Alireza Moayyeri

The association between physical activity and osteoporotic fractures: a review of the evidence and implications for future research.

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.

Cohort Profile: TwinsUK and Healthy Ageing Twin Study

The UKs largest registry of adult twins, or TwinsUK Registry, started in 1992 and encompasses about 12000 volunteer twins from all over the United Kingdom. More than 70% of the registered twins have filled at least one detailed health questionnaire and about half of them undergone a baseline comprehensive assessment and two follow-up clinical evaluations. The most recent follow-up visit, known as Healthy Ageing Twin Study (HATS), involved 3125 female twins aged >40 years with at least one previous clinical assessment to enable inspection of longitudinal changes in ageing traits and their genetic and environmental components. The study benefits from several state-of-the-art OMICs studies including genome-wide association, next-generation genome and transcriptome sequencing, and epigenetic and metabolomic profiles. This makes our cohort as one of the most deeply phenotyped and genotyped in the world. Several collaborative projects in the field of epidemiology of complex disorders are ongoing in our cohort and interested researchers are encouraged to get in contact for future collaborations.

Lipidomics Profiling and Risk of Cardiovascular Disease in the Prospective Population-Based Bruneck Study

Background— The bulk of cardiovascular disease risk is not explained by traditional risk factors. Recent advances in mass spectrometry allow the identification and quantification of hundreds of lipid species. Molecular lipid profiling by mass spectrometry may improve cardiovascular risk prediction. Methods and Results— Lipids were extracted from 685 plasma samples of the prospective population-based Bruneck Study (baseline evaluation in 2000). One hundred thirty-five lipid species from 8 different lipid classes were profiled by shotgun lipidomics with the use of a triple-quadrupole mass spectrometer. Levels of individual species of cholesterol esters (CEs), lysophosphatidylcholines, phosphatidylcholines, phosphatidylethanolamines (PEs), sphingomyelins, and triacylglycerols (TAGs) were associated with cardiovascular disease over a 10-year observation period (2000–2010, 90 incident events). Among the lipid species with the strongest predictive value were TAGs and CEs with a low carbon number and double-bond content, including TAG(54:2) and CE(16:1), as well as PE(36:5) (P=5.1×10−7, 2.2×10−4, and 2.5×10−3, respectively). Consideration of these 3 lipid species on top of traditional risk factors resulted in improved risk discrimination and classification for cardiovascular disease (cross-validated &Dgr;C index, 0.0210 [95% confidence interval, 0.0010-0.0422]; integrated discrimination improvement, 0.0212 [95% confidence interval, 0.0031-0.0406]; and continuous net reclassification index, 0.398 [95% confidence interval, 0.175-0.619]). A similar shift in the plasma fatty acid composition was associated with cardiovascular disease in the UK Twin Registry (n=1453, 45 cases). Conclusions— This study applied mass spectrometry-based lipidomics profiling to population-based cohorts and identified molecular lipid signatures for cardiovascular disease. Molecular lipid species constitute promising new biomarkers that outperform the conventional biochemical measurements of lipid classes currently used in clinics.

Quantitative ultrasound of the heel and fracture risk assessment: an updated meta-analysis

SummaryMeta-analysis of prospective studies shows that quantitative ultrasound of the heel using validated devices predicts risk of different types of fracture with similar performance across different devices and in elderly men and women. These predictions are independent of the risk estimates from hip DXA measures.IntroductionClinical utilisation of heel quantitative ultrasound (QUS) depends on its power to predict clinical fractures. This is particularly important in settings that have no access to DXA-derived bone density measurements. We aimed to assess the predictive power of heel QUS for fractures using a meta-analysis approach.MethodsWe conducted an inverse variance random effects meta-analysis of prospective studies with heel QUS measures at baseline and fracture outcomes in their follow-up. Relative risks (RR) per standard deviation (SD) of different QUS parameters (broadband ultrasound attenuation [BUA], speed of sound [SOS], stiffness index [SI], and quantitative ultrasound index [QUI]) for various fracture outcomes (hip, vertebral, any clinical, any osteoporotic and major osteoporotic fractures) were reported based on study questions.ResultsTwenty-one studies including 55,164 women and 13,742 men were included in the meta-analysis with a total follow-up of 279,124 person-years. All four QUS parameters were associated with risk of different fracture. For instance, RR of hip fracture for 1 SD decrease of BUA was 1.69 (95% CI 1.43–2.00), SOS was 1.96 (95% CI 1.64–2.34), SI was 2.26 (95%CI 1.71–2.99) and QUI was 1.99 (95% CI 1.49–2.67). There was marked heterogeneity among studies on hip and any clinical fractures but no evidence of publication bias amongst them. Validated devices from different manufacturers predicted fracture risks with similar performance (meta-regression p values > 0.05 for difference of devices). QUS measures predicted fracture with a similar performance in men and women. Meta-analysis of studies with QUS measures adjusted for hip BMD showed a significant and independent association with fracture risk (RR/SD for BUA = 1.34 [95%CI 1.22–1.49]).ConclusionsThis study confirms that heel QUS, using validated devices, predicts risk of different fracture outcomes in elderly men and women. Further research is needed for more widespread utilisation of the heel QUS in clinical settings across the world.

Is QUS or DXA Better for Predicting the 10-Year Absolute Risk of Fracture?†‡

Although quantitative ultrasound (QUS) is known to be correlated with BMD and bone structure, its long‐term predictive power for fractures in comparison with DXA is unclear. 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. From 1455 participants (703 men) 65–76 yr of age at baseline, 79 developed a fracture over 10.3 ± 1.4 yr of follow‐up. In a sex‐stratified Cox proportional‐hazard model including age, height, body mass index, prior fracture, smoking, alcohol intake, and total hip BMD, a 1 SD decrease in BMD was associated with a hazard ratio (HR) for fracture of 2.26 (95% CI: 1.74–2.95). In the multivariable model with heel broadband ultrasound attenuation (BUA) in place of BMD, HR for a 1 SD decrease in BUA was 2.04 (95% CI: 1.55–2.69). Global measures of model fit showed relative superiority of the BMD model, whereas the area under the receiving operator characteristic (ROC) curve was slightly higher for the BUA model. Using both Cox models with BMD and BUA measures, we calculated exact 10‐yr absolute risk of fracture for all participants and categorized them in groups of <5%, 5% to <15%, and ≥15%. Comparison of groupings based on two models showed a total reclassification of 28.8% of participants, with the greatest reclassification (∼40%) among the intermediate‐ and high‐risk groups. This study shows that the power of QUS for prediction of fractures among the elderly is at least comparable to that of DXA. Given the feasibility and lower cost of ultrasound measurement in primary care, further studies to develop and validate models for prediction of 10‐yr risk of fracture using clinical risk factors and QUS are recommended.

Clinical course of ulcerative colitis in patients with and without primary sclerosing cholangitis

Background and Aim: We noticed in our practice that patients with ulcerative colitis (UC) who have developed primary sclerosing cholangitis (PSC) experience a milder course of colonic disease. Our objective in this study was to define whether or not there is any difference between UC activity and its course in patients with and without PSC.

Discordance in diagnosis of osteoporosis using spine and hip bone densitometry

BackgroundDiagnostic discordance for osteoporosis is the observation that the T-score of an individual patient varies from one key measurement site to another, falling into two different diagnostic categories identified by the World Health Organization (WHO) classification system. This study was conducted to evaluate the presence and risk factors for this phenomenon in a large sample of Iranian population.MethodsDemographic data, anthropometric measurements, and risk factors for osteoporosis were derived from a database on 4229 patients referred to a community-based outpatient osteoporosis testing center from 2000 to 2003. Dual-energy X-ray absorptiometry (DXA) was performed on L1–L4 lumbar spine and total hip for all cases. Minor discordance was defined as present when the difference between two sites was no more than one WHO diagnostic class. Major discordance was present when one site is osteoporotic and the other is normal. Subjects with incomplete data were excluded.ResultsIn 4188 participants (3848 female, mean age 53.4 ± 11.8 years), major discordance, minor discordance, and concordance of T-scores were seen in 2.7%, 38.9% and 58.3%, respectively. In multivariate logistic regression analysis, older age, menopause, obesity, and belated menopause were recognized as risk factors and hormone replacement therapy as a protective factor against T-score discordance.ConclusionThe high prevalence of T-score discordance may lead to problems in interpretation of the densitometry results for some patients. This phenomenon should be regarded as a real and prevalent finding and physicians should develop a particular strategy approaching to these patients.

Official Positions for FRAX Bone Mineral Density and FRAX Simplification From Joint Official Positions Development Conference of the International Society for Clinical Densitometry and International Osteoporosis Foundation on FRAX

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.

Measured Height Loss Predicts Fractures in Middle-Aged and Older Men and Women: The EPIC-Norfolk Prospective Population Study†

In this large population‐based prospective study among middle‐aged and older men and women, we found that height loss of >2 cm over a period of 4 yr is a significant predictor of future fractures. Serial measurement of height is, therefore, recommended among the elderly people.

Obesity and associated cardiovascular risk factors in Iranian children: a cross-sectional study.

Background: Obesity is a growing public health problem in developing countries considering its association with cardiovascular risk factors. Relationship between childhood obesity and these risk factors has not been attested in the Iranian population before. The aim of the present study was to investigate frequency of cardiovascular risk factors and their association with severity of obesity in a sample of Iranian obese children.