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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: 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]

The article reports on the results of research which was conducted in an effort to perform a heteroscedastic regression analysis of the factors affecting bone mineral density monitoring in patients with osteoporosis. Researchers found that with samples of men and women, heteroscedastic regression outperformed models that assumed homogeneous variance and that it is a powerful tool in analyzing longitudinal bone mineral data that can be used to generate individualized predictions of bone mineral density change.

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]

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]