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Abstract: Tools to predict fracture risk are useful for selecting patients for pharmacological therapy in order to reduce fracture risk and redirect limited healthcare resources to those who are most likely to benefit. FRAX® is a World Health Organization fracture risk assessment algorithm for estimating the 10-year probability of hip fracture and major osteoporotic fracture. Effective application of FRAX® in clinical practice requires a thorough understanding of its limitations as well as its utility. For some patients, FRAX® may underestimate or overestimate fracture risk. In order to address some of the common issues encountered with the use of FRAX® for individual patients, the International Society for Clinical Densitometry (ISCD) and International Osteoporosis Foundation (IOF) assigned task forces to review the medical evidence and make recommendations for optimal use of FRAX® in clinical practice. Among the issues addressed were the use of bone mineral density (BMD) measurements at skeletal sites other than the femoral neck, the use of technologies other than dual-energy X-ray absorptiometry, the use of FRAX® without BMD input, the use of FRAX® to monitor treatment, and the addition of the rate of bone loss as a clinical risk factor for FRAX®. The evidence and recommendations were presented to a panel of experts at the Joint ISCD-IOF FRAX® Position Development Conference, resulting in the development of Joint ISCD-IOF Official Positions addressing FRAX®-related issues. [Copyright &y& Elsevier]

Abstract: A large body of epidemiological evidence suggests an inverse relationship between physical activity and risk of fractures. However, it is unclear how this association varies according to the domain of life in which the activity is undertaken. In this analysis of the European Prospective Investigation of Cancer-Norfolk study, we assessed total and domain-specific physical activity using a validated questionnaire (EPAQ2) in 14,903 participants (6514 men, mean age 62year) who also underwent quantitative ultrasound of the heel. After a median follow-up of 7.5years, there were 504 fractures of which 164 were hip fractures. In multivariable linear regression analysis, broadband ultrasound attenuation (BUA) was positively associated with total and leisure-time activities while showing no association with transportation and work activities. Home activities were associated with a lower BUA among younger participants. In multivariable Cox proportional-hazards models, moderate activities at home and in leisure time were associated with lower hip fracture risk among women (hazard ratios [HR] 0.51 and 0.55, p value 0.02 and 0.03, respectively). Among men, leisure-time activities were associated with lower risk of hip fracture (HR=0.58; p for trend<0.001) whereas activities at home were associated with higher risk of any fracture (HR=1.25; p for trend=0.008). Walking for leisure or transport was associated with lower risk of fracture in both men and women. Multivariable fractional polynomial modelling showed a U-shaped association between home activities and fracture risk especially among women. This study suggests that different domains of physical activity may relate differently to fracture risk and these relationships may vary by sex. [ABSTRACT FROM AUTHOR]

Abstract: The role of quantitative ultrasound (QUS) in clinical practice is debatable. An unanswered question is that whether combining QUS and BMD measurements could improve the prediction of fracture risk. We examined this in a sample of men and women in the European Prospective Investigation into Cancer (EPIC)-Norfolk who had both heel QUS and hip DXA between 1995 and 1997 and were followed for any incident fracture up to 2007. From 1455 participants (703 men) aged 65–76 years at baseline, 79 developed a fracture over 10.3±1.4 years of follow-up. Two separate sex-stratified Cox proportional-hazard models were used including clinical risk factors and total hip BMD. Heel broadband ultrasound attenuation (BUA) was also included in the second model. Global measures of model fit, area under ROC curve, and the Hosmer–Lemeshow statistic showed relative superiority of the model including BUA. Using each model, we calculated 10-year absolute risk of fracture for all participants and categorized them in groups of <5%, 5% to <15%, and ≥15%. Comparison of groupings showed a total re-classification of 16.6% of participants after inclusion of BUA with the greatest re-classification (30.7%) among the group with intermediate risk. Adding a QUS measurement to models based on clinical risk factors and BMD improves the predictive power of models and suggests that further attention should be paid to QUS as a clinical tool for fracture risk assessment. [Copyright &y& Elsevier]

Purpose: Physical activity helps maintain mobility, physical functioning, bone mineral density (BMD), muscle strength, balance and, therefore, may help prevent falls and fractures among the elderly. Meanwhile, it is theoretically possible that physical activity increases risk of fractures as it may increase risk of falls and has only a modest effect on BMD. This review aims to assess the potential causal association between physical activity and osteoporotic fractures from an epidemiological viewpoint. Methods: As the medical literature lacks direct evidence from randomized controlled trials (RCTs) with fracture end points, a meta-analysis of 13 prospective cohort studies with hip fracture end point is presented. The current evidence base regarding the link between exercise and fracture risk determinants (namely, falls, BMD, and bone quality) are also summarized. Results: Moderate-to-vigorous physical activity is associated with a hip fracture risk reduction of 45% (95% CI, 31-56%) and 38% (95% CI, 31-44%), respectively, among men and women. Risk of falling is suggested to be generally reduced among physically active people with a potential increased risk in the most active and inactive people. Positive effects of physical activity on BMD and bone quality are of a questionable magnitude for reduction of fracture risk. Conclusion: The complexity of relationship between physical activity and osteoporotic fractures points out to the need for RCTs to be conducted with fractures as the primary end point. [Copyright &y& Elsevier]

Abstract: A sample size of 30 degrees of freedom (df) for bone mineral density (BMD) precision studies may be insufficient for reliably categorizing change. Monte Carlo simulation was used to evaluate the effect of precision study sample size on identifying change in clinical patients. Least significant change (LSC) from 198 spine and 193 total hip scan-pairs was used to categorize change for 1420 patients undergoing BMD monitoring. Relative to this reference change fraction (RCF), LSC limits were identified that gave specified deviations from the RCF (−25% to +25%). Confidence limits (95% and 80%) for these LSC values (5 to 500 df) were estimated using ‘bootstrap’ samplings. A sample size providing 140 df is needed to avoid overdetecting spine change by 5% and 150 df to avoid underdetecting spine change by 5% with 95% confidence limits. A sample size of 30 df resulted in up to a 12.5% overdetection and 10.0% underdetection of spine or hip change based upon 95% confidence limits. In conclusion, assessing the effect of precision study sample size on classifying change in monitored patients is an important element of the precision assessment that is neglected in current recommendations. Sample sizes larger than 30 df are required if low levels of categorization error are to be achieved. [Copyright &y& Elsevier]

Abstract: The effect of precision study sample size is not considered in current recommendations for assessing bone mineral density (BMD) change. Intuitively, a larger sample size should provide greater confidence in the derived least significant change (LSC), which should translate into a more confident determination of change. We evaluated an empirical Monte Carlo simulation method for estimating the significance of an observed change in BMD that simultaneously considers the magnitude of the change, the LSC point estimate, and the precision study sample size. This method showed a progressive increase in the ability to identify BMD change using larger precision study sample sizes. Approaches that consider the error in the LSC estimate may provide more robust determinations of BMD change even when the precision study sample size is limited. [Copyright &y& Elsevier]

Objectives: The current World Health Organization (WHO) definition of osteoporosis, which is based on densitometry of lumbar and femoral regions, is extensively used for decision-making in clinical practice. Discordance in diagnosis of osteoporosis using this definition is a known phenomenon. The aim of this study was to evaluate the impact of such discordance and to assess the diagnostic value of using one skeletal site for screening purposes as opposed to the two sites required in the WHO criteria. Study design: Data was collected from 4188 individuals (3848 female); mean age = 53.4 years (standard deviation 11.8) referred to a community-based outpatient osteoporosis testing centre in Tehran, Iran. Methods: Dual-energy X-ray absorptiometry (DXA) was performed on L1-L4 lumbar spine and total hip for at[ cases. The DXA results were categorized according to WHO criteria. Sensitivity for each site was calculated as number of cases with T-score <-2.5 at that site divided by the total number of cases with T-score <-2.5 at any site. Results: Prevalence of osteoporosis diagnosis using lumbar DXA, femoral DXA, and WHO criteria (either of the sites) were 24.7%, 12.4%, and 27.8%, respectively. Sensitivity of lumbar DXA for diagnosis of osteoporosis (88.9%) was significantly higher than femoral DXA (44.6%, P<0.001); but this difference became non significant for men >-60 and women >-70 (P = 0.615 and P = 0.077, respectively). Agreement of the procedures in different sites (κ) was 0.40 (0.37 to 0.43). When proximal femur was considered as the reference, positive likelihood ratios of lumbar DXA to detect cases were 4.7 and 2.0 in younger and older groups, respectively. Conclusions: Concerning the high rate of discordance and low agreement between DXA results, the data obtained from each anatomical site cannot predict the condition of the other site. However, if use of a single assessment is intended for screening programs, public health authorities can develop... [ABSTRACT FROM AUTHOR]

Abstract: An estimated one in three adults aged 65 years or older falls each year, making falls a major health concern. Hip fractures are the most serious consequences of falls in elderly people. Identifying the characteristics of falls leading to hip fracture may provide information about high risk individuals, environment, and activities useful for the development of intervention strategies. Little is known, however, about the incidence and characteristics of falls leading to hip fracture in Middle Eastern countries. Therefore, the authors presented data from the Iranian Multicenter Study on Accidental Injuries, a prospective population-based study conducted in 9 provinces of Iran in 2003. All the hospitals serving about 9.5 million people in the study area were prospectively surveyed for any incident injury resulting from accidental events. A total of 2186 patients (1372 male, 814 female) were admitted due to any injurious fall events, where 572 (26.2%) of them suffered a hip fracture. Annual incidence rates of injurious fall events and related hip fractures were 116.3 and 30.4 per 100,000 person-years, respectively. These figures were 237.1 and 93.6 per 100,000 person-years for people over the age of 50 years, respectively. 71% of fall injuries and 76% of hip fractures occurred indoors. Among 450 patients with hip fractures ≥50 years of age, 61.8% arose from a fall from standing height or less. Only 1 in these 450 hip fractures occurred at the time of recreational activity. In multivariate logistic regression analysis, no factor was an independent predictor of hip fractures comparing to other fall-related injuries among younger participants (≥20 and <50 years). For older patients, falls from standing height or loss (odds ratio (OR) = 2.67), falls during walking (OR = 1.71), and falls on stairs (OR = 1.73) were detected as risk factors of hip fracture. Married persons and those falling from a ladder or other elevations were less likely to fracture their hip in this age group. Our data suggest that modification of the factors external to the homes is less likely to prevent more than a small proportion of fall-related hip fractures in Iran. Further studies on this topic have potential applications for developing preventive strategies. [Copyright &y& Elsevier]

Abstract: Osteoporosis is a major public health problem in the Western countries and is projected to have a similar impact in the Middle East. It has been suggested that peak bone mineral density (BMD), a major determinant of osteoporotic fractures later in life, may be lower in this part of the world compared with the Western world. The purpose of the Iranian Multicenter Osteoporosis Study was to determine peak bone mass in a randomly chosen sample of healthy Iranian subjects. A total of 5201 participants (2340 males, mean age 42.7±13.8) were recruited based on randomized clustered sampling from all regions of five major cities across the country. In women, peak lumbar BMD (1.182±0.127 g/cm2) occurred in the 29- to 33-yr age group, whereas peak total femur BMD (1.006±0.126 g/cm2) occurred in the 32- to 36-yr age group. In men, peak lumbar BMD (1.181±0.153 g/cm2) and femoral BMD (1.096±0.159 g/cm2) both occurred in the 20- to 24-yr age group. When standardized to mg/cm2 units using established formulas, Iranian peak bone mass values are comparable with that of Western countries and are generally higher than that of Eastern Asian and Middle Eastern countries. [Copyright &y& Elsevier]

• We aimed to determine the association between percentage body fat and incident fractures, separately for men and women. • We included 14,129 participants from the EPIC-Norfolk Prospective Population Cohort Study. • In women, a lower percentage body fat was associated with a higher risk of any fracture and specifically of hip fracture. • In men, the risk of any fracture did not change with percentage body fat, while the risk of hospitalisation for a hip fracture increased with percentage body fat. • These findings add to the important evidence base regarding the risk of a serious and prevalent adverse outcome. This cohort study aimed to determine the association between body fat percentage (BF%), incident fractures and calcaneal broadband ultrasound attenuation (BUA). Participants were drawn from the EPIC-Norfolk Prospective Population Cohort Study (median follow-up = 16.4 years). Cox models analysed the relationship between BF% and incident fractures (all and hip). Linear and restricted cubic spline (RCS) regressions modelled the relationship between BF% and BUA. 14,129 participants (56.2 % women) were included. There were 1283 and 537 incident all and hip fractures respectively. The participants had a mean (standard deviation) age of 61.5 (9.0) years for women and 62.9 (9.0) years for men. Amongst men, BF% was not associated with incident all fractures. While BF% < 23 % (median) was not associated with hip fractures, BF% > 23 % was associated with increased risk of hip fractures by up to 50 % (hazard ratio (95 % confidence interval) = 1.49 (1.06–2.12)). In women, BF% < 39 % (median) was associated with up to 32 % higher risk of all fractures (1.32 (1.13–1.44)), while BF% > 35 % was not associated with this outcome. Higher BF% was associated with lower risk of incident hip fractures in women. Higher BF% was associated with higher BUA amongst women. Higher BF% up to ~23 % was associated with higher BUA amongst men. Higher BF% is associated with lower risk of fractures in women. While there was no association between BF% and all fractures in men, increasing BF% >23 % was associated with higher risk of hip fractures in men. This appears to be independent of estimated bone mineral density. Fracture prevention efforts need to consider wider physical, clinical, and environmental factors. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Concerning prevalence of carpal tunnel syndrome (CTS) and the difficulties with electromyography (EMG) and nerve conduction studies (NCS), this study was designed to evaluate the power of somatosensory evoked potential (SSEP) in CTS diagnosis among Iranian patients. Patients and methods: SSEP was performed on 100 asymptomatic hands of 50 healthy participants (40 female, age range 38–59 years) and on 61 hands of 46 patients (39 female, age range 34–58 years). Mean difference between N20 latency of the middle finger and the wrist (median nerve innervation) as well as N20 latency of the third finger and the fifth finger (ulnar nerve innervation) were measured. Using receiver operating characteristic (ROC) curve analysis, the upper limits of these variables were defined as 6.0 and 1.5ms, respectively. Higher amounts in either of these variables were considered as positive SSEP for diagnosis of CTS. Measures of accuracy for SSEP were measured getting clinical diagnosis by two separate neurologists as the reference standard. In the patients’ group who underwent both techniques of SSEP and EMG–NCS, kappa statistic as the agreement coefficient between two procedures was calculated. Results: Sensitivity, specificity, and likelihood ratios for positive and negative results of SSEP in diagnosis of CTS were 70.4%, 91.0%, 7.83 and 0.32, respectively. Sensitivity of EMG–NCS in diagnosis of CTS was measured as 81.9%. Measure of agreement between two procedures (kappa) was calculated as 0.42. Conclusion: This study showed that positive results of SSEP might have a role in diagnosis of CTS. However, larger studies to demonstrate diagnostic power of SSEP in comparison with EMG–NCS seem necessary. [Copyright &y& Elsevier]