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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.

Background Jumping mechanography is a technology for quantitatively assessing muscular function and balance in older adults. This study sought to define the association between jumping mechanography parameters and fall risk in Vietnamese individuals. Methods The study involved 375 women and 244 men aged 50 years and older, who were recruited from the general population in Ho Chi Minh City (Vietnam). The individuals had been followed for 2 years. At baseline, Esslinger Fitness index (EFI), jumping power, force, velocity of lower limbs, and the ability to maintain balance were measured by a Leonardo Mechanograph Ground Reaction Force system (Novotec Medical, Pforxheim, Germany). The incidence of falls during the follow‐up period was ascertained from self‐report. Logistic regression analysis was used to analyse the association between jumping mechanography parameters and fall risk. Results The average age of participants at baseline was 56.7 years (SD 5.85). During the 2 year follow‐up, 92 falls were reported, making the incidence of fall at ~15% [95% confidence interval (CI), 12.1 to 18.2]. The incidence of fall increased with advancing age, and women had a higher incidence than men (17.6% vs. 10.7%; P = 0.024). In univariate analysis, maximal velocity [odds ratio (OR) 0.65; 95% CI, 0.52 to 0.82], maximal force (OR 0.83; 95% CI, 0.65 to 1.04), and maximal power (OR 0.68; 95% CI, 0.52 to 0.88) were each significantly associated with fall risk. EFI was not significantly associated with fall risk (OR 1.09; 95% CI, 0.86 to 1.39). However, in a multiple logistic regression model, greater maximum velocity was associated with lower odds of fall (OR 0.38; 95% CI, 0.16 to 0.92). Conclusions These data suggest that jumping mechanography is a useful tool for assessing fall risk in older adults of Vietnamese background.

One of the most intriguing characteristics of cell-free DNA (cfDNA) from plasma is the sequence at the ends of the fragments. Previous studies have shown that these end-sequences are somewhat different in cancer patients than in healthy individuals. While investigating this characteristic, we noticed that the bases at the 5’-ends of a double-stranded fragment were highly correlated with the GC content of that particular fragment. This led us to develop a method, called MendSeqS (Modified End-based sequencing System), that incorporates the correlation between end-motifs and GC content into the analysis of shallow (0.5x) whole genome sequencing (WGS). When applied to plasma samples, MendSeqS was able to classify patients with a sensitivity of 96% at 98% specificity in a cohort comprised of 107 individuals evaluated in our laboratory (43 with cancer and 64 without). In cohorts evaluated in three other laboratories, comprising a total of 401 individuals (193 with cancer and 208 without), MendSeqS achieved a sensitivity of 87% at 98% specificity. MendSeqS could in principle be combined with other methods of cfDNA analysis to enhance cancer detection.

Background The burden and trend of thyroid cancer in Vietnam have not been well documented. This study aimed to investigate the trends in incidence and histological pattern of thyroid cancer in Ho Chi Minh City from 1996 to 2015. Methods A population-based study retrieved data from the Ho Chi Minh City Cancer Registry during 1996–2015. Trends in the incidence of thyroid cancer were investigated based on age, gender, and histology for each 5-year period. Annual percentage change (APC) in incidence rates was estimated using Joinpoint regression analysis. Results In the study period, there were 5953 thyroid cancer cases (men-to-women ratio 1:4.5) newly diagnosed in Ho Chi Minh City with the mean age of 42.9 years (±14.9 years). The age-standardized incidence rate of thyroid cancer increased from 2.4 per 100,000 during 1996–2000 (95% confidence interval [95% CI]: 2.2–2.6) to 7.5 per 100,000 during 2011–2015 (95% CI: 7.3–7.9), corresponded to an overall APC of 8.7 (95% CI 7.6–9.9). The APC in men and women was 6.2 (95% CI: 4.2–8.2) and 9.2 (95% CI: 8.0–10.4), respectively. The incidence rate in the Conclusions There were appreciable increases in the age-standardized incidence rate of thyroid cancer in both genders, mainly contributed by the papillary subtype. The age of patients at diagnosis decreased gradually. The widespread utilization of advanced diagnostic techniques and healthcare accessibility improvement might play a potential role in these trends. Further investigations are needed to comprehend the risk factors and trends fully.

ObjectivesCalcaneal quantitative ultrasound measurement (QUS) has been considered an alternative to dual-energy X-ray absorptiometry (DXA) based bone mineral density (BMD) for assessing bone health. This study sought to examine the utility of QUS as an osteoporosis screening tool by evaluating the correlation between QUS and DXA.MethodsThe study was a part of the Vietnam Osteoporosis Study that involved 1270 women and 773 men aged 18 years and older. BMD at the femoral neck, total hip and lumbar spine was measured using DXA. Osteoporosis was diagnosed based on the femoral neck T-score using World Health Organization criteria. Broadband ultrasound attenuation (BUA) at the calcaneus was measured by QUS. The concordance between BUA and BMD was analyzed by the linear regression model.ResultsIn all individuals, BUA modestly correlated with femoral neck BMD (r = 0.35; P ConclusionsIn this population-based study, QUS BUA modestly correlated with DXA BMD, suggesting that BUA is not a reliable method for screening of osteoporosis.

Body composition parameters are linked to cardio-metabolic risk. However, high-quality reference values of body composition are scarce, particularly in Asian population. The aim of study was to construct sex- and age-specific normative reference values of body composition for the Vietnamese population. This study was designed as a cross-sectional investigation that involved 2700 women and 1459 men aged between 20 and 90 (average 48, SD 15) who were participants in the population-based Vietnam Osteoporosis Study. Whole-body composition parameters (e.g., fat mass and lean mass) and site-specific (head, arms, trunk, and legs) parameters were measured by dual-energy X-ray absorptiometry (Hologic Horizon). Reference curves for each parameter and anatomical site were constructed using the Generalized Additive Model for Location Scale and Shape modeling technique. Overall, 8% of women and 11% of men were classified as obese (body mass index ≥ 27.5 kg/m2). Most fat mass was deposited at the trunk (~50%), followed by the leg (~33%). Women had ~10% more body fat (relative to body weight) than men. However, whole-body lean mass was higher in men than women, with the average difference being ~13 kg. Moreover, men had more bone mineral content than women (2110 vs. 1600 g). We also provided a comparison of age-related changes in body composition parameters between Vietnamese and US Whites. These data provide gender- and age-specific reference values of body composition parameters for Vietnamese population. These normative values provide health professionals and the public with a resource for interpretation of body composition data.

Publisher's version (útgefin grein)., Bone area is one measure of bone size that is easily derived from dual-energy X-ray absorptiometry (DXA) scans. In a GWA study of DXA bone area of the hip and lumbar spine (N ≥ 28,954), we find thirteen independent association signals at twelve loci that replicate in samples of European and East Asian descent (N = 13,608 – 21,277). Eight DXA area loci associate with osteoarthritis, including rs143384 in GDF5 and a missense variant in COL11A1 (rs3753841). The strongest DXA area association is with rs11614913[T] in the microRNA MIR196A2 gene that associates with lumbar spine area (P = 2.3 × 10−42, β = −0.090) and confers risk of hip fracture (P = 1.0 × 10−8, OR = 1.11). We demonstrate that the risk allele is less efficient in repressing miR-196a-5p target genes. We also show that the DXA area measure contributes to the risk of hip fracture independent of bone density., We thank all the study subjects for their valuable participation, the staff from all studies and the participating physicians. A part of this research has been conducted using the UK Biobank Resource under Application Number 23359. arcOGEN (http://www.arcogen.org.uk/) was funded by a special purpose grant from Arthritis Research UK (grant 18030).

BackgroundLittle is known about the recent trends in colorectal cancer (CRC) in Vietnam.MethodsBased on the Ho Chi Minh City Cancer Registry data during 1996-2015, we calculated the annual rate of change (ARC) using Joinpoint regression analysis and performed the age-period-cohort (APC) analysis using the United States National Cancer Institute’s web-based statistical tool.ResultsDuring 1996-2015, the overall age-standardized incidence rate of CRC increased from 10.5 to 17.9 per 100,000. CRC incidence elevated more rapidly in men (ARC = 4.7, 95% CI: 2.2–7.3) than women (ARC = 2.6, 95% CI: 0.6–4.8). The highest and lowest increasing ASR observed in the 50-64 years old group (ARC = 5.3, 95% CI: 2.8–7.9) and ConclusionsThe CRC incidence in Ho Chi Minh City increased with the more prominent rising rates among men, older people, and rectal subsites. This study’s result implied the need of launching a population-based CRC screening program in Ho Chi Minh City.

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.

ObjectivesThe association between body composition parameters and peak bone mineral density is not well documented. The aim of this study is to assess the relative contributions of lean mass and fat mass on peak bone mineral density (BMD).MethodsThe study involved 416 women and 334 men aged between 20 and 30 years who were participants in the population-based Vietnam Osteoporosis Study. Whole body composition parameters (eg, fat mass and lean mass) and BMD at the lumbar spine and femoral neck were measured by dual-energy X-ray absorptiometry. The association between lean mass and fat mass and BMD was analyzed by the linear regression model using the Least Absolute Shrinkage and Selection Operator (LASSO).ResultsPeak BMD in men was higher than women, and the difference was more pronounced at the femoral neck (average difference: 0.123 g/cm2; 95% confidence interval [CI] 0.105-0.141 g/cm2) than at the lumbar spine (average difference 0.019 g/cm2; 95% CI, 0.005-0.036 g/cm2). Results of LASSO regression indicated that lean mass was the only predictor of BMD for either men or women. Each kilogram increase in lean mass was associated with ∼0.01 g/cm2 increase in BMD. Lean mass alone explained 16% and 36% of variation in lumbar spine and femoral neck BMD, respectively.ConclusionsLean mass, not fat mass, is the main determinant of peak bone mineral density. This finding implies that good physical activity during adulthood can contribute to the maximization of peak bone mass during adulthood.

Many developing countries, including Vietnam, lack DXA resources for the diagnosis of osteoporosis, which poses difficulties in the treatment and prevention of osteoporosis at the individual level. We have developed and validated a prediction model for individualized assessment of osteoporosis based on age and body weight for men and women. To estimate the prevalence of osteoporosis and to develop and validate a prediction model for estimating the absolute risk of osteoporosis in the Vietnamese population. The study involved 1477 women and 669 men aged 50 years and older, who were recruited from the general population in Ho Chi Minh City (Vietnam). Bone mineral density (BMD) at the femoral neck, total hip, and lumbar spine was measured by DXA (Hologic Horizon). The diagnosis of osteoporosis was based on BMD T-score (T-score ≤ − 2.5) at the femoral neck or lumbar spine which was derived from a published reference range for the Vietnamese population. The logistic regression model was used to develop the prediction model for men and women separately. The bootstrap method was used to evaluate the model performance using 3 indices: the area under the receiver’s operating characteristic curve (AUC), Brier score, and R-squared values. The prevalence of osteoporosis at any site was 28.3% in women and 15.5% in men. The best predictors of osteoporosis risk were age and body weight. Using these indices, a cut-off of 0.195 for women yielded an AUC of 0.825, Brier score = 0.112, and it explained 33.8% of total variance in risk of osteoporosis between individuals. Similarly, in men, the internal validation with a cut-off of 0.09 yielded good accuracy, with AUC = 0.858, Brier score = 0.040, and R-squared = 30.3%. We have developed and validated a prediction model for individualized assessment of osteoporosis. In settings without DXA, this model can serve as a useful screening tool to identify high-risk individuals for DXA scan.

Body composition parameters are linked to cardio-metabolic risk. However, high-quality reference values of body composition are scarce, particularly in Asian population. The aim of study was to construct sex- and age-specific normative reference values of body composition for the Vietnamese population.This study was designed as a cross-sectional investigation that involved 2700 women and 1459 men aged between 20 and 90 (average 48, SD 15) who were participants in the population-based Vietnam Osteoporosis Study. Whole-body composition parameters (e.g., fat mass and lean mass) and site-specific (head, arms, trunk, and legs) parameters were measured by dual-energy X-ray absorptiometry (Hologic Horizon). Reference curves for each parameter and anatomical site were constructed using the Generalized Additive Model for Location Scale and Shape modeling technique.Overall, 8% of women and 11% of men were classified as obese (body mass index ≥ 27.5 kg/mThese data provide gender- and age-specific reference values of body composition parameters for Vietnamese population. These normative values provide health professionals and the public with a resource for interpretation of body composition data.

Background and Aims: The burden of breast cancer in Vietnam has not been documented. This study sought to estimate the incidence of breast cancer in Ho Chi Minh City, the largest economic center of Vietnam, from 1996 to 2015.Methods: This was a population-based study using the Ho Chi Minh City Cancer Registry as a source of data (coverage period: 1996 - 2015). The Registry adopted the International Classification of Diseases for Oncology, 3rd Edition for the classification of primary sites and morphology, and guidelines from the International Agency for Research on Cancer and the International Association of Cancer Registries. Using the population statistics from census data of Ho Chi Minh City, the point incidence of breast cancer for each 5-year period was estimated. Based on the national population, we calculated the age-standardized rate (ASR) of breast cancer between 1996 and 2015.Results: Overall 14,222 new cases of breast cancer (13,498 women, or 95%) had been registered during the 1996-2015 period; among whom, just over half (52%) were in the 2nd stage, and 26% in the 3rd and and 4th stages. In women, the median age at diagnosis was 50 years and there was a slight increase over time. The age-standardized incidence rate of breast cancer during 2011-2015 period was 21.5 cases per 100,000 women, representing an increase of 70% compared to the rate in 1996-2000 period. In men, there was also a significant increase in the age-standardized incidence rate: from 0.22 during the 1996-2001 period to 0.46 per 100,000 men during the 2011-2015 period.Conclusions: These very first data from Vietnam suggest that although the incidence of breast cancer in Vietnam remains relatively low, it has increased over time, and that the increase was mainly attributable to those age groups of 50 and 70.

The present cross-sectional study constructed reference ranges for bone resorption marker beta isomerized form of C-terminal crosslinking telopeptides of type I collagen (beta-CTX) and bone formation marker procollagen type 1 N-terminal propeptide (PINP) for the Vietnamese population. We have further shown that for a given age and weight, higher levels of beta-CTX were significantly associated with bone mineral density in men and women.Normal bone is constantly renewed by two opposing processes of resorption and formation which can be reflected by bone turnover markers (BTMs). This study sought to define the contribution of BTMs to the variation in bone mineral density (BMD) in normal individuals.The study involved 205 men and 432 women aged between 18 and 87, who were randomly selected from various districts within Ho Chi Minh City, Vietnam. Fasting serum levels of PINP and beta-CTX were determined by electrochemiluminescence (Roche, ECLIA). BMD at the lumbar spine (LS) and femoral neck (FN) was measured by dual-energy x-ray absorptiometry (Hologic, Waltham, MA, USA).Among those aged 50 years, women had lower PINP and beta-CTX levels than men, but among those aged 50 years, women had higher PINP and beta-CTX levels than men. In the multiple linear regression analysis, beta-CTX-but not PINP-was significantly associated with both femoral neck (P = 0.008) and lumbar spine BMD (P = 0.008) and the association was independent of gender, age, and body weight. The proportion of variance in BMD attributable to beta-CTX was 1% for femoral neck BMD and 2% for lumbar spine BMD.The elevation in bone formation marker PINP and bone resorption marker beta-CTX in postmenopausal women was greater than in elderly men. However, only beta-CTX was modestly but significantly associated with BMD.

This study sought to define the sex-difference in trabecular and cortical bone parameters in Vietnamese individuals. The study involved 1404 women and 864 men aged between 20 and 86 years who were recruited from Ho Chi Minh City, Vietnam. Trabecular and cortical volumetric BMD were measured at the proximal tibia and proximal radius at 4%, 38%, and 66% points, using a peripheral quantitative computed tomography XCT2000 (Stratec, Germany). Polar strength strain index was estimated from cortical bone parameters. Changes in bone parameters were assessed by the multiple linear regression model. Among individuals aged 20–39 years, women had significantly lower peak trabecular BMD at both the radius (40%) and tibia (16%) than men, but the age-related reduction in trabecular BMD were similar between two sexes. For cortical BMD, peak values in women and men were comparable, but the age-related diminution was greater in women than men. At any age, polar strength strain index in women was lower than men, and the difference was mainly attributable to cortical bone area and total bone mass. We conclude that in the elderly, sex-related difference in trabecular BMD is originated during growth, but sex-related difference in cortical BMD is determined by differential age-related bone loss.

Purpose To estimate the proportion of men and women aged 50 years and older who would be classified as "high risk" for fracture and eligible for anti-fracture treatment. Methods The study involved 1421 women and 652 men aged 50 years and older, who were recruited from the general population in Ho Chi Minh City, Vietnam. Fracture history was ascertained from each individual. Bone mineral density (BMD) was measured at the lumbar spine and femoral neck by DXA (Hologic Horizon). The diagnosis of osteoporosis was based on the T-scores ≤ -2.50 derived from either femoral neck or lumbar spine BMD. The 10-year risks of major fractureand hip fracture were estimated from FRAX version for Thai population. The criteria for recommended treatment were based on the US National Osteoporosis Foundation (NOF). Results The average age of women and men was ~60 yr (SD 7.8). Approximately 11% (n = 152) of women and 14% (n = 92) of men had a prior fracture. The prevalence of osteoporosis was 27% (n = 381; 95% CI, 25 to 29%) in women and 13% (n = 87; 95% CI, 11 to 16%) in men. Only 1% (n = 11) of women and 0.1% (n = 1) of men had 10-year risk of major fracture ≥ 20%. However, 23% (n = 327) of women and 9.5% (n = 62) of men had 10-year risk of hip fracture ≥ 3%. Using the NOF recommended criteria, 49% (n = 702; 95% CI, 47 to 52%) of women and 35% (n = 228; 95% CI, 31 to 39%) of men would be eligible for therapy. Conclusion Almost half of women and just over one-third of men aged 50 years and older in Vietnam meet the NOF criteria for osteoporosis treatment. This finding can help develop guidelines for osteoporosis treatment in Vietnam.

ObjectivesOsteoporosis and fracture impose a significant health care burden on the contemporary populations in developing countries. The Vietnam Osteoporosis Study (VOS) sought to assess the burden of osteoporosis and its comorbidities in men and women.MethodsThe study was designed as a population-based family investigation in which families were randomly recruited from Ho Chi Minh City, Vietnam. Individuals were assessed for bone health, including bone mineral density (BMD) and body composition and trabecular and cortical bone properties by pQCT (peripheral quantitative computed tomography). Fasting blood samples were obtained for the analysis of plasma glucose, glycosylated hemoglobin, and bone turnover markers. Genomic DNA extraction from whole blood samples for further genetic and genomic analyses.ResultsWe have recruited more than 4157 individuals from 817 families. The average age of participants was 51, with approximately 45% of the individuals aged 50 years and older. Approximately 3% of participants were obese (body mass index ≥ 30 kg/m2), and 21% were overweight. Notably, 11% of participants aged 40 years and older were diabetic. Among those aged 50 years and older, approximately 14% of women and 5% of men had osteoporosis (i.e., femoral neck BMD T-scores ≤ -2.5). There were modest correlations between volumetric BMD and areal BMD.ConclusionsVOS is a major bone research project in Vietnam aimed at comprehensively documenting the burden osteoporosis, its co-occurrence of chronic diseases, and their underlying etiologies. The Study will make important contributions to the literature of bone health worldwide.

ObjectivesThe association between osteoporosis and atherosclerosis remains controversial. We sought to define the relationship between carotid intima-media thickness and bone mineral density (BMD) in individuals of Vietnamese background.Design and settingCross-sectional study in Ho Chi Minh City, Vietnam.ParticipantsThe study involved 1460 individuals (559 men) aged 50 years and older (average age 59 years) who were randomly recruited from the community.Outcome measuresBMD at the femoral neck and lumbar spine was measured by dual-energy X-ray absorptiometry (Hologic, Waltham, Massachusetts, USA). Carotid intima-media thickness (cIMT) was measured using a Philips Ultrasonography (HD7XE). The presence of atherosclerotic plaque was ascertained for each individual. The association between cIMT and BMD was analysed by a multiple linear regression model.ResultsIn unadjusted analysis, cIMT was positively associated with femoral neck BMD in men (p=0.005), but not in women (p=0.242). After adjusting for age, smoking, diabetes and hypertension, the association remained statistically significant in men (partial R2=0.005; p=0.015) but not in women (partial R2=0.008; p=0.369). When the analysis was limited to individuals aged 60 years and older, the association between cIMT and BMD was no longer statistically significant. There was no statistically significant association between cIMT and lumbar spine BMD in either men or women.ConclusionsIn Vietnamese individuals aged 50 years and older, there is a clinically non-significant but statistically significant association between carotid intima-media thickness and BMD in men, not in women.

© 2019 Aims: Trabecular bone score (TBS) is a surrogate indicator of bone microarchitecture. The present study sought to examine the association between type 2 diabetes (T2D) and trabecular bone score (TBS) in adult Vietnamese men and women. Methods: The study was part of the Vietnam Osteoporosis Study, in which 2702 women and 1398 men aged ≥30 years were recruited from the general community in Ho Chi Minh City. HbA1c levels were measured by the ADAMS™ A1c HA-8160 (Arkray, Kyoto, Japan), and classified into 3 groups: normal if HbA1c < 5.7%; pre-diabetes (5.7–6.4%); and diabetes (>6.4%). TBS was evaluated by iNsight Software, version 2.1 (Medimaps, Merignac, France) on lumbar spine BMD scan (Hologic Horizon). Differences in TBS between diabetic status were analyzed by the multivariable regression model with adjustment for age and body mass index. Results: The prevalence of pre-diabetes and diabetes in men and women was 30.2% and 8.3%, respectively. In women, TBS was lower in pre-diabetes (−0.02; P < 0.001) and diabetes (−0.02; P < 0.001) compared with normal individuals. In men, there was no statistically significant difference in TBS between diabetic status. Moreover, TBS was significantly inversely correlated with HbA1c levels in women (P = 0.01), but not in men (P = 0.89). Conclusion: Women, but not men, with type 2 diabetes and pre-diabetes have lower TBS than individuals without diabetes. These data suggest that diabetes and prediabetes are associated with deterioration of bone microarchitecture.

© 2019, International Osteoporosis Foundation and National Osteoporosis Foundation. Summary: Patients with type 2 diabetes have an increased risk of fracture despite having a higher areal bone mineral density. This meta-analysis showed that compared with controls, diabetic patients had a lower trabecular bone score (TBS) than non-diabetic individuals, suggesting that TBS can be a useful measurement for the assessment of fracture risk in diabetic patients. Introduction: The association between type 2 diabetes and trabecular bone score (TBS) has not been clear. The present study sought to answer the specific question of whether patients with type 2 diabetes have a lower TBS than those without diabetes. Methods: Using electronic and manual search, we identified 12 studies that had examined the association between type 2 diabetes and TBS between 2013 and 2019. These studies involved 35,546 women and 4962 men aged 30 years and older. We extracted the mean and standard deviation of TBS for patients with and without diabetes. The synthesis of effect sizes was done by the random effects meta-analysis model. Results: Patients with diabetes had significantly lower TBS than those without diabetes, with standardized mean difference being − 0.31 (95% CI, − 0.45 to − 0.16). The difference was greater in women (− 0.50; 95% CI, − 0.69 to − 0.32) than in men (− 0.04; 95% CI, − 0.17 to 0.10). Compared with normal individuals, those with prediabetes had significantly lower TBS (d = − 0.13; 95% CI, − 0.23 to − 0.04; P = 0.005). There was heterogeneity between the studies, with the index of inconsistency (I2) ranging from 92% (in women) to 69.5% (in men). Conclusion: Patients with type 2 diabetes have a lower TBS than non-diabetic individuals, suggesting that TBS can be a useful measurement for the assessment of fracture risk in diabetic patients.

This study sought to estimate the extent of genetic influence on the variation in trabecular bone score (TBS). We found that genetic factors accounted for ~45% of variance in TBS, and that the co-variation between TBS and bone density is partially determined by genetic factors.Trabecular bone score has emerged as an important predictor of fragility fracture, but factors underlying the individual differences in TBS have not been explored. In this study, we sought to determine the genetic contribution to the variation of TBS in the general population.The study included 556 women and 189 men from 265 families. The individuals aged 53years (SD 11). We measured lumbar spine bone mineral density (BMD; Hologic Horizon) and then derived the TBS from the same Hologic scan where BMD was derived. A biometric model was applied to the data to partition the variance of TBS into two components: one due to additive genetic factors, and one due to environmental factors. The index of heritability was estimated as the ratio of genetic variance to total variance of a trait. Bivariate genetic analysis was conducted to estimate the genetic correlation between TBS and BMD measurements.TBS was strongly correlated with lumbar spine BMD (r=0.73; P0.001). On average TBS in men was higher than women, after adjusting age and height which are significantly associated with both TBS and lumbar spine BMD. The age and height adjusted index of heritability of TBS was 0.46 (95% CI, 0.39-0.54), which was not much different from that of LSBMD (0.44; 95% CI, 0.31-0.55). Moreover, the genetic correlation between TBS and LSBMD was 0.35 (95% CI, 0.21-0.46), between TBS and femoral neck BMD was 0.21 (95% CI, 0.10-0.33).Approximately 45% of the variance in TBS is under genetic influence, and this effect magnitude is similar to that of lumbar spine BMD. This finding provides a scientific justification for the search for specific genetic variants that may be associated with TBS and fracture risk.

To test the hypothesis that the relationship between fat mass (FM) and bone mineral density (BMD) is mediated by leptin. The study involved 611 individuals aged 20-89 years who were randomly sampled from Ho Chi Minh City (Vietnam). BMD at the femoral neck (FN), lumbar spine (LS), and whole body (WB) was measured by DXA. Lean mass and FM were derived from the WB DXA scan. Leptin was measured by ELISA (DRG Diagnostics, Germany). The regression method was used to partition the variance of leptin and FM on BMD. The mediated effect of leptin was analyzed by the mediation analysis model. In the multiple linear regression, leptin, FM, and age collectively accounted for ~34 % variation in FNBMD in men and women. However, only 0.5 % of this explained variance was due to leptin. Of the total effect of FM on FNBMD, the mediated effect of leptin accounted for 6.1 % (P = 0.38) in men and 7.1 % (P = 0.99) in women. The same trend was observed for LS and WBBMD. These data suggest that greater FM is associated with greater BMD, but the association is not mediated by leptin, and that leptin has a non-significant influence on bone mass.

© 2018, International Osteoporosis Foundation and National Osteoporosis Foundation. Summary: It is not clear why type 2 diabetes (T2D) has an increased risk of fracture despite higher areal bone mineral density. This study showed that compared with controls, T2D patients had higher trabecular bone density but lower cortical bone density, resulting in a lower bone strength. Introduction: To define the association between type 2 diabetes and bone architecture and measures of bone strength. Methods: The study was part of the Vietnam Osteoporosis Study, in which 1115 women and 614 men aged ≥ 30 were randomly recruited from Ho Chi Minh City. HbA1c levels were measured with analyzers ADAMS™ A1c HA-8160 (Arkray, Kyoto, Japan). The diagnosis of T2D was made if HbA1c was ≥ 6.5%. Trabecular and cortical volumetric bone density (vBMD) was measured in the forearm and leg by a pQCT XCT2000 (Stratec, Germany). Polar stress strain index (pSSI) was derived from the pQCT measurements. Difference in bone parameters between T2D and non-diabetic individuals was assessed by the number of standard deviations (effect size [ES]) by the propensity score analysis. Results: The prevalence of T2D was ~ 8%. The results of propensity score matching for age, sex, and body mass index in 137 pairs of diabetic and non-diabetic individuals showed that T2D patients had significantly higher distal radius trabecular vBMD (ES 0.26; 95% CI, 0.02 to 0.50), but lower cortical vBMD (ES − 0.22; − 0.46 to 0.00) and reduced pSSI (ES − 0.23; − 0.47 to − 0.02) compared with non-diabetic individuals. Multiple linear regression analysis based on the entire sample confirmed the results of the propensity score analysis. Conclusion: Compared with non-diabetic individuals, patients with T2D have greater trabecular but lower cortical vBMD which leads to lower bone strength.

The original HTML version of this Article was updated shortly after publication to add links to the Peer Review file.In addition, affiliations 16 and 17 incorrectly read ‘School of Medicine Sydney, University of Notre Dame Australia, Sydney, WA, 6160, Australia’ and ‘St Vincent’s Clinical School, University of New South Wales Medicine, University of New South Wales, Sydney, NSW, 2052, Australia.’ This has now been corrected in both the PDF and HTML versions of the Article.

Greater body mass index (BMI) is associated with a greater risk of osteoarthritis (OA). This study sought to investigate whether the association is mediated by fat mass or lean mass. The study involved 170 men and 488 women aged between 20 and 90 (average age: 55) who were randomly recruited from Ho Chi Minh City, Vietnam. The presence of knee OA was radiographically diagnosed based on the Kellgren-Lawrence criteria. Lean mass (LM) and fat mass (FM) were obtained from the DXA whole body scan (Hologic QDR-4500). The relationship between OA, LM, and FM was analyzed by a series of multiple linear regression models which take into account the effects of gender and age. As expected, men and women with knee OA were older than those without OA (65 vs 51 year in men, and 64 vs 52 year in women). After adjusting for age, OA was associated with greater FM and percent body fat (PBF), but the association was only observed in women, not in men. There was no statistically significant difference in LM between OA and non-OA individuals. Moreover, after adjusting for age and BMI or PBF, bone density in OA patients was not significantly different from non-OA individuals. Women with OA of the knee have greater fat mass than non-OA individuals, and that there is no significant difference in bone density between OA and non-OA individuals. Thus, the association between body mass index and OA is mainly mediated by fat mass.

Background and aim Bone mineral density (BMD) is under strong genetic regulation, but it is not clear which genes are involved in the regulation, particularly in Asian populations. This study sought to determine the association between 29 genes discovered by Caucasian-based genome-wide association studies and BMD in a Vietnamese population. Methods The study involved 564 Vietnamese men and women aged 18 years and over (average age: 47 years) who were randomly sampled from the Ho Chi Minh City. BMD at the femoral neck, lumbar spine, total hip and whole body was measured by DXA (Hologic QDR4500, Bedford, MA, USA). Thirty-two single nucleotide polymorphisms (SNPs) in 29 genes were genotyped using Sequenom MassARRAY technology. The magnitude of association between SNPs and BMD was analyzed by the linear regression model. The Bayesian model average method was used to identify SNPs that are independently associated with BMD. Results The distribution of genotypes of all, but two, SNPs was consistent with the Hardy–Weinberg equilibrium law. After adjusting for age, gender and weight, 3 SNPs were associated with BMD: rs2016266 (SP7 gene), rs7543680 (ZBTB40 gene), and rs1373004 (MBL2/DKK1 gene). Among the three genetic variants, the SNP rs2016266 had the strongest association, with each minor allele being associated with ~ 0.02 g/cm2 increase in BMD at the femoral neck and whole body. Each of these genetic variant explained about 0.2 to 1.1% variance of BMD. All other SNPs were not significantly associated with BMD. Conclusion These results suggest that genetic variants in the SP7, ZBTB40 and MBL2/DKK1 genes are associated with BMD in the Vietnamese population, and that the effect of these genes on BMD is likely to be modest.

© 2017 Ho-Pham et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Objective HbA1c has been introduced as a complementary diagnostic test for diabetes, but its impact on disease prevalence is unknown. This study evaluated the concordance between HbA1c and fasting plasma glucose (FPG) in the diagnosis of diabetes in the general population. Materials and methods The study was designed as a population based investigation, with participants being sampled from the Ho Chi Minh City, Vietnam. Blood samples were collected after overnight fasting and analyzed within 4 hours after collection. HbA1c was measured with high pressure liquid chromatography (Arkray Adams, Japan). FPG was measured by the hexokinase method (Advia Autoanalyzer; Bayer Diagnostics, Germany). Diabetes was defined as HbA1c 6.5% or FPG 7.0 mmol/L. Prediabetes was classified as HbA1c between 5.7% and 6.4%. Results The study included 3523 individuals (2356 women) aged 30 years and above. Based on the HbA1c test, the prevalence of diabetes and prediabetes was 9.7% (95%CI, 8.7–10.7%; n = 342) and 34.6% (33.0–36.2; n = 1219), respectively. Based on the FPG test, the prevalence of diabetes and prediabetes was 6.3% (95%CI, 5.5–7.2%; n = 223) and 12.1% (11.1–13.2; n = 427). Among the 427 individuals identified by FPG as "pre-diabetes", 28.6% were classified as diabetes by HbA1c test. The weighted kappa statistic of concordance between HbA1c and FPG was 0.55, with most of the discordance being in the prediabetes group. Conclusion These data indicate that there is a significant discordance in the diagnosis of diabetes between FPG and HbA1c measurements, and the discordance could have significant impact on clinical practice. FPG appears to underestimate the burden of undiagnosed diabetes.

The Asia Pacific region, with its rapid economic development and changes in lifestyles, has been identified as an epicenter of diabetes. However, the prevalence of diabetes in this region has not been well documented. Glycated hemoglobin (HbA1c) has been introduced as a new diagnostic test for diabetes, but its impact on disease prevalence is unknown. In this study, we sought to estimate the prevalence of undiagnosed diabetes in an urban population in Vietnam by using new HbA1c diagnostic criteria. The study was designed as a population-based investigation that involved 1,339 individuals (973 women) randomly sampled from Ho Chi Minh City, Vietnam. All individuals were aged 30 years and above (average age ∼53 years, no significant difference between women and men). Blood samples were collected after overnight fasting and analyzed within 24 h after collection. HbA1c was measured with high-performance liquid chromatography (ARKRAY, …

Background. Vitamin D deficiency has been shown to be a risk factor for various chronic diseases and mortality. It is not clear why vitamin D deficiency affects a large proportion of individuals living in tropical Asian countries. Objective. The present study sought to examine the knowledge, behavior and attitude of Vietnamese men and women toward vitamin D and sunlight exposure. Methodology. The study was designed as a cross-sectional survey of a population in Ho Chi Minh City, Vietnam. Study participants were randomly drawn from the general community, supermarkets and hospital visitors. Each participant was given a questionnaire relating to knowledge on vitamin D and behavior toward sunlight exposure. The questionnaire was previously tested for reliability and accuracy in 20 participants. Results. A total of 1,536 individuals aged 14 to 85 years participated in the study. Fifty three percent of participants did not like being exposed to sunlight. On the average, most reported approximately 14 hours per week under the sun. Majority (81%) reported that they had heard of vitamin D from newspapers (32%), friends (20%) or radio and television (13%). However, their knowledge about the source of vitamin D was inadequate: 37% thought that vitamin D comes from the sun, 28% from foodstuff and the sun, while 17% did not know the source of vitamin D. Analysis of the determinants of knowledge of vitamin D suggested that only educational level was a significant predictor of vitamin D knowledge. Conclusion. A negative attitude toward sunlight exposure and inadequacy of knowledge on vitamin D could adversely affect bone and general health in the community. The data also provides a basis for developing public health strategies for the prevention of vitamin D deficiency in the Vietnamese population.

Based on quantitative measurements of vertebral heights, the prevalence of undiagnosed vertebral fracture in Vietnamese men and women aged 50 years and older was 23 and 26 %, respectively.The present study sought to develop reference ranges for vertebral heights and to determine the prevalence of asymptomatic vertebral fracture in Vietnamese men and women.The study included 312 men and 657 women aged over 18 who were randomly selected from the community. The ImageJ software program was used to measure anterior height (H(a)), middle height (H(m)), and posterior height (H(p)) for each vertebra (T4 to T12 and L1 to L5). Four vertebral ratios were determined: H(a)/H(p), H(m)/H(p), H(p)/H(p + 1), and H(p)/H(p − 1). Reference ranges for the ratios were then developed by the method of Winsorized mean. Vertebral fracture was diagnosed as a ratio lower than three standard deviations from the normal mean.For any given vertebra, H(a), H(m), and H(p) in men were higher than in women. In both sexes, H(a) and H(m) increased in a stepwise fashion from T4 to L3 and then gradually reduced in L4–L5. Vertebral heights for T4–T9 tended to decrease, while vertebral height for T10–L5 tended to increase with advancing age. Among those aged over 50 years, the prevalence of vertebral fracture in men was 23.3 % (95 % confidence interval (CI) 16.8–31.3 %) which was lower than that in women (26.5 %; 95 % CI 22.4–31.1 %). The prevalence increased with advancing age, such that from the age of over 70, 41 % of men and 42 % women had at least one vertebral fracture.One fourth of Vietnamese men and women aged 50 years and older have a symptomatic vertebral fracture. This prevalence is equivalent to that in Caucasian populations.

The effect of vegan diet on bone loss has not been studied. The aim of this study was to examine the association between veganism and bone loss in postmenopausal women.The study was designed as a prospective longitudinal investigation with 210 women, including 105 vegans and 105 omnivores. Femoral neck (FN) bone mineral density (BMD) was measured in 2008 and 2010 by dual-energy X-ray absorptiometry (Hologic QDR4500). The incidence of vertebral fracture was ascertained by X-ray report. Serum levels of C-terminal telopeptide of type I collagen (βCTX) and N-terminal propeptide of type I procollagen (PINP) were measured by Roche Elecsys assays. Serum concentration of 25-hydroxyvitamin D and parathyroid hormone were measured by electrochemiluminescence.Among the 210 women who initially participated in the study in 2008, 181 women had completed the study and 29 women were lost to follow-up. The rate of loss in FN BMD was -1.91±3.45%/year in omnivores and -0.86±3.81%/year (P=0.08) in vegans. Lower body weight, higher intakes of animal protein and lipid, and corticosteroid use were associated with greater rate of bone loss. The 2-year incidence of fracture was 5.7% (n=5/88) in vegans, which was not significantly different from omnivores (5.4%, n=6/93). There were no significant differences in βCTX and PINP between vegans and omnivores. The prevalence of vitamin D insufficiency in vegans was higher than in omnivores (73% versus 46%; P=0.0003).Vegan diet did not have adverse effect on bone loss and fracture. Corticosteroid use and high intakes of animal protein and animal lipid were negatively associated with bone loss.

Summary: In this cross-sectional study in Vietnam, the prevalence of vitamin D insufficiency was 46% in adult women and 20% in adult men. There was a linear inverse relationship between serum 25(OH)D and PTH concentrations, but there was no threshold of 25(OH)D at which PTH levels plateaued. Introduction: Vitamin D insufficiency is adversely associated with health outcomes. Vitamin D status in Asian populations is not well documented. This study sought to assess vitamin D status and its relationship to parathyroid hormone in a Vietnamese population. Methods: This cross-sectional study involved 205 men and 432 women aged 18-87 years, who were randomly sampled from various districts in Ho Chi Minh City (Vietnam) according to a proportional sampling scheme. Serum concentration of 25(OH)D and PTH were measured by the Electrochemiluminescence immunoassay on the Roche Elecsys 10100/201 system (Roche Diagnosis Elecsys). Vitamin D insufficiency was quantified as serum 25(OH)D levels below 30 ng/ml (75 nmol/L). Results: The average age for men and women was 43.8 ± 18.4 years (mean ± SD) and 47.7 ± 17.1 years, respectively. The mean 25(OH)D concentration in men (36.8 ± 10.2 ng/mL) was significantly higher than in women (30.1 ± 5.9; P < 0.0001). The prevalence of vitamin D insufficiency in men was 20% (41/205) which was significantly lower than in women (46%, 199/432). Age, height and weight were independent predictors of 25(OH)D concentrations, and the three factors explained 15% and 5% of variance in 25(OH)D in men and women, respectively. There was a linear inverse relationship between serum 25(OH)D and PTH concentrations, but there was no threshold of 25(OH)D at which PTH levels plateaued. Conclusions: These data show that vitamin D insufficiency is common even in tropical region, and that women had a greater risk of vitamin D insufficiency than men. These data suggest that an elevation in PTH cannot be used as a marker for vitamin D deficiency. © 2010 International Osteoporosis Foundation and National Osteoporosis Foundation.

It has been widely assumed that for a given BMI, Asians have higher percent body fat (PBF) than whites, and that the BMI threshold for defining obesity in Asians should be lower than the threshold for whites. This study sought to test this assumption by comparing the PBF between US white and Vietnamese women. The study was designed as a comparative cross-sectional investigation. In the first study, 210 Vietnamese women ages between 50 and 85 were randomly selected from various districts in Ho Chi Minh City (Vietnam). In the second study, 419 women of the same age range were randomly selected from the Rancho Bernardo Study (San Diego, CA). In both studies, lean mass (LM) and fat mass (FM) were measured by dual-energy X-ray absorptiometry (DXA) (QDR 4500; Hologic). PBF was derived as FM over body weight. Compared with Vietnamese women, white women had much more FM (24.8 +/- 8.1 kg vs. 18.8 +/- 4.9 kg; P0.0001) and greater PBF (36.4 +/- 6.5% vs. 35.0 +/- 6.2%; P = 0.012). However, there was no significant difference in PBF between the two groups after matching for BMI (35.1 +/- 6.2% vs. 35.0 +/- 5.7%; P = 0.87) or for age and BMI (35.6 +/- 5.1% vs. 35.8 +/- 5.9%; P = 0.79). Using the criteria of BMIor=30, 19% of US white women and 5% of Vietnamese women were classified as obese. Approximately 54% of US white women and 53% of Vietnamese women had their PBF35% (P = 0.80). Although white women had greater BMI, body weight, and FM than Vietnamese women, their PBF was virtually identical. Further research is required to derive a more appropriate BMI threshold for defining obesity for Asian women.

Background Vertebral fracture is associated with an increased risk of atraumatic fracture and mortality. The prevalence of vertebral fractures among postmenopausal Caucasian women has been reported to range between 15% and 35%. Because there is no estimate of the magnitude of the problem in Vietnam, we undertook this study to estimate the prevalence and risk factors of vertebral fracture in Vietnam. Methods Radiographs were taken from 209 postmenopausal women aged between 50 and 85 years (average 62) who were randomly sampled from various districts in Ho Chi Minh City. The presence of vertebral fracture was assessed by the Genant's semi-quantitative method with two independent readers. Bone mineral density (BMD) at the lumbar spine (LS), femoral neck (FN) and whole body was measured by DXA (Hologic QDR4500). Anthropometric and clinical data were obtained by a standardized questionnaire. Results Among the 209 women, 48 were found to have at least one radiographic vertebral fracture, which yielded a prevalence of 23% (95%CI: 18–29%). Although fracture occurred in all vertebrae, most (83%) occurred at the L1–L5. Most fractures occurred at one vertebra, and only 12% occurred at multiple vertebrae. The prevalence increased with age such that it reached 39% among those aged 70+ years. There was no significant association between vertebral fracture and back pain, fall history, and dietary calcium intake. In simple log-binomial regression analysis, higher risk of vertebral fracture was associated with advancing age (prevalence ratio [PR] per 10 years: 1.40; 1.16–2.05) and lower lumbar spine BMD (PR per SD: 1.51; 1.18–1.92). In multivariable analysis, the two factors remained independently associated with fracture risk, with the area under the receiver operating characteristic curve being 0.66. Conclusions These data suggest that approximately one out of 4 postmenopausal women in Vietnam have a radiographic vertebral fracture, and this prevalence is as common as in Caucasian populations. The number of women needed to screen to identify one vertebral fracture is about 4 to 5, which seems to be cost-effective.