Summary
The introduction of the WHO FRAX® algorithms has facilitated the assessment of fracture risk on the basis of fracture probability. Its use in fracture risk prediction has strengths, but also ...limitations of which the clinician should be aware and are the focus of this review
Introduction
The International Osteoporosis Foundation (IOF) and the International Society for Clinical Densitometry (ISCD) appointed a joint Task Force to develop resource documents in order to make recommendations on how to improve FRAX and better inform clinicians who use FRAX. The Task Force met in November 2010 for 3 days to discuss these topics which form the focus of this review.
Methods
This study reviews the resource documents and joint position statements of ISCD and IOF.
Results
Details on the clinical risk factors currently used in FRAX are provided, and the reasons for the exclusion of others are provided. Recommendations are made for the development of surrogate models where country-specific FRAX models are not available.
Conclusions
The wish list of clinicians for the modulation of FRAX is large, but in many instances, these wishes cannot presently be fulfilled; however, an explanation and understanding of the reasons may be helpful in translating the information provided by FRAX into clinical practice.
Abstract Trabecular bone score (TBS) is a texture index derived from standard lumbar spine dual energy X-ray absorptiometry (DXA) images and provides information about the underlying bone independent ...of the bone mineral density (BMD). Several salient observations have emerged. Numerous studies have examined the relationship between TBS and fracture risk and have shown that lower TBS values are associated with increased risk for major osteoporotic fracture in postmenopausal women and older men, with this result being independent of BMD values and other clinical risk factors. Therefore, despite being derived from standard DXA images, the information contained in TBS is independent and complementary to the information provided by BMD and the FRAX® tool. A procedure to generate TBS-adjusted FRAX probabilities has become available with the resultant predicted fracture risks shown to be more accurate than the standard FRAX tool. With these developments, TBS has emerged as a clinical tool for improved fracture risk prediction and guiding decisions regarding treatment initiation, particularly for patients with FRAX probabilities around an intervention threshold. In this article, we review the development, validation, clinical application, and limitations of TBS.
Transgenic maize engineered to express insecticidal proteins from the bacterium Bacillus thuringiensis (Bt) has become widely adopted in U.S. agriculture. In 2009, Bt maize was planted on more than ...22.2 million hectares, constituting 63% of the U.S. crop. Using statistical analysis of per capita growth rate estimates, we found that areawide suppression of the primary pest Ostrinia nubilalis (European corn borer) is associated with Bt maize use. Cumulative benefits over 14 years are an estimated $3.2 billion for maize growers in Illinois, Minnesota, and Wisconsin, with more than $2.4 billion of this total accruing to non-Bt maize growers. Comparable estimates for Iowa and Nebraska are $3.6 billion in total, with $1.9 billion for non-Bt maize growers. These results affirm theoretical predictions of pest population suppression and highlight economic incentives for growers to maintain non-Bt maize refugia for sustainable insect resistance management.
Fragility fractures are increasingly recognized as a complication of both type 1 and type 2 diabetes, with fracture risk that increases with disease duration and poor glycemic control. Yet the ...identification and management of fracture risk in these patients remains challenging. This review explores the clinical characteristics of bone fragility in adults with diabetes and highlights recent studies that have evaluated bone mineral density (BMD), bone microstructure and material properties, biochemical markers, and fracture prediction algorithms (i.e., FRAX) in these patients. It further reviews the impact of diabetes drugs on bone as well as the efficacy of osteoporosis treatments in this population. We finally propose an algorithm for the identification and management of diabetic patients at increased fracture risk.
Summary A new Canadian WHO fracture risk assessment (FRAX®) tool to predict 10-year fracture probability was compared with observed 10-year fracture outcomes in a large Canadian population-based ...study (CaMos). The Canadian FRAX tool showed good calibration and discrimination for both hip and major osteoporotic fractures. Introduction The purpose of this study was to validate a new Canadian WHO fracture risk assessment (FRAX®) tool in a prospective, population-based cohort, the Canadian Multicentre Osteoporosis Study (CaMos). Methods A FRAX tool calibrated to the Canadian population was developed by the WHO Collaborating Centre for Metabolic Bone Diseases using national hip fracture and mortality data. Ten-year FRAX probabilities with and without bone mineral density (BMD) were derived for CaMos women (N = 4,778) and men (N = 1,919) and compared with observed fracture outcomes to 10 years (Kaplan-Meier method). Cox proportional hazard models were used to investigate the contribution of individual FRAX variables. Results Mean overall 10-year FRAX probability with BMD for major osteoporotic fractures was not significantly different from the observed value in men predicted 5.4% vs. observed 6.4% (95%CI 5.2-7.5%) and only slightly lower in women predicted 10.8% vs. observed 12.0% (95%CI 11.0-12.9%). FRAX was well calibrated for hip fracture assessment in women predicted 2.7% vs. observed 2.7% (95%CI 2.2-3.2%) but underestimated risk in men predicted 1.3% vs. observed 2.4% (95%CI 1.7-3.1%). FRAX with BMD showed better fracture discrimination than FRAX without BMD or BMD alone. Age, body mass index, prior fragility fracture and femoral neck BMD were significant independent predictors of major osteoporotic fractures; sex, age, prior fragility fracture and femoral neck BMD were significant independent predictors of hip fractures. Conclusion The Canadian FRAX tool provides predictions consistent with observed fracture rates in Canadian women and men, thereby providing a valuable tool for Canadian clinicians assessing patients at risk of fracture.
Summary
Non-traumatic fractures at typical osteoporotic sites are associated with increased mortality across all age groups, particularly in men. Furthermore, in certain age subgroups of women and ...men, this rate remained elevated beyond 5 years for fractures of the hip, vertebrae, humerus, and other sites.
Introduction
Increased mortality rates have been documented following non-traumatic hip, vertebral, and shoulder fractures. However, data are lacking as to the duration of excess mortality and whether there is increased mortality following fractures at other sites. We determined mortality up to 15 years following incident fractures at typical osteoporotic sites.
Methods
Using healthcare databases for the Province of Manitoba, Canada, we identified individuals 50 years and older with an incident non-traumatic fracture between 1986 and 2007. Each fracture case was matched to three fracture-free controls. Generalized linear models were used to test for trends in mortality and to estimate the relative risk for cases after adjusting for co-morbidity and living arrangements.
Results
During the study period, we identified 21,067 incident fractures in men followed by 10,724 (50.1%) deaths and 49,197 incident fractures in women followed by 22,018 deaths (44.8%). Seventy-six percent of the fractures were at sites other than the hip and vertebrae. After adjustment for age, number of co-morbidities, and level of dependence in living arrangements, the risk of death in cases, relative to controls, was increased in both sexes for hip, vertebral, humerus, wrist (in men only), and other fracture sites. Post-fracture mortality was higher in men than women. Relative mortality was the highest in the younger age groups across the spectrum of fracture sites.
Conclusions
Fractures at typical osteoporotic sites are associated with increased mortality across all age groups, particularly in men. Better understanding of factors associated with increased post-fracture mortality should inform the development of management strategies.
To determine prevalence of delirium in critically ill children and explore associated risk factors.
Multi-institutional point prevalence study.
Twenty-five pediatric critical care units in the United ...States, the Netherlands, New Zealand, Australia, and Saudi Arabia.
All children admitted to the pediatric critical care units on designated study days (n = 994).
Children were screened for delirium using the Cornell Assessment of Pediatric Delirium by the bedside nurse. Demographic and treatment-related variables were collected.
Primary study outcome measure was prevalence of delirium. In 159 children, a final determination of mental status could not be ascertained. Of the 835 remaining subjects, 25% screened positive for delirium, 13% were classified as comatose, and 62% were delirium-free and coma-free. Delirium prevalence rates varied significantly with reason for ICU admission, with highest delirium rates found in children admitted with an infectious or inflammatory disorder. For children who were in the PICU for 6 or more days, delirium prevalence rate was 38%. In a multivariate model, risk factors independently associated with development of delirium included age less than 2 years, mechanical ventilation, benzodiazepines, narcotics, use of physical restraints, and exposure to vasopressors and antiepileptics.
Delirium is a prevalent complication of critical illness in children, with identifiable risk factors. Further multi-institutional, longitudinal studies are required to investigate effect of delirium on long-term outcomes and possible preventive and treatment measures. Universal delirium screening is practical and can be implemented in pediatric critical care units.
Abstract Introduction One quarter of osteoporotic fractures occur in men. TBS, a gray-level measurement derived from lumbar spine DXA image texture, is related to microarchitecture and fracture risk ...independently of BMD. Previous studies reported the ability of spine TBS to predict osteoporotic fractures in women. Our aim was to evaluate the ability of TBS to predict clinical osteoporotic fractures in men. Methods 3620 men aged ≥ 50 (mean 67.6 years) at the time of baseline DXA (femoral neck, spine) were identified from a database (Province of Manitoba, Canada). Health service records were assessed for the presence of non-traumatic osteoporotic fracture after BMD testing. Lumbar spine TBS was derived from spine DXA blinded to clinical parameters and outcomes. We used Cox proportional hazard regression to analyze time to first fracture adjusted for clinical risk factors (FRAX without BMD), osteoporosis treatment and BMD (hip or spine). Results Mean followup was 4.5 years. 183 (5.1%) men sustain major osteoporotic fractures (MOF), 91 (2.5%) clinical vertebral fractures (CVF), and 46 (1.3%) hip fractures (HF). Correlation between spine BMD and spine TBS was modest (r = 0.31), less than correlation between spine and hip BMD (r = 0.63). Significantly lower spine TBS were found in fracture versus non-fracture men for MOF (p < 0.001), HF (p < 0.001) and CVF (p = 0.003). Area under the receiver operating characteristic curve (AUC) for incident fracture discrimination with TBS was significantly better than chance (MOF AUC = 0.59, p < 0.001; HF AUC = 0.67, p < 0.001; CVF AUC = 0.57, p = 0.032). TBS predicted MOF and HF (but not CVF) in models adjusted for FRAX without BMD and osteoporosis treatment. TBS remained a predictor of HF (but not MOF) after further adjustment for hip BMD or spine BMD. Conclusion We observed that spine TBS predicted MOF and HF independently of the clinical FRAX score, HF independently of FRAX and BMD in men. Studies with more incident fractures are needed to confirm these findings.
Competing interests: All authors received consulting fees and travel support from Osteoporosis Canada during the preparation of this article. In addition, Alexandra Papaioannou MD MSc has been an ...advisory board member for Amgen, Eli Lilly, Merck Frosst, Novartis and Procter & Gamble; has served as a consult - ant to Amgen, Aventis Pharma, Eli Lilly, Lundbeck Canada Inc., Merck Frosst, Novartis, Procter & Gamble, Servier, Warner Chillcott and WyethosteoAyerst; has received unrestricted research grants from Amgen, Eli Lilly, Merck Frosst, Procter & Gamble and Sanofi-Aventis; has received clinical trial grants from Novartis and Pfizer; has received a research grant from the Ontario Ministry of Health and Long-Term Care; and has served as a member of the Continuing Medical Education Steering Committee of the Ontario College of Family Physicians. Suzanne Morin has been an advisory board member for Amgen, Eli Lilly, Novartis and Warner-Chilcott and has received speaker's honoraria from Amgen, Novartis and Merck. Angela M. Cheung has been an advisory board member for Amgen and Eli Lilly; has served as a consultant for Merck; and has received speaker's honoraria from Amgen, Eli Lilly, Merck, Novartis and Warner Chilcott. Stephanie Atkinson PhD has served as a consultant to Pfizer and Wyeth Nutritionals and has participated in a multisite clinical trial funded by Novartis. Jacques P. Brown MD has been an advisory board member for Amgen, Eli Lilly, Merck, Novartis and Warner Chilcott; has served as a consultant for Amgen, Eli Lilly, Merck, Novartis and Warner Chilcott; has received grants from Abbott, Amgen, Eli Lilly, GlaxoSmithKline, Merck, Novartis, Pfizer, Roche, Sanofi-Aventis, Servier and Warner Chilcott; and has received speaker's honoraria from Amgen, Eli Lilly, Merck, Novartis and Warner Chilcott. David A. Hanley MD has served as an advisory board member for Amgen Canada, Eli Lilly Canada, Novartis Canada, NPS Pharmaceuticals, Servier Canada and Warner Chilcott; has participated in clinical trials funded by Amgen, Eli Lilly, Novartis, NPS Pharmaceuticals, Pfizer, Servier and Wyeth Ayerst; and has received speaker's honor aria from Amgen Canada, Eli Lilly Canada, Novartis Canada, NPS Pharmaceuticals and Servier Canada. Anthony Hodsman has been an advis - ory board member for Amgen Canada, Novartis Canada, Procter & Gamble Canada, Shire Pharmaceuticals Canada and Warner-Chilcott Canada; has served as a consultant to Cytochroma Canada; and has received speaker's honoraria from McGill University and Novartis Canada. Stephanie M. Kaiser MD has served as an advisory board member for Amgen, AstaZeneca, Bristol Myers Squibb, Eli Lilly Canada, Merck Frosst/Schering, Novartis and Servier; has received speaker's honoraria from Amgen, AstraZeneca, Eli Lilly, Merck Frosst/Schering Plough, Novartis, Procter and Gamble (now Warner Chilcott/Aventis), and Servier Canada; has received payment for development of educational presentations from Eli Lilly Canada Inc.; and has received travel funds for activities unrelated to this paper from Amgen Canada. Brent Kvern has been an advisory board member for the Alliance for Better Bone Health (sponsored by SanofiAventis and Warner) and for Amgen Canada; has served as a consultant for Servier Canada; has received honoraria from the Alliance for Better Bone Health, Amgen Canada, Eli Lilly, Merck Frosst Canada and Servier Canada; and has received payment for development of educational presentations from the Alliance for Better Bone Health, Amgen Canada, Eli Lilly, Merck Frosst Canada and Servier Canada. William D. Leslie MD MSc has been an advisory board member for Amgen, Genzyme and Novartis; has received unrestricted research grants from Amgen, Genzyme, Merck Frosst, Procter & Gamble and Sanofi-Aventis; has received speaker's fees from Amgen and Merck Frosst; and has received travel funds for activities unrelated to this paper from Genzyme. No additional competing interests declared for Sidney Feldman, Sophie A. Jamal MD PhD and Kerry Siminoski MD.
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