Race-specific FRAX models are evidence-based and support equitable care: a response to the ASBMR Task Force report on Clinical Algorithms for Fracture Risk.

Task Force on 'Clinical Algorithms for Fracture Risk' commissioned by the American Society for Bone and Mineral Research (ASBMR) Professional Practice Committee has recommended that FRAX® models in the US do not include adjustment for race and ethnicity. This position paper finds that an agnostic model would unfairly discriminate against the Black, Asian and Hispanic communities and recommends the retention of ethnic and race-specific FRAX models for the US, preferably with updated data on fracture and death hazards. In contrast, the use of intervention thresholds based on a fixed bone mineral density unfairly discriminates against the Black, Asian and Hispanic communities in the US. This position of the Working Group on Epidemiology and Quality of Life of the International Osteoporosis Foundation (IOF) is endorsed both by the IOF and the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO).

Long-term and sequential treatment for osteoporosis.

Osteoporosis is a skeletal disorder that causes impairment of bone structure and strength, leading to a progressively increased risk of fragility fractures. The global prevalence of osteoporosis is increasing in the ageing population. Owing to the chronic character of osteoporosis, years or even decades of preventive measures or therapy are required. The long-term use of bone-specific pharmacological treatment options, including antiresorptive and/or osteoanabolic approaches, has raised concerns around adverse effects or potential rebound phenomena after treatment discontinuation. Imaging options, risk scores and the assessment of bone turnover during initiation and monitoring of such therapies could help to inform individualized treatment strategies. Combination therapies are currently used less often than 'sequential' treatments. However, all patients with osteoporosis, including those with secondary and rare causes of osteoporosis, as well as specific patient populations (for example, young adults, men and pregnant women) require new approaches for long-term therapy and disease monitoring. New pathophysiological aspects of bone metabolism might therefore help to inform and revolutionize the diagnosis and treatment of osteoporosis.

Osteoporosis treatment in Austria-assessment of FRAX-based intervention thresholds for high and very high fracture risk.

The adoption of the management pathway proposed by the National Osteoporosis Guideline Group (NOGG), UK applied using the Austrian FRAX® tool in a referral population of Austrian women categorises 22-29% of women age 40 years or more eligible for treatment of whom 28-34% are classified at very high risk. PURPOSE: The aim of this study is to provide a reference document for the further development of existing guidelines for the management of osteoporosis in Austria, considering FRAX-based intervention thresholds for high and very high fracture risk. METHODS: The model development was based on two Austrian hospital referral cohorts. Baseline information was collected to compute the 10-year probability (using the Austrian FRAX model) of a major osteoporotic fracture (MOF) and hip fracture both with and without the inclusion of femoral neck bone mineral density (BMD). Assessment thresholds for BMD testing were defined, as well as intervention thresholds. In addition, thresholds that characterise men and women at high and very high fracture risk were established. The management pathway followed that currently recommended by the UK National Osteoporosis Guideline Group (NOGG). RESULTS: The two cohorts comprised a total of 1306 women and men with a mean age of 66.7 years. Slightly more than 50% were eligible for treatment by virtue of a prior fragility fracture. In those women without a prior fracture, 22% (n = 120) were eligible for treatment based on MOF probabilities. Of these, 28% (n = 33) were found to be at very high risk. When both MOF and hip fracture probabilities were used to characterise risk, 164 women without a prior fracture were eligible for treatment (29%). Of these, 34% (n = 56) were found to be at very high risk. Fewer men without prior fracture were eligible for treatment compared with women. CONCLUSION: The management pathway as currently outlined is expected to reduce inequalities in patient management. The characterisation of very high risk may aid in the identification of patients suitable for treatment with osteoanabolic agents.

Osteoporosis and Fragility Fractures: currently available pharmacological options and future directions.

Osteoporosis is a systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture. The average lifetime risk of a 50-year-old woman to suffer a fracture of the spine, hip, proximal humerus, or distal forearm has been estimated at close to 50%. In general, pharmacological treatment is recommended in patients who suffered a fragility fracture because their risk of suffering a subsequent fracture is increased dramatically. Therefore, many guidelines recommend pharmacological treatment in patients without a prevalent fracture if their fracture probability is comparable to or higher than that of a person of the same age with a prevalent fracture. The present review aims to highlight currently available pharmacological treatment options and their antifracture efficacy including safety aspects. Drug classes discussed comprise bisphosphonates, selective estrogen receptor modulators, parathyroid hormone peptides and derivatives, humanized monoclonal antibodies, and estrogens and gestagens and their combinations. Furthermore, a brief glimpse is provided into a potentially promising treatment option that involves mesenchymal stem cells.

Automated Knee Osteoarthritis Assessment Increases Physicians' Agreement Rate and Accuracy: Data from the Osteoarthritis Initiative.

Objective. To assess the impact of a computerized system on physicians' accuracy and agreement rate, as compared with unaided diagnosis. Methods. A set of 124 unilateral knee radiographs from the Osteoarthritis Initiative (OAI) study were analyzed by a computerized method with regard to Kellgren-Lawrence (KL) grade, as well as joint space narrowing, osteophytes, and sclerosis Osteoarthritis Research Society International (OARSI) grades. Physicians scored all images, with regard to osteophytes, sclerosis, joint space narrowing OARSI grades and KL grade, in 2 modalities: through a plain radiograph (unaided) and a radiograph presented together with the report from the computer assisted detection system (aided). Intraclass correlation between the physicians was calculated for both modalities. Furthermore, physicians' performance was compared with the grading of the OAI study, and accuracy, sensitivity, and specificity were calculated in both modalities for each of the scored features. Results. Agreement rates for KL grade, sclerosis, and osteophyte OARSI grades, were statistically increased in the aided versus the unaided modality. Readings for joint space narrowing OARSI grade did not show a statistically difference between the 2 modalities. Readers' accuracy and specificity for KL grade >0, KL >1, sclerosis OARSI grade >0, and osteophyte OARSI grade >0 was significantly increased in the aided modality. Reader sensitivity was high in both modalities. Conclusions. These results show that the use of an automated knee OA software increases consistency between physicians when grading radiographic features of OA. The use of the software also increased accuracy measures as compared with the OAI study, mostly through increases in specificity.

Effect of eplerenone on markers of bone turnover in patients with primary hyperparathyroidism - The randomized, placebo-controlled EPATH trial.

Mineralocorticoid receptor (MR) antagonism may affect bone turnover via direct and indirect pathways involving parathyroid hormone, but randomized controlled trials are lacking. In a pre-specified analysis of the "Eplerenone in primary hyperparathyroidism" placebo-controlled, randomized trial (ISRCTN 33941607), effects of eight weeks MR-blockade with eplerenone on bone turnover markers in 97 patients with primary hyperparathyroidism were tested. Mean age was 67.5±9.5years, and 76 (78.4%) were females. In analysis of covariance with adjustment for baseline values, eplerenone had no significant effect on isoform 5b of the tartrate-resistant acid phosphatase (TRAP), beta-crosslaps, N-terminal propeptide of procollagen type 1 (P1NP), osteocalcin and bone-specific alkaline phosphatase. There was no significant cross-sectional correlation between plasma aldosterone concentration or the aldosterone-to-renin ratio and markers of bone turnover in multivariate linear regression models at baseline. These data provide first evidence from a randomized and placebo-controlled trial that short-term MR antagonism may not affect bone turnover, at least in patients with primary hyperparathyroidism.

Plasma parathyroid hormone and cardiovascular disease in treatment-naive patients with primary hyperparathyroidism: The EPATH trial.

Patients with primary hyperparathyroidism are at increased risk for high blood pressure, vascular stiffening, and left ventricular hypertrophy, but previous studies have failed to demonstrate the direct associations with circulating parathyroid hormone (PTH) levels. The authors investigated cross-sectional relationships between PTH and 24-hour pulse wave velocity, nocturnal systolic blood pressure, and left ventricular mass index in patients with primary hyperparathyroidism who were treatment-naive with cinacalcet, renin-angiotensin-aldosterone-system inhibitors, and thiazide or loop diuretics. In 76 patients, mean±SD of pulse wave velocity, nocturnal systolic blood pressure, and left ventricular mass index values were 9.3±1.8 m/s, 116.6±17.0 mm Hg, and 92.8±23.0 g/m². In multivariate linear regression analyses with adjustment for potentially confounding parameters, PTH was independently associated with nocturnal systolic blood pressure (adjusted ß coefficient=.284, P=.040), mean 24-hour pulse wave velocity (ß=.199, P=.001), and left ventricular mass index (ß=.252, P=.025). PTH may promote vascular and cardiac remodeling in primary hyperparathyroidism. Interventional trials are needed to test the antihypertensive and cardioprotective effects of PTH-inhibitory treatment strategies.

Use of dual-energy X-ray absorptiometry (DXA) for diagnosis and fracture risk assessment; WHO-criteria, T- and Z-score, and reference databases.

Dual-energy X-ray absorptiometry (DXA) is a two-dimensional imaging technology developed to assess bone mineral density (BMD) of the entire human skeleton and also specifically of skeletal sites known to be most vulnerable to fracture. In order to simplify interpretation of BMD measurement results and allow comparability among different DXA-devices, the T-score concept was introduced. This concept involves an individual's BMD which is then compared with the mean value of a young healthy reference population, with the difference expressed as a standard deviation (SD). Since the early nineties of the past century, the diagnostic categories "normal, osteopenia, and osteoporosis", as recommended by a WHO working Group, are based on this concept. Thus, DXA is still the globally accepted "gold-standard" method for the noninvasive diagnosis of osteoporosis. Another score obtained from DXA measurement, termed Z-score, describes the number of SDs by which the BMD in an individual differs from the mean value expected for age and sex. Although not intended for diagnosis of osteoporosis in adults, it nevertheless provides information about an individual's fracture risk compared to peers. DXA measurement can either be used as a "stand-alone" means in the assessment of an individual's fracture risk, or incorporated into one of the available fracture risk assessment tools such as FRAX® or Garvan, thus improving the predictive power of such tools. The issue which reference databases should be used by DXA-device manufacturers for T-score reference standards has been recently addressed by an expert group, who recommended use National Health and Nutrition Examination Survey III (NHANES III) databases for the hip reference standard but own databases for the lumbar spine. Furthermore, in men it is recommended use female reference databases for calculation of the T-score and use male reference databases for calculation of Z-score.

Medical University admission test: a confirmatory factor analysis of the results.

BACKGROUND: The Graz Admission Test has been applied since the academic year 2006/2007. The validity of the Test was demonstrated by a significant improvement of study success and a significant reduction of dropout rate. The purpose of this study was a detailed analysis of the internal correlation structure of the various components of the Graz Admission Test. In particular, the question investigated was whether or not the various test parts constitute a suitable construct which might be designated as "Basic Knowledge in Natural Science." METHODS: This study is an observational investigation, analyzing the results of the Graz Admission Test for the study of human medicine and dentistry. A total of 4741 applicants were included in the analysis. Principal component factor analysis (PCFA) as well as techniques from structural equation modeling, specifically confirmatory factor analysis (CFA), were employed to detect potential underlying latent variables governing the behavior of the measured variables. RESULTS: PCFA showed good clustering of the science test parts, including also text comprehension. A putative latent variable "Basic Knowledge in Natural Science," investigated by CFA, was indeed shown to govern the response behavior of the applicants in biology, chemistry, physics, and mathematics as well as text comprehension. The analysis of the correlation structure of the various test parts confirmed that the science test parts together with text comprehension constitute a satisfactory instrument for measuring a latent construct variable "Basic Knowledge in Natural Science." CONCLUSIONS: The present results suggest the fundamental importance of basic science knowledge for results obtained in the framework of the admission process for medical universities.

Situational judgment test as an additional tool in a medical admission test: an observational investigation.

BACKGROUND: In the framework of medical university admission procedures the assessment of non-cognitive abilities is increasingly demanded. As tool for assessing personal qualities or the ability to handle theoretical social constructs in complex situations, the Situational Judgment Test (SJT), among other measurement instruments, is discussed in the literature. This study focuses on the development and the results of the SJT as part of the admission test for the study of human medicine and dentistry at one medical university in Austria. METHODS: Observational investigation focusing on the results of the SJT. 4741 applicants were included in the study. To yield comparable results for the different test parts, "relative scores" for each test part were calculated. Performance differences between women and men in the various test parts are analyzed using effect sizes based on comparison of mean values (Cohen's d). The associations between the relative scores achieved in the various test parts were assessed by computing pairwise linear correlation coefficients between all test parts and visualized by bivariate scatterplots. RESULTS: Among successful candidates, men consistently outperform women. Men perform better in physics and mathematics. Women perform better in the SJT part. The least discriminatory test part was the SJT. A strong correlation between biology and chemistry and moderate correlations between the other test parts except SJT is obvious. The relative scores are not symmetrically distributed. CONCLUSIONS: The cognitive loading of the performed SJTs points to the low correlation between the SJTs and cognitive abilities. Adding the SJT part into the admission test, in order to cover more than only knowledge and understanding of natural sciences among the applicants has been quite successful.

Have "new" methods in medical education reached German-speaking Central Europe: a survey.

BACKGROUND: Simulation-based-training (SBT) in the education of health professionals is discussed as an effective alternative for knowledge and skills enhancement as well as for the establishment of a secure learning environment, for learners and patients. In the Anglo-American region, SBT and simulation and training centers (STC) are numbered as standard for medical training. In German-speaking Central Europe, priority is still given to the establishment of SBT and STC. The purpose of this study was (i) to survey the status quo relating to the existence and facilities of simulation and training centers at medical universities in German-speaking Central Europe and (ii) the evaluation of training methods, especially in the area of emergency medicine skills. METHODS: All public and private medical universities or medical faculties in Germany (36), Austria (4) and German-speaking Switzerland (3) were interviewed. In the survey, information regarding the existence and facilities of STCs and information with regards to the use of SBT in the area of emergency medicine was requested. The questions were partly posed in a closed-ended-, in an open-ended- and in a multiple choice format (with the possibility of selecting more than one answer). RESULTS: Of a total of 43 contacted medical universities/medical faculties, 40 ultimately participated in the survey. As decisive for the establishment of a STC the potential to improve the clinical-practical training and the demand by students were listed. Obligatory training in a STC during the first and sixth academic year was confirmed only by 12 institutions, before the first invasive procedure on patients by 17 institutions. 13 institutions confirmed the use of the STC for the further training of physicians and care-staff. Training for the acute care and emergency medicine skills in the field of pediatrics, for the most part, occurs decentralized. CONCLUSIONS: New methods in medical training have reached German-speaking Central Europe, but the simulation and training centers vary in size, equipment or regarding their integration into the obligatory curriculum as much as the number and variety of the offering to be trained voluntarily or on an obligatory basis.

Clinicians should be aware of their responsibilities as role models: a case report on the impact of poor role modeling.

BACKGROUND: Role modeling is an important and valuable educational method. It is predominant throughout (under-)graduate medical education, and attributes of exemplary medical role models are manifold. AIM: This article describes the impact of poor role modeling on medical students' professional and personal development on the basis of a singular incident at an associated teaching hospital. In addition, scientific literature studying the effect of and the reasons behind poor role modeling in undergraduate and graduate medical education is analyzed and discussed. RESULTS: To maximize the educational potential of clinical role modeling, medical schools have to consider strategies both on the individual as well as on the institutional level. Several suggestions are offered on both levels. DISCUSSION/CONCLUSION: Based on a case report of significantly poor role modeling, this article outlines strategies through which academic medical institutions may maximize the educational potential of role modeling and lastingly enhance teaching proficiency of clinical faculty.

Official Positions for FRAX® clinical regarding smoking from Joint Official Positions Development Conference of the International Society for Clinical Densitometry and International Osteoporosis Foundation on FRAX®.

The worldwide prevalence of smoking has been estimated at about 50% in men, and 10% in women, with larger variations among different populations studied. Smoking has been shown to affect many organ systems resulting in severe morbidity and increased mortality. In addition, smoking has been identified as a predictor of ten-year fracture risk in men and women, largely independent of an individual's bone mineral density. This finding has eventually lead to incorporation of this risk factor into FRAX®, an algorithm that has been developed to calculate an individual's ten-year fracture risk. However, only little, or conflicting data is available on a possible association between smoking dose, duration, length of time after cessation, type of tobacco and fracture risk, limiting this risk factor's applicability in the context of FRAX®.

New considerations on the management of osteoporosis in Central and Eastern Europe (CEE): summary of the "3rd Summit on Osteoporosis-CEE", November 2009, Budapest, Hungary.

INTRODUCTION: In November 2009, the "3rd Summit on Osteoporosis-Central and Eastern Europe (CEE)" was held in Budapest, Hungary. The conference aimed to tackle issues regarding osteoporosis management in CEE identified during the second CEE summit in 2008 and to agree on approaches that allow most efficient and cost-effective diagnosis and therapy of osteoporosis in CEE countries in the future. DISCUSSION: The following topics were covered: past year experience from FRAX® implementation into local diagnostic algorithms; causes of secondary osteoporosis as a FRAX® risk factor; bone turnover markers to estimate bone loss, fracture risk, or monitor therapies; role of quantitative ultrasound in osteoporosis management; compliance and economical aspects of osteoporosis; and osteoporosis and genetics. Consensus and recommendations developed on these topics are summarised in the present progress report. CONCLUSION: Lectures on up-to-date data of topical interest, the distinct regional provenances of the participants, a special focus on practical aspects, intense mutual exchange of individual experiences, strong interest in cross-border cooperations, as well as the readiness to learn from each other considerably contributed to the establishment of these recommendations. The "4th Summit on Osteoporosis-CEE" held in Prague, Czech Republic, in December 2010 will reveal whether these recommendations prove of value when implemented in the clinical routine or whether further improvements are still required.

Vitamin D status and its relationship with bone mineral density and parathyroid hormone in Southeast Asian adults with low bone density.

OBJECTIVE: To investigate the vitamin D sufficiency status and the relationships among serum 25-hydroxyvitamin D [25(OH)D] levels, intact parathyroid hormone (iPTH) levels, and bone mineral density (BMD) in patients attending an osteoporosis clinic in Singapore. METHODS: In total, 193 adults with or without prevalent fragility fractures and with low BMD at the femoral neck, total hip, or lumbar spine underwent assessment. Multivariate regression models were used to investigate the relationships among serum 25(OH)D, iPTH, and BMD. RESULTS: The mean values (standard deviation) for age of the patients and serum 25(OH)D level were 61 (14) years and 26.05 (7.97) ng/mL, respectively. In 72% of patients, serum 25(OH)D levels were below 30 ng/mL. There was no association between 25(OH)D levels and BMD at the femoral neck, total hip, or lumbar spine (P = .568, .461, and .312, respectively). Serum iPTH levels were negatively associated with BMD at the total hip (P = .035) and the lumbar spine (P = .019). At levels <30 ng/mL, 25(OH)D was negatively associated with iPTH (P = .036). CONCLUSION: Among this Southeast Asian population of patients with low BMD, no direct relationship between serum 25(OH)D levels and BMD was observed. A negative correlation existed, however, between iPTH and 25(OH)D at serum 25(OH)D concentrations <30 ng/mL, and serum iPTH levels showed a significant negative association with BMD at the total hip and lumbar spine. These significant negative associations between iPTH levels and BMD at the total hip and lumbar spine underscore the critical role of this hormone in bone metabolism and health.

Association of vitamin D deficiency with heart failure and sudden cardiac death in a large cross-sectional study of patients referred for coronary angiography.

CONTEXT: Vitamin D has been shown to influence cardiac contractility and myocardial calcium homeostasis. OBJECTIVES: We aimed to elucidate whether insufficient vitamin D status is associated with heart failure and sudden cardiac death (SCD). DESIGN, SETTING, AND PARTICIPANTS: We measured 25-hydroxyvitamin D [25(OH)D] levels in 3299 Caucasian patients who were routinely referred to coronary angiography at baseline (1997-2000). MAIN OUTCOME MEASURES: The main outcome was cross-sectional associations of 25(OH)D levels with measures of heart failure and Cox proportional hazard ratios for deaths due to heart failure and for SCD according to vitamin D status. RESULTS: 25(OH)D was negatively correlated with N-terminal pro-B-type natriuretic peptide and was inversely associated with higher New York Heart Association classes and impaired left ventricular function. During a median follow-up time of 7.7 yr, 116 patients died due to heart failure and 188 due to SCD. After adjustment for cardiovascular risk factors, the hazard ratios (with 95% confidence intervals) for death due to heart failure and for SCD were 2.84 (1.20-6.74) and 5.05 (2.13-11.97), respectively, when comparing patients with severe vitamin D deficiency [25(OH)D <25 nmol/liter)] with persons in the optimal range [25(OH)D > or =75 nmol/liter]. In all statistical analyses, we obtained similar results with 25(OH)D and with 1,25-dihydroxyvitamin D. CONCLUSIONS: Low levels of 25(OH)D and 1,25-dihydroxyvitamin D are associated with prevalent myocardial dysfunction, deaths due to heart failure, and SCD. Interventional trials are warranted to elucidate whether vitamin D supplementation is useful for treatment and/or prevention of myocardial diseases.