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Context Fragility fracture is a significant public health problem because it is associated with increased mortality. We want to find out whether the risk of fracture can be predicted from the time of birth. Objective To examine the association between a polygenic risk score (PRS) and lifetime fracture risk. Methods This population-based prospective study involved 3515 community-dwelling individuals aged 60+ years who have been followed for up to 20 years. Femoral neck bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry. A PRS was created by summing the weighted number of risk alleles for each single nucleotide polymorphism using BMD-associated coefficients. Fragility fractures were radiologically ascertained, whereas mortality was ascertained through a state registry. Residual lifetime risk of fracture (RLRF) was estimated by survival analysis. Results The mortality-adjusted RLRF for women and men was 36% (95% CI, 34%-39%) and 21% (18%-24%), respectively. Individuals with PRS > 4.24 (median) had a greater risk (1.2-fold in women and 1.1-fold in men) than the population average risk. For hip fracture, the average RLRF was 10% (95% CI, 8%-12%) for women and ∼5% (3%-7%) for men; however, the risk was significantly increased by 1.5-fold and 1.3-fold for women and men with high PRS, respectively. Conclusion A genetic profiling of BMD-associated genetic variants is associated with the residual lifetime risk of fracture, suggesting the potential for incorporating the polygenic risk score in personalized fracture risk assessment.

Muscle strength and physical performance are associated with incident fractures and mortality. However, their role in the risk of subsequent fracture and postfracture mortality is not clear. We assessed the association between muscle strength (grip strength) and performance (gait speed and chair stands time) and the risk of subsequent fracture and mortality in 830 men with low-trauma index fracture, who participated in the Osteoporotic Fractures in Men (MrOS) USA Study and had their index measurements assessed within 5 years prior to the index fracture. The annual decline in muscle strength and performance following index fracture, estimated using linear mixed-effects regression, was also examined in relation to mortality. The associations were assessed using Cox proportional hazards models adjusted for age, femoral neck bone mineral density (FN BMD), prior fractures, falls, body mass index (BMI), index fracture site, lifestyle factors, and comorbidities. Over a median follow-up of 3.7 (interquartile range [IQR], 1.3-8.1) years from index fracture to subsequent fracture, 201 (24%) men had a subsequent fracture and over 5.1 (IQR, 1.8-9.6) years to death, and 536 (65%) men died. Index measurements were not associated with subsequent fracture (hazard ratios [HRs] ranging from 0.97 to 1.07). However, they were associated with postfracture mortality. HR (95% confidence interval [CI]) per 1 standard deviation (1-SD) decrement in grip strength: HR 1.12 (95% CI, 1.01-1.25) and gait speed: HR 1.14 (95% CI, 1.02-1.27), and 1-SD increment in chair stands time: HR 1.08 (95% CI, 0.97-1.21). Greater annual declines in these measurements were associated with higher mortality risk, independent of the index values and other covariates. HR (95% CI) per 1-SD annual decrement in change in grip strength: HR 1.15 (95% CI, 1.01-1.33) and in gait speed: HR 1.38 (95% CI, 1.13-1.68), and 1-SD annual increment in chair stands time: HR 1.28 (95% CI, 1.07-1.54). Men who were unable to complete one or multiple tests had greater risk of postfracture mortality (24%-109%) compared to those performed all tests. It remains to be seen whether improvement in these modifiable factors can reduce postfracture mortality. © 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).

The analysis of cell-free DNA (cfDNA) from plasma offers great promise for the earlier detection of cancer. At present, changes in DNA sequence, methylation, or copy number are the most sensitive ways to detect the presence of cancer. To further increase the sensitivity of such assays with limited amounts of sample, it would be useful to be able to evaluate the same template molecules for all these changes. Here, we report an approach, called MethylSaferSeqS, that achieves this goal, and can be applied to any standard library preparation method suitable for massively parallel sequencing. The innovative step was to copy both strands of each DNA-barcoded molecule with a primer that allows the subsequent separation of the original strands (retaining their 5-methylcytosine residues) from the copied strands (in which the 5-methylcytosine residues are replaced with unmodified cytosine residues). The epigenetic and genetic alterations present in the DNA molecules can then be obtained from the original and copied strands, respectively. We applied this approach to plasma from 265 individuals, including 198 with cancers of the pancreas, ovary, lung, and colon, and found the expected patterns of mutations, copy number alterations, and methylation. Furthermore, we could determine which original template DNA molecules were methylated and/or mutated. MethylSaferSeqS should be useful for addressing a variety of questions relating genetics and epigenetics.

Background: Vertebral fracture is both common and serious among adults, yet it often goes undiagnosed. The aims of this study were to develop a shape-based algorithm (SBA) for the automatic identification of vertebral fractures. Results: At the person level, the SBA achieved a sensitivity of 100% and specificity of 61% (95% CI, 51-72%). At the vertebral level, the SBA achieved a sensitivity of 84% (95% CI, 72% to 93%), a specificity of 88% (95% CI, 85% to 90%). On average, the SBA took 0.3 seconds to assess one X-ray. Conclusions: The SBA developed here is a fast and efficient tool that can be used to systematically screen for asymptomatic vertebral fractures and reduce the workload of healthcare professionals. Methods: The study included 50participants whose plain thoracolumbar spine X-rays (n = 144) were taken. Clinical diagnosis of vertebral fracture (grade 0 to 3) was made by rheumatologists using Genant's semiquantitative method. The SBA algorithm was developed to determinethe ratio of vertebral body height loss. Based on the ratio, SBA classifies a vertebra into 4 classes: 0=normal, 1=mild fracture, 2=moderate fracture, 3=severe fracture). The concordance between clinical diagnosis and SBA-based classification was assessed at both personal and vertebral levels.

Little is known about the trends in colorectal cancer (CRC) in Vietnam. We aimed to investigate the trends in epidemiology and anatomical subsites of CRC in Ho Chi Minh City, Vietnam.Based on the Ho Chi Minh City Cancer Registry data during 1996-2015, we calculated the average annual percent changes (AAPCs) of the age-standardized incidence rates (ASRs) by sex, age groups, and anatomical subsites, using joinpoint regressions analysis. We further performed age-period-cohort (APC) analysis using the United States National Cancer Institute's web-based statistical tool to explore the underlying reason for the incidence trend.Over 20 years the overall ASR of CRC increased from 10.5 to 17.9 per 100,000, a 1.7-fold increase. CRC incidence elevated more rapidly in men (AAPC 4.7, 95%CI 2.2-7.3) than in women (AAPC 2.6, 95%CI 0.6-4.8). The highest and lowest increasing rates of ASRs were observed in the 50-64-year-old age group (AAPC 5.3, 95%CI 2.8-7.9) and 50-year-old age group (AAPC 1.1, 95%CI -0.7 to 2.9), respectively. Regarding subsites, rectal cancer had the highest rate of increase (AAPC 3.3, 95%CI 1.0-5.7). Furthermore, the APC analysis indicated significant increases in CRC incidence in birth cohorts after 1975 in both genders.The CRC incidence in Ho Chi Minh City increased, with the more prominent rates being among men and older populations, in rectal subsites, and in people born after 1975. The upward trend of CRC incidence in Ho Chi Minh City may be due to the adoption of a westernized lifestyle.

© 2018 Elsevier Inc. Purpose: Low trauma rib fracture (hereinafter, rib fracture) is common in the elderly, but its risk factors and mortality consequence are rarely studied. We sought to define the epidemiology of rib fracture and the association between rib fracture and postfracture mortality. Methods: The study was part of the Dubbo Osteoporosis Epidemiology Study, which was designed as a population-based prospective study, and consisted of 2041 women and men (aged ≥ 60). The incidence of rib fracture was ascertained from X-ray reports. Bone mineral density (BMD) was measured by DXA (GE-Lunar). The time-dependent Cox model was used to access the relationship between rib fracture and mortality. Results: During the median follow-up of 13 years, 59 men and 78 women had sustained a rib fracture, making the annual incidence of 4.8/1000 person-years. Each SD (0.15 g/cm 2 ) lower in femoral neck BMD was associated with ~2-fold increase in the hazard of fracture (hazard ratio [HR] 1.9; 95% CI, 1.4 to 2.6 in men; and HR 2.1; 95% CI, 1.6 to 2.8 in women). Among those with a rib fracture, the incidence of subsequent fractures was 10.2/100 person-years. Compared with those without a fracture, the risk of mortality among those with a fracture was increased by ~7.8-fold (95% CI, 2.7 to 22.5) in men and 4.9-fold (95% CI 2.0 to 11.8) in women within the first year postfracture. Conclusions: A rib fracture signifies an increased risk of subsequent fractures and mortality. The increased risk of mortality during the first 2.5 years postfracture suggests a window of opportunity for treatment.

We aimed to compare the discriminative power of prognostic models for early prediction of women at risk for the development of gestational diabetes mellitus (GDM) using four currently recommended diagnostic criteria based on the 75-g oral glucose tolerance test (OGTT). We also described the potential effect of application of the models into clinical practice.A prospective cross-sectional study of 2,772 pregnant women was conducted at a referral maternity center in Vietnam. GDM was determined by the American Diabetes Association (ADA), International Association of the Diabetes and Pregnancy Study Groups (IADPSG), Australasian Diabetes in Pregnancy Society (ADIPS), and World Health Organization (WHO) criteria. Prognostic models were developed using the Bayesian model averaging approach, and discriminative power was assessed by area under the curve. Different thresholds of predicted risk of developing GDM were applied to describe the clinical impact of the diagnostic criteria.The magnitude of GDM varied substantially by the diagnostic criteria: 5.9% (ADA), 20.4% (IADPSG), 20.8% (ADIPS), and 24.3% (WHO). The ADA prognostic model, consisting of age and BMI at booking, had the best discriminative power (area under the curve of 0.71) and the most favorable cost-effective ratio if implemented in clinical practice. Selective screening of women for GDM using the ADA model with a risk threshold of 3% gave 93% sensitivity for identification of women with GDM with a 27% reduction in the number of OGTTs required.A simple prognostic model using age and BMI at booking could be used for selective screening of GDM in Vietnam and in other low- and middle-income settings.