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We studied the characteristics of patients prescribed osteoporosis medication and patterns of use in European databases. Patients were mostly female, older, had hypertension. There was suboptimal persistence particularly for oral medications. Our findings would be useful to healthcare providers to focus their resources on improving persistence to specific osteoporosis treatments., Purpose: To characterise the patients prescribed osteoporosis therapy and describe the drug utilization patterns., Methods: We investigated the treatment patterns of bisphosphonates, denosumab, teriparatide, and selective estrogen receptor modulators (SERMs) in seven European databases in the United Kingdom, Italy, the Netherlands, Denmark, Spain, and Germany. In this cohort study, we included adults aged ≥ 18 years, with ≥ 1 year of registration in the respective databases, who were new users of the osteoporosis medications. The study period was between 01 January 2018 to 31 January 2022., Results: Overall, patients were most commonly initiated on alendronate. Persistence decreased over time across all medications and databases, ranging from 52-73% at 6 months to 29-53% at 12 months for alendronate. For other oral bisphosphonates, the proportion of persistent users was 50-66% at 6 months and decreased to 30-44% at 12 months. For SERMs, the proportion of persistent users at 6 months was 40-73% and decreased to 25-59% at 12 months. For parenteral treatment groups, the proportions of persistence with denosumab were 50-85% (6 month), 30-63% (12 month) and with teriparatide 40-75% (6 month) decreasing to 21-54% (12 month). Switching occurred most frequently in the alendronate group (2.8-5.8%) and in the teriparatide group (7.1-14%). Switching typically occurred in the first 6 months and decreased over time. Patients in the alendronate group most often switched to other oral or intravenous bisphosphonates and denosumab., Conclusion: Our results show suboptimal persistence to medications that varied across different databases and treatment switching was relatively rare., (© 2023. The Author(s).)

Mortality risk declined over time. Patients with fragility hip fracture experienced an approximate ninefold excess mortality, peaking shortly after fracture, in comparison with that of the general population. Continuous efforts in lowering the occurrence of hip fracture have the potential to improve the survival of the elderly population in China., Purpose: Hip fractures in older adults often lead to an elevated risk of death. However, few studies investigated mortality risk following hip fracture in mainland China. This retrospective cohort study aimed to evaluate the crude mortality and excess mortality after fragility hip fractures in Lishui residents aged 50 years and older., Methods: Patients having a fragility hip fracture between October 2013 and August 2019 were identified from the Lishui District Inpatient Data Collection and followed up until August 2020. Death information was ascertained from the linked death registry records. We calculated the follow-up mortality rate and corresponding 95% confidence intervals (CIs) as well as the standard mortality ratios (SMRs) in comparison with the mortality rates of Lishui residents., Results: During the study period, a total of 808 patients (63.4% females) with an average age of 75 years were admitted for fragility hip fractures. The 1st, 2nd, and 3rd year follow-up mortality rates were 16.51, 6.06, and 5.03 per 100 person-year, respectively. The SMRs were 8.46 (6.94, 9.97), 5.74 (4.86, 6.63), and 4.63 (3.98, 5.27) for the 1st, 2nd, and 3rd year following fragility hip fracture., Conclusion: Although mortality risk declined over time, patients with fragility hip fracture experienced an approximate ninefold excess mortality, peaking shortly after fracture, in comparison with that of the general population. Continuous efforts in lowering the occurrence of hip fracture have the potential to improve the survival of the elderly population in China., (© 2023. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

Background: This cohort study aimed to determine the association between body fat percentage (BF%), incident fractures and calcaneal broadband ultrasound attenuation (BUA)., Methods: 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., Results: 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., Conclusions: 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., Competing Interests: Declaration of competing interest The authors declare that they have no competing interest., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Bone mineral density (BMD) is an established measure used to diagnose patients with osteoporosis. In clinical trials, change in BMD has been shown to provide a reliable estimate of fracture risk reduction, and achieved BMD T-score has been shown to reflect the near-term risk of fracture. We aimed to test the association between BMD T-score and fracture risk in patients treated for osteoporosis in a real-world setting. This retrospective, observational cohort study included Swedish females aged ≥55 years who had a total hip BMD measurement at one of three participating clinics. Patients were separated into two cohorts: bisphosphonate-treated and bisphosphonate-naïve prior to BMD measurement, stratified by age and prior nonvertebral fracture status. The primary outcome was cumulative incidence of clinical fractures within 24 months of BMD measurement, with other fracture types included as secondary outcomes. Associations between T-score and fracture risk were estimated using proportional hazards regression and restricted cubic splines. A total of 15,395 patients were analyzed: 11,973 bisphosphonate-naïve and 3422 bisphosphonate-treated. In the 24 months following BMD measurement, 6.3% (95% confidence interval [CI], 5.9-6.7) of bisphosphonate-naïve and 8.4% (95% CI, 7.5-9.4) of bisphosphonate-treated patients experienced a clinical fracture. Strong inverse relationships between BMD T-score and fracture incidence were observed in both cohorts. Among bisphosphonate-naïve patients, this relationship appeared to plateau around T-score -1.5, indicating smaller marginal reductions in fracture risk above this value; bisphosphonate-treated patients showed a more consistent marginal change in fracture risk across the evaluated T-scores (-3.0 to -0.5). Trends remained robust regardless of age and prior fracture status. This real-world demonstration of a BMD-fracture risk association in both bisphosphonate-naïve and bisphosphonate-treated patients extends evidence from clinical trials and recent meta-regressions supporting the suitability of total hip BMD as a meaningful outcome for the clinical management of patients with osteoporosis. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)., (© 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).)

The metabolic state of the body can be a major determinant of bone health. We used a Mendelian randomization approach to identify metabolites causally associated with bone mass to better understand the biological mechanisms of osteoporosis. We tested bone phenotypes (femoral neck, total hip, and lumbar spine bone mineral density [BMD]) for association with 280 fasting blood metabolites in 6055 women from TwinsUK cohort with genomewide genotyping scans. Causal associations between metabolites and bone phenotypes were further assessed in a bidirectional Mendelian randomization study using genetic markers/scores as instrumental variables. Significant associations were replicated in 624 participants from the Hong Kong Osteoporosis Study (HKOS). Fifteen metabolites showed direct associations with bone phenotypes after adjusting for covariates and multiple testing. Using genetic instruments, four of these metabolites were found to be causally associated with hip or spine BMD. These included androsterone sulfate, epiandrosterone sulfate, 5alpha-androstan-3beta17beta-diol disulfate (encoded by CYP3A5), and 4-androsten-3beta17beta-diol disulfate (encoded by SULT2A1). In the HKOS population, all four metabolites showed significant associations with hip and spine BMD in the expected directions. No causal reverse association between BMD and any of the metabolites were found. In the first metabolome-genomewide Mendelian randomization study of human bone mineral density, we identified four novel biomarkers causally associated with BMD. Our findings reveal novel biological pathways involved in the pathogenesis of osteoporosis. © 2017 American Society for Bone and Mineral Research., (© 2017 American Society for Bone and Mineral Research.)

Quantitative ultrasound of the heel captures heel bone properties that independently predict fracture risk and, with bone mineral density (BMD) assessed by X-ray (DXA), may be convenient alternatives for evaluating osteoporosis and fracture risk. We performed a meta-analysis of genome-wide association (GWA) studies to assess the genetic determinants of heel broadband ultrasound attenuation (BUA; n = 14 260), velocity of sound (VOS; n = 15 514) and BMD (n = 4566) in 13 discovery cohorts. Independent replication involved seven cohorts with GWA data (in silico n = 11 452) and new genotyping in 15 cohorts (de novo n = 24 902). In combined random effects, meta-analysis of the discovery and replication cohorts, nine single nucleotide polymorphisms (SNPs) had genome-wide significant (P < 5 × 10(-8)) associations with heel bone properties. Alongside SNPs within or near previously identified osteoporosis susceptibility genes including ESR1 (6q25.1: rs4869739, rs3020331, rs2982552), SPTBN1 (2p16.2: rs11898505), RSPO3 (6q22.33: rs7741021), WNT16 (7q31.31: rs2908007), DKK1 (10q21.1: rs7902708) and GPATCH1 (19q13.11: rs10416265), we identified a new locus on chromosome 11q14.2 (rs597319 close to TMEM135, a gene recently linked to osteoblastogenesis and longevity) significantly associated with both BUA and VOS (P < 8.23 × 10(-14)). In meta-analyses involving 25 cohorts with up to 14 985 fracture cases, six of 10 SNPs associated with heel bone properties at P < 5 × 10(-6) also had the expected direction of association with any fracture (P < 0.05), including three SNPs with P < 0.005: 6q22.33 (rs7741021), 7q31.31 (rs2908007) and 10q21.1 (rs7902708). In conclusion, this GWA study reveals the effect of several genes common to central DXA-derived BMD and heel ultrasound/DXA measures and points to a new genetic locus with potential implications for better understanding of osteoporosis pathophysiology.

The rate of bone loss varies across the aging period via multiple complex mechanisms. Therefore, the role of genetic factors on bone loss may also change similarly. In this study, we investigated the effect of age on the genetic component of bone loss in a large twin-based longitudinal study. During 17 years of follow-up in TwinsUK and Healthy Ageing Twin Study (HATS), 15,491 hip and lumbar spine dual-energy X-ray absorptiometry (DXA) scans were performed in 7056 twins. Out of these subjects, 2716 female twins aged >35 years with at least two scans separated for >4 years (mean follow-up 9.7 years) were included in this analysis. We used a mixed-effects random-coefficients regression model to predict hip and spine bone mineral density (BMD) values for exact ages of 40, 45, 50, 55, 60, 65, 70, 75, and 80 years, with adjustment for baseline age, weight, height, and duration of hormone replacement therapy. We then estimated heritability of the changes in BMD measures between these age ranges. Heritability estimates for cross-sectional hip and spine BMD were high (ranging between 69% and 88%) at different ages. Heritability of change of BMD was lower and more variable, generally ranging from 0% to 40% for hip and 0% to 70% for spine; between age 40 and 45 years genetic factors explained 39.9% (95% confidence interval [CI], 25%-53%) of variance of BMD loss for total hip, 46.4% (95% CI, 32%-58%) for femoral neck, and 69.5% (95% CI, 59%-77%) for lumbar spine. These estimates decreased with increasing age, and there appeared to be no heritability of BMD changes after the age of 65 years. There was some evidence at the spine for shared genetic effects between cross-sectional and longitudinal BMD. Whereas genetic factors appear to have an important role in bone loss in early postmenopausal women, nongenetic mechanisms become more important determinants of bone loss with advanced age., (Copyright © 2012 American Society for Bone and Mineral Research.)

Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 × 10(-8)). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P < 5 × 10(-4), Bonferroni corrected), of which six reached P < 5 × 10(-8), including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility.

While estimates of relative risks associated with risk factors such as age and bone mineral density (BMD) may be of interest for etiologic and comparative purposes, clinical questions such as who might benefit most from preventive interventions or BMD monitoring depend on estimates of absolute fracture risk. The European prospective investigation into cancer (EPIC)-Norfolk study included 25,311 participants (11,476 men) aged 4,079 years in 1993-1997. All participants were followed for osteoporotic fractures to March 2007. Ten-year absolute risk of fracture in men and women were calculated using the baseline survivor function in multivariable Cox proportional-hazards models adjusting for age, sex, history of fractures, body mass index, smoking, and alcohol intake. In comparison of those without history of fracture versus those with history of fracture, the 10-year absolute risk of any fracture in men ranged from 1.0 vs. 1.2% at age 40 years to 3.0 vs. 4.4% at age 75 years. The respective estimates in women ranged from 0.7 vs. 1.0% at age 40 years to 9.3 vs. 17.2% at age 75 years. Statistically significant interaction between age and sex was found (P < 0.001), which contributed to the differences in predicted absolute fracture risks for men and women at different ages. Our study shows the need for population-specific data to develop efficient well calibrated algorithms for assessment of fracture risk. The interaction observed between sex and age points to the need for further prospective studies among men.

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.

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 all 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 > or = 60 and women > or = 70 (P=0.615 and P=0.077, respectively). Agreement of the procedures in different sites (kappa) 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 different strategies for different age groups of their population. We propose lumbar DXA for the younger group (men < 60 and women < 70) and femoral densitometry for the older.

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.

The extent to which low-frequency (minor allele frequency (MAF) between 1-5%) and rare (MAF ≤ 1%) variants contribute to complex traits and disease in the general population is mainly unknown. Bone mineral density (BMD) is highly heritable, a major predictor of osteoporotic fractures, and has been previously associated with common genetic variants, as well as rare, population-specific, coding variants. Here we identify novel non-coding genetic variants with large effects on BMD (ntotal = 53,236) and fracture (ntotal = 508,253) in individuals of European ancestry from the general population. Associations for BMD were derived from whole-genome sequencing (n = 2,882 from UK10K (ref. 10); a population-based genome sequencing consortium), whole-exome sequencing (n = 3,549), deep imputation of genotyped samples using a combined UK10K/1000 Genomes reference panel (n = 26,534), and de novo replication genotyping (n = 20,271). We identified a low-frequency non-coding variant near a novel locus, EN1, with an effect size fourfold larger than the mean of previously reported common variants for lumbar spine BMD (rs11692564(T), MAF = 1.6%, replication effect size = +0.20 s.d., Pmeta = 2 × 10(-14)), which was also associated with a decreased risk of fracture (odds ratio = 0.85; P = 2 × 10(-11); ncases = 98,742 and ncontrols = 409,511). Using an En1(cre/flox) mouse model, we observed that conditional loss of En1 results in low bone mass, probably as a consequence of high bone turnover. We also identified a novel low-frequency non-coding variant with large effects on BMD near WNT16 (rs148771817(T), MAF = 1.2%, replication effect size = +0.41 s.d., Pmeta = 1 × 10(-11)). In general, there was an excess of association signals arising from deleterious coding and conserved non-coding variants. These findings provide evidence that low-frequency non-coding variants have large effects on BMD and fracture, thereby providing rationale for whole-genome sequencing and improved imputation reference panels to study the genetic architecture of complex traits and disease in the general population.

Summary: We estimated the short-term impact of fragility fractures on community-dwelling women in five countries. Women with fragility fractures reported significantly more difficulties performing activities of daily living and significantly higher levels of lost productivity and caregiver support than those without fractures; results highlight the multi-country indirect burden of fragility fractures. Introduction: To estimate the impact of fragility fractures on activities of daily living (ADL), productivity loss and caregiver support in women with a recent fragility fracture. Methods: This multi-centre cross-sectional study enrolled community-dwelling women aged ≥ 50 years in South Korea, Spain, Germany, Australia and the United States. The fragility fracture cohort consisted of women with an index fragility fracture in the past 12 months; the fracture free cohort consisted of women with no fracture in the 18 months prior to study enrolment. Study participants completed three validated questionnaires: Lawton Instrumental ADL (IADL), Physical Self-Maintenance Scale (PSMS) and iMTA Productivity Cost Questionnaire (iPCQ). Results: In total, 1,253 participants from 41 sites across the five countries were included. Compared with the fracture free cohorts, fragility fracture cohorts had significantly lower function and were more dependent on support (p < 0.05 in all countries for Lawton IADL, and in South Korea, Spain, Australia and the United States for PSMS), significantly higher hours of paid absenteeism (p < 0.05, Spain, Germany, Australia), significantly higher unpaid lost productivity (p < 0.05, South Korea, Spain, Germany), significantly more days of paid help received in the home (p < 0.05 South Korea, Spain and the United States), and significantly more days of unpaid help from family members or friends (p < 0.05, all countries). Conclusion: In this multi-national study, fragility fractures in community-dwelling ≥ 50 years women were associated with several outcomes indicating higher indirect burden and lower quality of life, including more difficulties performing ADL and higher levels of lost productivity and caregiver support. [ABSTRACT FROM AUTHOR]

The objective of this work was to estimate the incidence rate of cardiovascular disease (CVD) events (myocardial infarction, stroke, or CVD death) at 1 year among three cohorts of patients at high risk of fracture (osteoporosis, previous fracture, and anti‐osteoporosis medication) and to identify the key risk factors of CVD events in these three cohorts. To do so, this prospective cohort study used data from the Clinical Practice Research Datalink, a primary care database from United Kingdom. Major adverse cardiovascular events (MACE, a composite outcome for the occurrence of either myocardial infarction [MI], stroke, or CVD death) were identified in patients aged 50 years or older at high or imminent fracture risk identified in three different cohorts (not mutually exclusive): recently diagnosed with osteoporosis (OST, n = 65,295), incident fragility fracture (IFX, n = 67,065), and starting oral bisphosphonates (OBP, n = 145,959). About 1.90%, 4.39%, and 2.38% of the participants in OST, IFX, and OBP cohorts, respectively, experienced MACE events. IFX was the cohort with the higher risk: MACE incidence rates (cases/1000 person‐years) were 19.63 (18.54–20.73) in OST, 52.64 (50.7–54.5) in IFX, and 26.26 (25.41–27.12) in OBP cohorts. Risk of MACE events at 1 year was predicted in the three cohorts. Models using a set of general, CVD, and fracture candidates selected by lasso regression had a good discrimination (≥70%) and internal validity and generally outperformed the models using only the CVD risk factors of general population listed in QRISK tool. Main risk factors common in all MACE models were sex, age, smoking, alcohol, atrial fibrillation, antihypertensive medication, prior MI/stroke, established CVD, glomerular filtration rate, systolic blood pressure, cholesterol levels, and number of concomitant medicines. Identified key risk factors highlight the differences of patients at high risk of fracture versus general population. Proposed models could improve prediction of CVD events in patients with osteoporosis in primary care settings. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR). [ABSTRACT FROM AUTHOR]

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: Both stroke and osteoporosis are prevalent conditions among the elderly. With increasing life expectancy across the world, despite better preventative measures, the incidence of both conditions is set to rise in the ageing populations. Alongside with sharing several common risk factors, the current evidence suggests that these conditions are risk factors for each other albeit more clear support for the effects of stroke on bone health. In this article, we present aetiopathophysiology of these two conditions and the current evidence of impact on each other particularly the impact of stroke on bone health. We also provide suggestions for improving bone health in people living with stroke based on the currently available evidence. [ABSTRACT FROM AUTHOR]

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]

The article discusses a study on the predictive capability of quantitative ultrasound (QUS) and dual x-ray absorptiometry (DXA) in terms of the 10-year absolute risk of fracture. It notes that DXA stands as the accepted reference method in bone mass density (BMD) measurement while a decline in BMD is linked to an increased risk of fracture. Under the study, the participants were subjected to either hip BMD measurement and QUS assessment. Results show that QUS assessment exhibited performance that is similar to that of DXA in predicting fracture risks.

This article discusses the results of a research study conducted to measure forced expiratory volume (FEV) as a means of predicting the risks of osteoporosis and hip fracture in a population between 42 and 81 years of age. The study finds that low respiratory function increases the risks of osteoporosis and hip fracture and suggests FEV as an effective method of identifying risk.

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.

This article focuses on a prospective population study on the relationship between height loss and fractures. The article contains an introduction, materials and methods, results, conclusions, as well as charts and graphs. The study found that in middle-aged and older men and women, a height loss of greater than 0.5 centimeters increased risk of hip and other fractures.

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: 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]

Background: Diagnostic 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. Methods: Demographic 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. Results: In 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 Tscore discordance. Conclusion: The 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. [ABSTRACT FROM AUTHOR]