A profiling analysis of contributions of cigarette smoking, dietary calcium intakes, and physical activity to fragility fracture in the elderly

Fragility fracture and bone mineral density (BMD) are influenced by common and modifiable lifestyle factors. In this study, we sought to define the contribution of lifestyle factors to fracture risk by using a profiling approach. The study involved 1683 women and 1010 men (50+ years old, followed up for up to 20 years). The incidence of new fractures was ascertained by X-ray reports. A “lifestyle risk score” (LRS) was derived as the weighted sum of effects of dietary calcium intake, physical activity index, and cigarette smoking. Each individual had a unique LRS, with higher scores being associated with a healthier lifestyle. Baseline values of lifestyle factors were assessed. In either men or women, individuals with a fracture had a significantly lower age-adjusted LRS than those without a fracture. In men, each unit lower in LRS was associated with a 66% increase in the risk of total fracture (non-adjusted hazard ratio [HR] 1.66; 95% CI, 1.26 to 2.20) and still significant after adjusting for age, weight or BMD. However, in women, the association was uncertain (HR 1.30; 95% CI, 1.11 to 1.53). These data suggest that unhealthy lifestyle habits are associated with an increased risk of fracture in men, but not in women, and that the association is mediated by BMD

Reduced mortality and subsequent fracture risk associated with oral bisphosphonate recommendation in a fracture liaison service setting: A prospective cohort study

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 \u3e50 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 \u3c 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

KBG syndrome presenting with brachydactyly type E

We report the case of a young woman who presented at age 10 years with height on the tenth centile, brachydactyly type E and mild developmental delay. Biochemistry and hormonal profiles were normal. Differential diagnoses considered included Albright hereditary osteodystrophy without hormone resistance (a.k.a pseudopseudohypoparathyroidism), 2q37 microdeletion syndrome and acrodysostosis. She had a normal karyotype and normal FISH of 2q37. Whole genome sequencing (WGS) identified a mutation in the ANKRD11 gene associated with KBG syndrome. We review the clinical features of the genetic syndromes considered, and suggest KBG syndrome be considered in patients presenting with syndromic brachydactyly type E, especially if short stature and developmental delay are also present

Microsimulation model for the health economic evaluation of osteoporosis interventions: Study protocol

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 semiMarkov 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

Relationship between serum testosterone and fracture risk in men: a comparison of RIA and LC-MS/MS

BACKGROUND: Serum testosterone can be measured byLC-MS/MS and RIA. We investigated whether the testosterone–fracture relationship was affected by the method of measurement. METHODS: We measured total testosterone (TT) by LCMS/MS (TTLC-MS/MS) and RIA (TTRIA) in serum samples collected from 602 men whose incident fractures had been continuously ascertained by x-ray reports from 1989 to 2010. We measured bone mineral density (BMD) by dual-energy x-ray absorptiometry. The association between TT and fracture risk was assessed by the Cox proportional hazards model, taking into account the effect of age and BMD. CONCLUSIONS: The concordance between LC-MS/MS and RIA in the measurement of serum TT was moderate. Moreover, the magnitude of association between testosterone and fracture risk in older men was largely unaffected by the method of measurement. © 2015 American Association for Clinical Chemistr

Epidemiological transition to mortality and refracture following an initial fracture

This study sought to redefine the concept of fracture risk that includes refracture and mortality, and to transform the risk into "skeletal age". We analysed data obtained from 3521 women and men aged 60 years and older, whose fracture incidence, mortality, and bone mineral density (BMD) have been monitored since 1989. During the 20-year follow-up period, among 632 women and 184 men with a first incident fracture, the risk of sustaining a second fracture was higher in women (36%) than in men (22%), but mortality risk was higher in men (41%) than in women (25%). The increased risk of mortality was not only present with an initial fracture, but was accelerated with refractures. Key predictors of post-fracture mortality were male gender (hazard ratio [HR] 2.4; 95% CI, 1.79–3.21), advancing age (HR 1.67; 1.53–1.83), and lower femoral neck BMD (HR 1.16; 1.01–1.33). A 70-year-old man with a fracture is predicted to have a skeletal age of 75. These results were incorporated into a prediction model to aid patient-doctor discussion about fracture vulnerability and treatment decisions

External validation of the Garvan nomograms for predicting absolute fracture risk: The Tromso study

Background: Absolute risk estimation is a preferred approach for assessing fracture risk and treatment decision making. This study aimed to evaluate and validate the predictive performance of the Garvan Fracture Risk Calculator in a Norwegian cohort. Methods: The analysis included 1637 women and 1355 aged 60+ years from the Tromsø study. All incident fragility fractures between 2001 and 2009 were registered. The predicted probabilities of non-vertebral osteoporotic and hip fractures were determined using models with and without BMD. The discrimination and calibration of the models were assessed.Reclassification analysis was used to compare the models performance. Results: The incidence of osteoporotic and hip fracture was 31.5 and 8.6 per 1000 population in women, respectively; in men the corresponding incidence was 12.2 and 5.1. The predicted 5-year and 10-year probability of fractures was consistently higher in the fracture group than the non-fracture group for all models. The 10-year predicted probabilities of hip fracture in those with fracture was 2.8 (women) to 3.1 times (men) higher than those without fracture. There was a close agreement between predicted and observed risk in both sexes and up to the fifth quintile. Among those in the highest quintile of risk, the models over-estimated the risk of fracture. Models with BMD performed better than models with body weight in correct classification of risk in individuals with and without fracture. The overall net decrease in reclassification of the model with weight compared to the model with BMD was 10.6% (p = 0.008) in women and 17.2% (p = 0.001) in men for osteoporotic fractures, and 13.3% (p = 0.07) in women and 17.5% (p = 0.09) in men for hip fracture. Conclusions: The Garvan Fracture Risk Calculator is valid and clinically useful in identifying individuals at high risk of fracture. The models with BMD performed better than those with body weight in fracture risk prediction

Capture the fracture: a best practice framework and global campaign to break the fragility fracture cycle

Summary The International Osteoporosis Foundation (IOF) Capture the Fracture Campaign aims to support implementation of Fracture Liaison Services (FLS) throughout the world. Introduction FLS have been shown to close the ubiquitous secondary fracture prevention care gap, ensuring that fragility fracture sufferers receive appropriate assessment and intervention to reduce future fracture risk. Methods Capture the Fracture has developed internationally endorsed standards for best practice, will facilitate change at the national level to drive adoption of FLS and increase awareness of the challenges and opportunities presented by secondary fracture prevention to key stakeholders. The Best Practice Framework (BPF) sets an international benchmark for FLS, which defines essential and aspirational elements of service delivery. Results The BPF has been reviewed by leading experts from many countries and subject to beta-testing to ensure that it is internationally relevant and fit-for-purpose. The BPF will also serve as a measurement tool for IOF to award ‘Capture the Fracture Best Practice Recognition’ to celebrate successful FLS worldwide and drive service development in areas of unmet need. The Capture the Fracture website will provide a suite of resources related to FLS and secondary fracture prevention, which will be updated as new materials become available. A mentoring programme will enable those in the early stages of development of FLS to learn from colleagues elsewhere that have achieved Best Practice Recognition. A grant programme is in development to aid clinical systems which require financial assistance to establish FLS in their localities. Conclusion Nearly half a billion people will reach retirement age during the next 20 years. IOF has developed Capture the Fracture because this is the single most important thing that can be done to directly improve patient care, of both women and men, and reduce the spiralling fracture-related care costs worldwide.</p