BONEcheck: A digital tool for personalized bone health assessment.

Objectives: Osteoporotic fracture is a significant public health burden associated with increased mortality risk and substantial healthcare costs. Accurate and early identification of high-risk individuals and mitigation of their risks is a core part of the treatment and prevention of fractures. Here we introduce a digital tool called 'BONEcheck' for personalized assessment of bone health. Methods: The development of BONEcheck primarily utilized data from the prospective population-based Dubbo Osteoporosis Epidemiology Study and the Danish Nationwide Registry. BONEcheck has 3 modules: input data, risk estimates, and risk context. Input variables include age, gender, prior fracture, fall incidence, bone mineral density (BMD), comorbidities, and genetic variants associated with BMD. Results: Based on the input variables, BONEcheck estimates the probability of any fragility fracture and hip fracture within 5 years, subsequent fracture risk, skeletal age, and time to reach osteoporosis. The probability of fracture is shown in both numeric and human icon array formats. The risk is also contextualized within the framework of treatment and management options on Australian guidelines, with consideration given to the potential fracture risk reduction and survival benefits. Skeletal age was estimated as the sum of chronological age and years of life lost due to a fracture or exposure to risk factors that elevate mortality risk. Conclusions: BONEcheck is an innovative tool that empowers doctors and patients to engage in well-informed discussions and make decisions based on the patient's risk profile. Public access to BONEcheck is available via https://bonecheck.org and in Apple Store (iOS) and Google Play (Android).

Prevention of Hip Fractures: Trade-off between Minor Benefits to Individuals and Large Benefits to the Community.

Goeffrey Rose postulated that a population-based measure bringing a small benefit to each individual can yield large benefits to the community. We aimed to test this axiom by quantifying the relationship between change in bone mineral density (BMD) and hip fracture incidence between two prospective cohorts separated by ~10 years. In this prospective population-based Dubbo Osteoporosis Epidemiology Study (DOES), the participants aged 60+ were recruited in two waves: the initial cohort (1311 women, 842 men) in 1989 to 1992 and the second cohort (974 women, 544 men) in 1999 to 2001. The incident hip fracture was radiologically ascertained. Femoral neck BMD was measured biannually. Multivariable-adjusted Cox's proportional hazards models were adjusted for the predefined covariates such as age, BMI, lifestyle factors, falls, and prior fracture. Compared with the initial cohort, the second cohort had a higher femoral neck BMD by ~0.04 g/cm2 in women and 0.03 g/cm2 in men. However, the prevalence of osteoporosis in the second cohort was halved (prevalence ratio 0.51, 95% CI 0.36 to 0.73 in women; 0.45, 0.24 to 0.84 in men), and its hip fracture incidence was significantly reduced (hazard ratio 0.54, 95% CI, 0.38 to 0.78 in women; 0.39, 0.19 to 0.80 in men). Sensitivity analyses indicated that the "effect" was unlikely due to unmeasured confounders. These findings suggest that a population-wide strategy aimed at enhancing BMD across the entire population could lead to a substantial decrease in the incidence of hip fractures. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Genetic Prediction of Lifetime Risk of Fracture.

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.

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.

Two-Thirds of All Fractures Are Not Attributable to Osteoporosis and Advancing Age: Implications for Fracture Prevention.

CONTEXT: Although bone mineral density (BMD) is strongly associated with fracture and postfracture mortality, the burden of fractures attributable to low BMD has not been investigated. OBJECTIVES: We sought to estimate the population attributable fraction of fractures and fracture-related mortality that can be attributed to low BMD. DESIGN AND SETTING: This study is a part of an ongoing population-based prospective cohort study, the Dubbo Osteoporosis Epidemiology study. In total, 3700 participants aged ≥50 years participated in the study. Low-trauma fracture was ascertained by X-ray reports, and mortality was ascertained from the Birth, Death and Marriage Registry. RESULTS: Overall, 21% of women and 11% of men had osteoporotic BMD. In univariable analysis, 21% and 16% of total fractures in women and men, respectively, were attributable to osteoporosis. Osteoporosis combined with advancing age (>70 years) accounted for 34% and 35% of fractures in women and men, respectively. However, these two factors accounted for ∼60% of hip fractures. About 99% and 66% of postfracture mortality in women and men, respectively, were attributable to advancing age, osteoporosis, and fracture; however, most of the attributable proportion was accounted for by advancing age. CONCLUSIONS: A substantial health care burden of fracture is on people aged <70 years or nonosteoporosis, suggesting that treatment of people with osteoporosis is unlikely to reduce a large number of fractures in the general population.

Low-trauma rib fracture in the elderly: Risk factors and mortality consequence.

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/cm2) 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.

Prediction of changes in bone mineral density in the elderly: contribution of "osteogenomic profile".

The contribution of genetic variants to longitudinal bone loss has not been well documented. We constructed an "osteogenomic profile" based on 62 BMD-associated genetic variants and showed that the profile was significantly associated with bone loss, independently from baseline BMD and age. The osteogenomic profile can help predict bone loss in an individual. INTRODUCTION: The rate of longitudinal bone loss (ΔBMD) is a risk factor for fracture. The variation in ΔBMD is partly determined by genetic factors. This study sought to define the association between an osteogenomic profile and ΔBMD. METHODS: The osteogenomic profile was created from 62 BMD-associated SNPs from genome-wide association studies (GWAS) that were genotyped in 1384 elderly men and women aged 60+ years. Weighted genetic risk scores (GRS) were constructed for each individual by summing the products of the number of risk alleles and the sex-specific regression coefficients [associated with BMD from GWAS]. ΔBMD, expressed as annual percent change-in-BMD, was determined by linear regression analysis for each individual who had had at least two femoral neck BMD measurements. RESULTS: The mean ΔBMD was - 0.65% (SD 1.64%) for women and - 0.57% (SD 1.40%) for men, and this difference was not statistically significant (P = 0.32). In women, each unit increase in GRS was associated with 0.21% (SE 0.10) higher ΔBMD at the femoral neck (P = 0.036), and this association was independent of baseline BMD and age. In logistic regression analysis, each unit increase of GRS was associated with 41% odds (95%CI: 1.07-1.87) of rapid bone loss (ΔBMD ≤ - 1.2%/year; mean of rapid loss group = - 2.2%/year). There was no statistically significant association between ΔBMD and GRS in men. CONCLUSIONS: We conclude that the osteogenomic profile constructed from BMD-associated genetic variants is modestly associated with long-term changes in femoral neck BMD in women, but not in men.

Sex-difference in bone architecture and bone fragility in Vietnamese.

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.

Prediction of hip fracture in post-menopausal women using artificial neural network approach.

Hip fracture is one of the most serious health problems among post-menopausal women with osteoporosis. It is very difficult to predict hip fracture, because it is affected by multiple risk factors. Existing statistical models for predicting hip fracture risk yield area under the receiver operating characteristic curve (AUC) ~0.7-0.85. In this study, we trained an artificial neural network (ANN) to predict hip fracture in one cohort, and validated its predictive performance in another cohort. The data for training and validation included age, bone mineral density (BMD), clinical factors, and lifestyle factors which had been obtained from a longitudinal study that involved 1167 women aged 60 years and above. The women had been followed up for up to 10 years, and during the period, the incidence of new hip fractures was ascertained. We applied feed-forward neural networks to learn from the data, and then used the learning for predicting hip fracture. Results of prediction showed that the accuracy of model I (which included only lumbar spine and femoral neck BMD) and model II (which included non-BMD factors) was 82% and 84%, respectively. When both BMD and non-BMD factors were combined (Model III), the accuracy increased to 87%. The AUC for model III was 0.94. These findings indicate that ANNs are able to predict hip fracture more accurately than any existing statistical models, and that ANNs can help stratify individuals for clinical management.

Patterns of antimicrobial resistance in intensive care unit patients: a study in Vietnam.

BACKGROUND: Antimicrobial resistance has emerged as a major concern in developing countries. The present study sought to define the pattern of antimicrobial resistance in ICU patients with ventilator-associated pneumonia. METHODS: Between November 2014 and September 2015, we enrolled 220 patients (average age ~ 71 yr) who were admitted to ICU in a major tertiary hospital in Ho Chi Minh City, Vietnam. Data concerning demographic characteristics and clinical history were collected from each patient. The Bauer-Kirby disk diffusion method was used to detect the antimicrobial susceptibility. RESULTS: Antimicrobial resistance was commonly found in ceftriaxone (88%), ceftazidime (80%), ciprofloxacin (77%), cefepime (75%), levofloxacin (72%). Overall, the rate of antimicrobial resistance to any drug was 93% (n = 153/164), with the majority (87%) being resistant to at least 2 drugs. The three commonly isolated microorganisms were Acinetobacter (n = 75), Klebsiella (n = 39), and Pseudomonas aeruginosa (n = 29). Acinetobacter baumannii were virtually resistant to ceftazidime, ceftriaxone, piperacilin, imipenem, meropenem, ertapenem, ciprofloxacin and levofloxacin. High rates (>70%) of ceftriaxone and ceftazidime-resistant Klebsiella were also observed. CONCLUSION: These data indicated that critically ill patients on ventilator in Vietnam were at disturbingly high risk of antimicrobial resistance. The data also imply that these Acinetobacter, Klebsiella, and Pseudomonas aeruginosa and multidrug resistance pose serious therapeutic problems in ICU patients. A concerted and systematic effort is required to rapidly identify high risk patients and to reduce the burden of antimicrobial resistance in developing countries.

Prediction of Bone Mineral Density and Fragility Fracture by Genetic Profiling.

Although the susceptibility to fracture is partly determined by genetic factors, the contribution of newly discovered genetic variants to fracture prediction is still unclear. This study sought to define the predictive value of a genetic profiling for fracture prediction. Sixty-two bone mineral density (BMD)-associated single-nucleotide polymorphisms (SNPs) were genotyped in 557 men and 902 women who had participated in the Dubbo Osteoporosis Epidemiology Study. The incidence of fragility fracture was ascertained from X-ray reports between 1990 and 2015. Femoral neck BMD was measured by dual-energy X-ray absorptiometry. A weighted polygenic risk score (genetic risk score [GRS]) was created as a function of the number of risk alleles and their BMD-associated regression coefficients for each SNP. The association between GRS and fracture risk was assessed by the Cox proportional hazards model. Individuals with greater GRS had lower femoral neck BMD (p < 0.01), but the variation in GRS accounted for less than 2% of total variance in BMD. Each unit increase in GRS was associated with a hazard ratio of 1.20 (95% CI, 1.04 to 1.38) for fracture, and this association was independent of age, prior fracture, fall, and in a subset of 33 SNPs, independent of femoral neck BMD. The significant association between GRS and fracture was observed for the vertebral and wrist fractures, but not for hip fracture. The area under the receiver-operating characteristic (ROC) curve (AUC) for the model with GRS and clinical risk factors was 0.71 (95% CI, 0.68 to 0.74). With GRS, the correct reclassification of fracture versus nonfracture ranged from 12% for hip fracture to 23% for wrist fracture. A genetic profiling of BMD- associated genetic variants could improve the accuracy of fracture prediction over and above that of clinical risk factors alone, and help stratify individuals by fracture status. © 2016 American Society for Bone and Mineral Research.

Association of Muscle Weakness With Post-Fracture Mortality in Older Men and Women: A 25-Year Prospective Study.

Osteoporotic fracture increases the risk of premature mortality. Muscle weakness is associated with both increased fracture risk and low bone mineral density (BMD). However, the role of muscle strength in post-fracture mortality is not well understood. This study examines the change of muscle strength measured at quadriceps (QS) before and after fracture and defines the relationship between muscle strength and post-fracture mortality. The study involved 889 women and 295 men (who were participating in the Dubbo Osteoporosis Study) who had at least one low-trauma fracture (ascertained from X-ray reports) after the age of 50 years. Median follow-up time was 11 years (range 1 to 24). To determine the change in muscle strength before and after a fracture, we selected a subset of 344 women and 99 men who had had at least two muscle strength measurements before the fracture event and a subset of 407 women and 105 men who had had at least two measurements after the fracture. During the follow-up period, 366 (41.2%) women and 150 (50.9%) men died. The annual rate of decrease in height-adjusted muscle strength before fracture was 0.27 kg/m (1.85%) in women and 0.40 kg/m (1.79%) in men. Strength loss after fracture was not significantly different from that before fracture. In women, after adjusting for baseline age and BMD, each SD (5 kg/m) lower height-adjusted pre- and post-fracture quadriceps strength was associated with a 27% (hazard ratio [HR] = 1.27; 95% confidence interval [CI] 1.07, 1.50) and 18% (HR = 1.18; 95% CI 1.01, 1.38) increase in post-fracture mortality risk, respectively. Similarly, in men, each SD (5 kg/m) lower height-adjusted pre- and post-fracture QS was associated with increased mortality before fracture (HR = 1.33; 95% CI 1.09, 1.63) and after fracture (HR = 1.43; 95% CI 1.16, 1.78). Muscle weakness accounted for 15% (95% CI 0.05, 0.24) of premature deaths after fracture in women and 23% (95% CI 0.11, 0.35) in men. These results indicate that in the older individuals, lower muscle strength is an independent risk factor for post-fracture mortality. © 2017 American Society for Bone and Mineral Research.