 0.12). In women, AUC for the Garvan, FRAX-US, and FRAX-UK algorithms were 0.84, 0.77, and 0.78, respectively, vs. 0.76, 0.54, and 0.57, respectively, in men., Conclusion: In this analysis, although both approaches were reasonably accurate in women, FRAX discriminated fracture risk poorly in men. These data support the concept that all algorithms need external validation before clinical implementation.