Asia-Pacific consensus on long-term and sequential therapy for osteoporosis.

Objectives: This study aimed to present the Asia-Pacific consensus on long-term and sequential therapy for osteoporosis, offering evidence-based recommendations for the effective management of this chronic condition. The primary focus is on achieving optimal fracture prevention through a comprehensive, individualized approach. Methods: A panel of experts convened to develop consensus statements by synthesizing the current literature and leveraging clinical expertise. The review encompassed long-term anti-osteoporosis medication goals, first-line treatments for individuals at very high fracture risk, and the strategic integration of anabolic and antiresorptive agents in sequential therapy approaches. Results: The panelists reached a consensus on 12 statements. Key recommendations included advocating for anabolic agents as the first-line treatment for individuals at very high fracture risk and transitioning to antiresorptive agents following the completion of anabolic therapy. Anabolic therapy remains an option for individuals experiencing new fractures or persistent high fracture risk despite antiresorptive treatment. In cases of inadequate response, the consensus recommended considering a switch to more potent medications. The consensus also addressed the management of medication-related complications, proposing alternatives instead of discontinuation of treatment. Conclusions: This consensus provides a comprehensive, cost-effective strategy for fracture prevention with an emphasis on shared decision-making and the incorporation of country-specific case management systems, such as fracture liaison services. It serves as a valuable guide for healthcare professionals in the Asia-Pacific region, contributing to the ongoing evolution of osteoporosis management.

Development of a shape-based algorithm for identification of asymptomatic vertebral compression fractures: A proof-of-principle study.

Objectives: Vertebral fracture is both common and serious among adults, yet it often goes undiagnosed. This study aimed to develop a shape-based algorithm (SBA) for the automatic identification of vertebral fractures. Methods: The study included 144 participants (50 individuals with a fracture and 94 without a fracture) whose plain thoracolumbar spine X-rays 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 determine the 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 person and vertebra levels. Results: At the person level, the SBA achieved a sensitivity of 100% and specificity of 62% (95% CI, 51%-72%). At the vertebra level, the SBA achieved a sensitivity of 84% (95% CI, 72%-93%), and a specificity of 88% (95% CI, 85%-90%). On average, the SBA took 0.3 s to assess each 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.

Prevalence, incidence of and risk factors for vertebral fracture in the community: the Vietnam Osteoporosis Study.

The epidemiology of vertebral fractures (VF) in underrepresented populations is not well-documented. This cohort study was part of a longitudinal osteoporosis research project with the aim of determining the prevalence, incidence, and risk factors for VF. 401 individuals (155 men) aged 50 years and older without a clinical diagnosis of VF were took radiographs at baseline and 2 years later. VF were ascertained using the Genant's semi-quantitative method. Bone mineral density (BMD) of femoral neck and lumbar spine were measured by dual-energy X-ray absorptiometry (Hologic Inc). The association between VF and risk factors was analyzed by the multiple logistic regression. The 95% confidence interval for prevalence and incidence was estimated by exact Poisson test. At baseline, the prevalence of VF was 12.2% (n = 49, 95% CI 9.0-16.2%) and increased with advancing age with one-fifth of those aged 70 and older having a VF. During the follow-up period, we observed 6 new VF, making the incidence of 6.6/1000 person-years (n = 6, 95% CI 2.4-14.3). The risk of prevalent VF was associated with male gender (OR: 2.67; 95% CI 1.28-5.87) and T-score at the femoral neck (OR per one SD decrease: 1.1; 1.03-1.17). These data indicate that VF is common among adults, and that lower femoral neck BMD was a risk factor for VF.

Machine learning to detect the SINEs of cancer.

We previously described an approach called RealSeqS to evaluate aneuploidy in plasma cell-free DNA through the amplification of ~350,000 repeated elements with a single primer. We hypothesized that an unbiased evaluation of the large amount of sequencing data obtained with RealSeqS might reveal other differences between plasma samples from patients with and without cancer. This hypothesis was tested through the development of a machine learning approach called Alu Profile Learning Using Sequencing (A-PLUS) and its application to 7615 samples from 5178 individuals, 2073 with solid cancer and the remainder without cancer. Samples from patients with cancer and controls were prespecified into four cohorts used for model training, analyte integration, and threshold determination, validation, and reproducibility. A-PLUS alone provided a sensitivity of 40.5% across 11 different cancer types in the validation cohort, at a specificity of 98.5%. Combining A-PLUS with aneuploidy and eight common protein biomarkers detected 51% of the cancers at 98.9% specificity. We found that part of the power of A-PLUS could be ascribed to a single feature-the global reduction of AluS subfamily elements in the circulating DNA of patients with solid cancer. We confirmed this reduction through the analysis of another independent dataset obtained with a different approach (whole-genome sequencing). The evaluation of Alu elements may therefore have the potential to enhance the performance of several methods designed for the earlier detection of cancer.

Prevalence of and risk factors for sarcopenia in community-dwelling people: The Vietnam Osteoporosis Study.

BACKGROUND: Sarcopenia is a geriatric disease characterized by the progressive and generalized loss of skeletal lean mass and strength with age. The prevalence of sarcopenia in the Vietnamese population is unknown. This study sought to estimate the prevalence of and risk factors for sarcopenia among community-dwelling individuals in Vietnam. METHODS: This cross-sectional study is part of the ongoing Vietnam Osteoporosis Study project. The study involved 1308 women and 591 men aged 50 years and older as at 2015 (study entry). Whole-body dual-energy X-ray absorptiometry was used to measure the appendicular skeletal lean mass. Anthropometric and clinical data were collected using a structured questionnaire. Sarcopenia was defined according to the criteria proposed by the Asian Working Group for Sarcopenia in 2019. Logistic regression analysis was used to determine the association between potential risk factors and sarcopenia. RESULTS: The prevalence of sarcopenia in women and men was 14% (n = 183) and 16% (n = 83), respectively. Age (odds ratio [OR] per 10 years = 1.37; 95% confidence interval [CI] 1.26-1.48) and being underweight (OR = 1.61; 95% CI 1.00-2.58) were independently associated with increased risk of sarcopenia. The combination of low physical activity, being underweight and advancing age accounted for ~27% of sarcopenic patients. However, most of the attributable fraction was due to ageing. CONCLUSIONS: Sarcopenia is common in community-dwelling Vietnamese adults, particularly those with advancing age, who are underweight and with low physical activity.

Longitudinal changes in bone mineral density during perimenopausal transition: the Vietnam Osteoporosis Study.

Based on the prospective cohort of the Vietnam Osteoporosis Study, we show that bone loss occurred before menopause, and that the loss accelerated in the first 5 years post-menopause. PURPOSE: To define the change in bone mineral density (BMD) among women during the menopausal transition. METHODS: The study involved 1062 women aged 40-59 who were participants of the population-based prospective Vietnam Osteoporosis Study. BMD at the femoral neck (FN), lumbar spine (LS), and whole body scan was measured by DXA. Each woman has had two BMD measurements separated by approximately 2 years, and the rate of BMD change was calculated for each woman. Multivariable linear regression models were used to quantify the association between body composition parameters and the rate of BMD change. RESULTS: At FN, there were 3 phases of BMD change: a slight decline before the age of 45-49 (average loss of 0.51%/year); a substantial decline between the ages of 49 and 54 (average loss of 1.39%/year); and then slowed down between the ages of 54 and 59 (average loss of 0.31%/year). The same trend was also observed at LS: a slight decline (- 0.56%/year) among women aged 45-49; then a significant decline between the ages of 50 and 54 (- 1.33%/year); but then slowed down at - 0.31%/year after the age of 55. Changes in BMD were not significantly associated with changes in lean mass or fat mass. CONCLUSIONS: Although bone loss occurred before menopause, the loss accelerated in the early perimenopausal transition (45-50 years of age). This finding suggests that screening for osteoporosis in women should be considered at the age of 45.

Detection of rare mutations, copy number alterations, and methylation in the same template DNA molecules.

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.

Trends in colorectal cancer incidence in Ho Chi Minh City, Vietnam (1996-2015): Joinpoint regression and age-period-cohort analyses.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Mechanography assessment of fall risk in older adults: the Vietnam Osteoporosis Study.

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.

Burden of osteoporosis in Vietnam: An analysis of population risk.

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.

Discordance between quantitative ultrasound and dual-energy X-ray absorptiometry in bone mineral density: The Vietnam Osteoporosis Study.

OBJECTIVES: Calcaneal 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. METHODS: The 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. RESULTS: In all individuals, BUA modestly correlated with femoral neck BMD (r = 0.35; P < 0.0001) and lumbar spine BMD (r = 0.34; P < 0.0001) in both men and women. In individuals aged 50 years and older, approximately 16% (n = 92/575) of women and 3.2% (n = 10/314) of men were diagnosed to have osteoporosis. Only 0.9% (n = 5/575) women and 1.0% (n = 3/314) men were classified as "Low BUA". The kappa coefficient of concordance between BMD and BUA classification was 0.09 (95% CI, 0.04 to 0.15) for women and 0.12 (95% CI, 0.03 to 0.22) for men. CONCLUSIONS: In this population-based study, QUS BUA modestly correlated with DXA BMD, suggesting that BUA is not a reliable method for screening of osteoporosis.

Trends in incidence and histological pattern of thyroid cancer in Ho Chi Minh City, Vietnam (1996-2015): a population-based study.

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 < 45 years age group was the highest diagnosed overall and increased significantly in both men (APC 11.0) and women (APC 10.1). Both genders shared similar distribution of subtype incidences, with papillary thyroid cancer constituted the most diagnosed (73.3% in men and 85.2% in women). The papillary thyroid cancer observed a markedly increase overall (APC of 10.7 (95% CI 9.3-12.0)). 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.

Trends in breast cancer incidence in Ho Chi Minh City 1996-2015: A registry-based study.

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. 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 5-year period was estimated. Based on the national population, we calculated the age-standardized rate (ASR) of breast cancer between 1996 and 2015. Overall 14,222 new cases of breast cancer (13,948 women, or 98%) 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 4th stages. In women, the median age at diagnosis was 50 years and there was a slight increase over time. The ASR of breast cancer during the 2011-2015 period was 107.4 cases per 100,000 women, representing an increase of 70% compared to the rate during the 1996-2000 period. In men, there was also a significant increase in the ASR: from 1.13 during the 1996-2001 period to 2.32 per 100,000 men during the 2011-2015 period. These very first data from Vietnam suggest that although the incidence of breast cancer in Vietnam remains relatively low, it has increased over time.

Reference values of body composition parameters for Vietnamese men and women.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Development of a model for identification of individuals with high risk of osteoporosis.

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. PURPOSE: 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. METHODS: 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. RESULTS: 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%. CONCLUSION: 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.

Lean mass and peak bone mineral density.

OBJECTIVES: The 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). METHODS: The 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). RESULTS: Peak 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. CONCLUSIONS: Lean 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.

Association between carotid intima-media thickness and bone mineral density: a cross-sectional study in Vietnamese men and women aged 50 years and older.

OBJECTIVES: The 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 SETTING: Cross-sectional study in Ho Chi Minh City, Vietnam. PARTICIPANTS: The study involved 1460 individuals (559 men) aged 50 years and older (average age 59 years) who were randomly recruited from the community. OUTCOME MEASURES: BMD 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. RESULTS: In 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. CONCLUSIONS: In 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.

Association between pre-diabetes, type 2 diabetes and trabecular bone score: The Vietnam Osteoporosis Study.

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.

Publisher Correction: GWAS of bone size yields twelve loci that also affect height, BMD, osteoarthritis or fractures.

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.

GWAS of bone size yields twelve loci that also affect height, BMD, osteoarthritis or fractures.

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, ß = -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.