Establish and validate the reliability of predictive models in bone mineral density by deep learning as examination tool for women.

While FRAX with BMD could be more precise in estimating the fracture risk, DL-based models were validated to slightly reduce the number of under- and over-treated patients when no BMD measurements were available. The validated models could be used to screen for patients at a high risk of fracture and osteoporosis. PURPOSE: Fracture risk assessment tool (FRAX) is useful in classifying the fracture risk level, and precise prediction can be achieved by estimating both clinical risk factors and bone mineral density (BMD) using dual X-ray absorptiometry (DXA). However, DXA is not frequently feasible because of its cost and accessibility. This study aimed to establish the reliability of deep learning (DL)-based alternative tools for screening patients at a high risk of fracture and osteoporosis. METHODS: Participants were enrolled from the National Bone Health Screening Project of Taiwan in this cross-sectional study. First, DL-based models were built to predict the lowest T-score value in either the lumbar spine, total hip, or femoral neck and their respective BMD values. The Bland-Altman analysis was used to compare the agreement between the models and DXA. Second, the predictive model to classify patients with a high fracture risk was built according to the estimated BMD from the first step and the FRAX score without BMD. The performance of the model was compared with the classification based on FRAX with BMD. RESULTS: Approximately 10,827 women (mean age, 65.4 ± 9.4 years) were enrolled. In the prediction of the lumbar spine BMD, total hip BMD, femoral neck BMD, and lowest T-score, the root-mean-square error (RMSE) was 0.099, 0.089, 0.076, and 0.68, respectively. The Bland-Altman analysis revealed a nonsignificant difference between the predictive models and DXA. The FRAX score with femoral neck BMD for major osteoporotic fracture risk was 9.7% ± 6.7%, whereas the risk for hip fracture was 3.3% ± 4.6%. Comparison between the classification of FRAX with and without BMD revealed the accuracy rate, positive predictive value (PPV), and negative predictive value (NPV) of 78.8%, 64.6%, and 89.9%, respectively. The area under the receiver operating characteristic curve (AUROC), accuracy rate, PPV, and NPV of the classification model were 0.913 (95% confidence interval: 0.904-0.922), 83.5%, 71.2%, and 92.2%, respectively. CONCLUSION: While FRAX with BMD could be more precise in estimating the fracture risk, DL-based models were validated to slightly reduce the number of under- and over-treated patients when no BMD measurements were available. The validated models could be used to screen for patients at a high risk of fracture and osteoporosis.

Demographics and medical burden of osteogenesis imperfecta: a nationwide database analysis.

The epidemiological data on osteogenesis imperfecta (OI) in Asia is limited. This study, representing the first comprehensive epidemiological investigation on OI in Taiwan, reveals high medical resource utilization and underscores the importance of early diagnosis to enhance care quality. INTRODUCTION: This study examines osteogenesis imperfecta, a hereditary connective tissue disorder causing pediatric fractures and limb deformities, using a nationwide database from Taiwan to analyze clinical features and medical burden. METHODS: The study identified validated OI patients from the Catastrophic Illness Registry in the National Health Insurance Research Database from 2008 to 2019. Demographic data and medical resource utilization were analyzed. A multivariate Cox model assessed the influence of sex, validation age, and comorbidities. RESULTS: 319 OI patients (M/F = 153/166) were identified, with 58% validated before age 20. Prevalence and incidence were 0.8-1.3/100,000 and 0.02-0.09/100,000, respectively, with higher rates in the pediatric demographic. In the study period, 69.6% of the patients had admission history, primarily to pediatric and orthopedic wards. The median admission number was 3, with a median length of stay of 12 days and a median inpatient cost of approximately 3,163 USD during the period. Lower limb fractures were the main reason for hospitalization. 57% of OI patients received bisphosphonate treatment. The leading causes of mortality were OI-related deaths, neurovascular disease, and cardiovascular disease. The median age of validation in the non-survival group was significantly higher compared to the survival group (33 vs. 14 years), and patients validated during childhood required more inpatient fracture surgeries than those validated during adulthood. CONCLUSION: This study provides comprehensive real-world evidence on the clinical characteristics and high medical resource utilization of OI patients in a low prevalence region like Taiwan. Early diagnosis is crucial for improving care quality and enhancing health outcomes.

Drug adherence and treatment duration for denosumab and mortality risk among hip fracture patients.

This study aimed to assess the impact of drug adherence and treatment duration for denosumab on mortality risk after hip fracture surgery. Lower all-cause mortality risk was associated with drug intervals of 7 months or less and longer treatment duration. The study highlights the importance of proper denosumab administration. PURPOSE: Prescription of anti-osteoporotic medications (AOMs) after osteoporotic hip fracture may increase bone mineral density (BMD) and decrease mortality risk. However, few studies have been conducted on drug adherence and treatment duration for denosumab, a popular choice among AOMs. This study aimed to assess the impact of denosumab adherence and treatment duration on the mortality risk of hip fracture patients after surgery. METHODS: We conducted a cohort study using nationwide population data from National Health Insurance Research Database (NHIRD) in Taiwan. Patients newly diagnosed with osteoporosis and hip fracture between 2008 and 2019 who used denosumab after surgery were included. We assessed drug adherence, treatment duration, and other parameters associated with patient outcomes. RESULTS: A total of 21,316 patients diagnosed with osteoporotic hip fractures were included. Compared with a > 7-month drug interval for denosumab, an interval of ≤ 7 months led to lower all-cause mortality risk (hazard ratio (HR): 0.60, 95% confidence interval (CI): 0.57 ~ 0.64). Patients with denosumab treatment for over 1, 2, and 3 years had lower all-cause mortality risk (HR&CI: 0.68 (0.64 ~ 0.73), 0.48 (0.43 ~ 0.53), 0.29 (0.26 ~ 0.33)) than those with treatment duration < 1 year. Analysis after excluding short-term death yielded similar results. Analysis of causes of death also showed that good adherence and longer duration were associated with reduced mortality due to cancer and cardiovascular disease. CONCLUSION: Better drug adherence and longer duration of denosumab treatment are associated with lower all-cause mortality risk among hip fracture patients after surgery. Our study highlights the benefits of a proper time interval of denosumab administration. These findings provide important insight into management of osteoporotic hip fractures and may inform clinical practice and development of guidelines.

Association of bisphosphonates with diabetes risk and glycemic control: a meta-analysis.

Previous evidence suggests that bisphosphonates may improve glycemic control. The present meta-analysis, comprising seven studies with 1,233,844 participants, demonstrated that bisphosphonate use was significantly associated with a lower risk of diabetes. However, in the randomized controlled trial subgroup, a non-significant association was found. Further studies are needed to determine causality. PURPOSE: This study aimed to evaluate the impact of bisphosphonates on glycemic control and the risk of incident diabetes. METHODS: MEDLINE, Embase, and Cochrane Library were searched from inception to February 15, 2022. Experimental or observational studies that compared fasting blood glucose (FBG) and glycated hemoglobin (HbA1c) levels and the diabetes risk with and without bisphosphonates were included. Studies without relevant outcomes, only providing crude estimates, or the absence of a control group were excluded. Two reviewers independently screened the articles, extracted data, and appraised studies. The pooled relative risk (RR) and weighted mean difference (WMD) were calculated using random effects models. RESULTS: Seven studies (n = 1,233,844) on diabetes risk were included, including two post hoc analyses of randomized controlled trials (RCTs) and five observational studies. Compared with controls, bisphosphonates (BPs) were associated with a significant decrease in the risk of diabetes (RR = 0.77; 95% CI, 0.65 to 0.90; P = 0.002). However, in the subgroup of post hoc analyses of RCTs, the association was non-significant (RR = 0.93; 95% CI, 0.74 to 1.18; P = 0.576). Moreover, three studies (n = 4906) on FBG and one (n = 60) on HbA1c were included. We observed non-significant association between BPs and changes in FBG (WMD = - 0.61 mg/dL; 95% CI, - 2.72 to 1.49; P = 0.567) and HbA1c (WMD = - 0.11%; 95% CI, - 0.23 to 0.01; P = 0.083). CONCLUSION: Patients taking BPs may have a lower risk of incident diabetes than those without BPs. However, due to the high between-study heterogeneity and inconsistent findings between post hoc analyses of RCTs and observational studies, further rigorous RCTs are required to determine whether the findings are causal.

Association between bisphosphonate use and stroke risk: a meta-analysis.

Previous studies have suggested that bisphosphonates may reduce stroke risk. This meta-analysis, which included 21 studies with 741,274 participants, revealed that bisphosphonates might be associated with lower stroke risk. However, evidence derived from randomized controlled trials identified no statistically significant association. Future high-quality studies are still required to determine causality. PURPOSE: Whether bisphosphonates may reduce the risk of stroke remains inconclusive. We conducted a systematic review and meta-analysis to evaluate the association between bisphosphonate use and the risk of stroke based on up-to-date evidence. METHODS: We searched for studies evaluating the effects of bisphosphonate on the risk of stroke from inception until January 3, 2022, on PubMed, Embase, Scopus, and Cochrane libraries and updated our search until August 22, 2022, using PubMed to identify any new potential published studies. Two or more reviewers independently screened articles, extracted data, and assessed the study quality. We retrieved the data to synthesize the pooled relative risk (RR) of stroke associated with bisphosphonate use compared with controls; random-effects models were used for meta-analysis. RESULTS: A total of 21 studies (7 randomized controlled trials [RCTs] and 14 observational studies) involving 741,274 participants were included in our meta-analysis. Overall, bisphosphonate use was associated with a lower risk of stroke, but the result was only borderline significant (pooled RR = 0.87, 95% confidence interval [CI]: 0.76-0.99, p = 0.048), and high between-study heterogeneity was found (I2 = 83.7%). Subgroup analyses showed that the evidence derived from RCTs suggested no significant association between bisphosphonate use and stroke risk (pooled RR = 0.93, 95% CI: 0.76-1.13, p = 0.462; I2 = 13.4%). CONCLUSION: Our results suggest that bisphosphonate use is associated with a lower risk of stroke. However, the current evidence does not lead to a definite conclusion due to the borderline statistical significance and high between-study heterogeneity. Future studies, especially RCTs, are necessary to assess causality.

Osteoporosis care after hip fracture: Observation from national health insurance database and fracture liaison services.

BACKGROUND: The objective of this research was to report the trend of osteoporosis care after hip fractures from usual care (UC) and to compare the quality of care with those who received fracture liaison services (FLSs). METHODS: Data on osteoporosis care for patients with hip fracture were acquired from the National Health Insurance claims (UC group), and surveys from FLS programs (FLS group). A total of 183,300 patients receiving UC and 3010 patients receiving FLS were studied. For the two groups, common osteoporosis care indicators, such as bone mineral density (BMD) testing rate, antiosteoporosis medication commencement rate, and adherence rate were described. RESULTS: There were 2488 participants (82.7%) in the FLS group who completed Dual-energy X-ray absorptiometry (DXA) in 8 weeks, 155 (5.1%) who finished it between 8 weeks and 1 year. Even in 2018, when the DXA completion rate was at its highest, the completion rate in the UC group was only 23.5%. In terms of medication commencement, 2372 FLS patients (78.8%) received treatment within 3 months. Only 24.9% of the UC patients received antiosteoporosis medication within 3 months. Furthermore, antiosteoporosis medication adherence rate was 92.2% after 1 year and 83.9% after 2 years in the FLS group, but these were only 66.5% and 42.7%, respectively, in the UC group. CONCLUSION: Patients who received FLS had more timely BMD exams, antiosteoporosis medication treatment, and higher adherence to antiosteoporosis therapy than those who received UC. The discrepancy in rates of continuing treatment became more significant over time between both groups.

Cost and effectiveness analyses of the anti-osteoporosis medication in patients with hip fracture in Taiwan: A population-based national claims database analysis.

BACKGROUND: Real-world cost and effectiveness analyses of the anti-osteoporosis medications (AOM) using a nationwide database in Asia were limited. The aim of this study was to evaluate the cost and effectiveness of AOMs therapy under the reimbursement of National Health Insurance in Taiwan. METHODS: Using Taiwan's National Health Insurance Research Database, patients who had hospitalization due to incident hip fractures with related operation between 2008 and 2017 were identified as our study population. Patients who initiated AOMs within 1 year post incident hip fracture were matched with those did not according to the propensity score. The direct medical cost and subsequent fracture within three years were estimated. Statistically significant differences of risk for subsequent fracture between the AOM and non-AOM groups were estimated using the COX proportional hazards model. All costs were presented as New Taiwan Dollars (NTD). RESULTS: There were 27,357 new hip fracture patients who initiated AOMs, and 76% of them were women with a mean age of 77.7 years. Among patients ages ≥70 who encountered hip fractures, those who initiated AOMs experienced fewer non-vertebral fractures (HR = 1.07 (1.02-1.13), p = 0.0114 for those ages 70-79 years old; HR = 1.11 (1.06-1.17), p < 0.0001 for those ages ≥80 years) and mortality (HR = 1.18 (1.14-1.22), p < 0.0001 for those ages 70-79; HR = 1.20 (1.16-1.23), p < 0.0001) within 3 years post incident fracture; meanwhile, consuming fewer medical resources in the national insurance healthcare system. (Increment cost = -16011.2 NTD, p = 0.0248 for those ages 70-79; Increment cost = -17257.9 NTD, p = 0.0032 for those ages ≥80 years) CONCLUSION: Overall, under Taiwan's national health insurance, the use of AOMs is cost-saving, especially in the population aged ≥70 years. The finding of this research was valuable for policymakers in considering healthcare policy promotion and resource allocation in the future.

Epidemiology and clinical impact of osteoporosis in Taiwan: A 12-year trend of a nationwide population-based study.

BACKGROUND: Osteoporosis increases the fracture and mortality risk of patients and has a higher disease burden than some cancers. Therefore, global concerns regarding the prevention and treatment of osteoporosis have been raised. However, fast-aging Taiwan lacks national epidemiological data on osteoporosis in recent years. We aimed to establish and update epidemiological data on osteoporosis by analyzing national data from 2008 to 2019. METHODS: We estimated the prevalence and incidence of osteoporosis in patients aged ≥50 years based on claims data from Taiwan's National Health Insurance database from 2008 to 2019. We also analyzed the key parameters of fracture care (anti-osteoporosis medication use, bone mineral density examination rate, and length of hospital stay) to understand the secular trend of management and related clinical outcomes (imminent refracture rate and mortality). RESULTS: The number of prevalent osteoporosis increased from 2008 to 2015 and remained constant until 2019; however, the age-standardized prevalence and incidence rates declined from 2008 to 2019 (3.77%-2.91% and 2.08%-1.02%, respectively). The overall incidence rates of hip and spine fractures decreased significantly by 34% and 27%, respectively. For patients with hip and spine fractures, the immanent refracture rates were 8.5% and 12.9% and the 1-year mortality rate remained stable at approximately 15% and 6%, respectively. CONCLUSION: The age-standardized prevalence and incidence rates decreased remarkably from 2008 to 2019, while the number of prevalent osteoporosis remained steady. Patients with hip fractures encountered a high 1-year mortality rate, while the risk of imminent refracture was notable for patients with spine fractures.

The real-world adherence of the first-line anti-osteoporosis medications in Taiwan: Visualize the gap between reality and expectations.

BACKGROUND: Adherence to anti-osteoporosis medications (AOMs) is crucial. National Health Insurance (NHI) in Taiwan has its own rules of reimbursement rule for AOMs. The midterm adherence remained inconclusive. Here we investigated the adherence according to the initially used AOMs, for three consecutive years. METHODS: The nationwide cohort study from 2008 to 2018, based on Taiwan's National Health Insurance Research Database, included 336,229 patients. Their adherence, indicated by medication possession ratio (MPR), to the initial AOMs was investigated yearly for three consecutive years. The overall MPRs (OMPR), including the switched AOMs, were also calculated in the first year. The Sankey diagram further visualized the patient flows toward different adherence according to the initial AOMs. RESULTS: The OMPR in the first year improved if the patients used AOMs with longer dosing intervals. 100%, 68.9%, 40.7%, and 34.0% of the patients started the treatment with zoledronate, denosumab, alendronate, and raloxifene, respectively, had OMPR ≥75% in the first year. In the 3rd year, only 20.89%, 24.13%, and 12.83% of the patients continuously treated with zoledronate, denosumab, and alendronate, respectively, had MPR ≥75%. From the Sankey diagram, we also observed that patients who had poor adherence at one year were inclined to have poor adherence or discontinue antiosteoporosis treatment in the next year. CONCLUSION: The initial AOMs and the observed adherence may provide clues for optimizing patient treatment. The real-world adherence in Taiwan was far from satisfactory in our study.

Eleven years secular trend of the initiation of anti-osteoporosis medications and subsequent fractures in Taiwan: From 2008 to 2018.

BACKGROUND: Osteoporosis is a common metabolic bone disease that benefits from many newly developed anti-osteoporosis medications (AOMs). Reimbursement policies need to allocate medical budgets properly based on evidence-based data. This study aimed to investigate the 11-year secular trend, focusing on older age and males in this adjustment wave of the National Health Insurance reimbursement. METHODS: We adopted a nationwide cohort from Taiwan's National Health Insurance Research Database (NHIRD). Patients undergoing newly initiated AOMs from 2008 to 2018 were included. The AOMs in this study included denosumab, zoledronate, ibandronate, alendronate, raloxifene, and risedronate. Patients <50 years, pathological fractures, missing data, and two AOMs prescribed were excluded. The real-world trends related to subsequent fragility fracture and death within 1 and 3 years were used to evaluate the potential effects due to revision of reimbursement policies. RESULTS: Of 393,092 patients, among them, 336,229 patients met the criteria, whose mean age ranged from 73.3 to 74.4 years, and nearly 80% were female. Further analysis showed a steady increase of AOMs from 5567 (17.1%) and 8802 (27.0%) in 2008-6697 (18.3%) and 10,793 (29.5%) in 2018 for males and 80+ years respectively. The subsequent fragility fracture within one and three years post AOMs initiation was 5.81% and 11.80% in 2018. CONCLUSION: This study showed an immediate drop in AOMs prescription after the implementation of a new stricter reimbursement policy. It took 5 years to return the annual prescription number.

Constraining in reimbursement criteria and the adherence to anti-osteoporosis medications (AOMs) in Taiwan: Urbanization makes the difference.

BACKGROUND: The Bureau of National Health Insurance in Taiwan implemented a new reimbursement scheme incorporating bone mineral density (BMD) criteria on Jan. 1, 2011. This study aimed to investigate a real-life 11-year secular trend of adherence in new AOMs users and evaluated the change of adherence to AOMs therapy in different urbanization areas after reimbursement criteria were restrained. METHODS: We used Taiwan's National Health Insurance Research Database to identify new AOMs users as our study population. The AOMs in this study included denosumab, zoledronate, ibandronate, alendronate, raloxifene, and risedronate. The first prescription date of AOMs was defined as the cohort entry date. The adherence rates within one year after initiation were assessed. RESULTS: High adherence (≥75%) in the first year increased markedly after the new reimbursement scheme in 2011, changing from 31.8% in 2008, and 41.7% in 2011 to 54.2% in 2018. On the other hand, low adherence (<25%) decreased from 38.8% in 2008 to 14.6% in 2018. In addition, the switchers increased from 5.9% in 2008 to 9.3% in 2018, indicating a more flexible choice of AOMs. The proportion of high adherence to AOMs was highest in high-urbanization areas, and the proportion increased about two times from 30% in 2008 to 60% in 2018. CONCLUSION: The implementation of new reimbursement criteria in 2011 was associated with increased adherence to AOMs and the increase was most apparent in high-urbanization areas.

Refracture risk and all-cause mortality after vertebral fragility fractures: Anti-osteoporotic medications matter.

BACKGROUND: Osteoporotic vertebral fractures may predict the future occurrence of fractures and increase mortality. Treating underlying osteoporosis may prevent second fractures. However, whether anti-osteoporotic treatment can reduce the mortality rate is not clear. The aim of this population study was to identify the degree of decreased mortality following the use of anti-osteoporotic medication after vertebral fractures. METHODS: We identified patients who had newly diagnosed osteoporosis and vertebral fractures from 2009 to 2019 using the Taiwan National Health Insurance Research Database (NHIRD). We used national death registration data to determine the overall mortality rate. RESULTS: There were 59,926 patients with osteoporotic vertebral fractures included in this study. After excluding patients with short-term mortality, patients who had previously received anti-osteoporotic medications had a lower refracture rate as well as a lower mortality risk (hazard ratio (HR): 0.84, 95% confidence interval (CI): 0.81-0.88). Patients receiving treatment for more than 3 years had a much lower mortality risk (HR: 0.53, 95% CI: 0.50-0.57). Patients who used oral bisphosphonates (alendronate and risedronate, HR: 0.95, 95% CI: 0.90-1.00), intravenous zoledronic acid (HR: 0.83, 95% CI: 0.74-0.93), and subcutaneous denosumab injections (HR: 0.71, 95% CI: 0.65-0.77) had lower mortality rates than patients without further treatment after vertebral fractures. CONCLUSION: In addition to fracture prevention, anti-osteoporotic treatments for patients with vertebral fractures were associated with a reduction in mortality. A longer duration of treatment and the use of long-acting drugs was also associated with lower mortality.

Clinical practice guidelines for the prevention and treatment of osteoporosis in Taiwan: 2022 update.

Osteoporosis greatly increases the risk of fractures. Osteoporotic fractures negatively impact quality of life, increase the burden of care, and increase mortality. Taiwan is an area with a high prevalence of osteoporosis. This updated summary of guidelines has been developed by experts of the Taiwan Osteoporosis Association with the intention of reducing the risks of osteoporotic fractures and improving the quality of care for patients with osteoporosis. The updated guidelines compile the latest evidence to provide clinicians and other healthcare professionals with practical recommendations for the prevention, diagnosis, and management of osteoporosis under clinical settings in Taiwan.

Diagnostic accuracy of algorithms to define incident and second hip fractures: A Taiwan validation study.

BACKGROUND: Previous epidemiological researchers have used various algorithms to identify a second hip fracture; however, there has been no validation of these algorithms to date. This study aimed to verify existing algorithms for identifying second hip fracture under the International Classification of Diseases diagnostic coding systems. Furthermore, we examined the validity of two newly proposed algorithms that integrated the concept of periprosthetic fractures and laterality of the ICD-10 coding system. METHODS: Claims data of patients hospitalized for hip fracture from National Taiwan University Hospitals between 2007 and 2020 were retrieved. Hip fracture was confirmed by 2 orthopaedic surgeons with medical records and imaging data as gold standards. The validity of 9 existing and 2 newly proposed algorithms for identifying second hip fracture was evaluated. RESULTS: The positive predictive value (PPV) range between 84% and 90% in existing algorithms for identifying second hip fractures. Noteworthy, the longer time interval for discrimination resulted in slightly increased PPV (from 87% to 90%), while decreased sensitivity noticeably (from 87% to 72%). When considering the information about periprosthetic fracture, the PPV increased to 91% without diminished sensitivity. The PPV of the newly proposed ICD-10-specific algorithm was 100%. CONCLUSION: Algorithms integrated clinical insights of periprosthetic fractures and laterality concept of ICD-10 coding system provided satisfactory validity and help precisely define second hip fracture in future database research.

Asia-pacific consensus on osteoporotic fracture prevention in postmenopausal women with low bone mass or osteoporosis but no fragility fractures.

Postmenopausal women are at significant risk for osteoporotic fractures due to their rapid bone loss. Half of all postmenopausal women will get an osteoporosis-related fracture over their lifetime, with 25% developing a spine deformity and 15% developing a hip fracture. By 2050, more than half of all osteoporotic fractures will occur in Asia, with postmenopausal women being the most susceptible. Early management can halt or even reverse the progression of osteoporosis. Consequently, on October 31, 2020, the Taiwanese Osteoporosis Association hosted the Asia-Pacific (AP) Postmenopausal Osteoporotic Fracture Prevention (POFP) consensus meeting, which was supported by the Asian Federation of Osteoporosis Societies (AFOS) and the Asia Pacific Osteoporosis Foundation (APOF). International and domestic experts developed ten applicable statements for the prevention of osteoporotic fractures in postmenopausal women with low bone mass or osteoporosis but no fragility fractures in the AP region. The experts advocated, for example, that postmenopausal women with a high fracture risk be reimbursed for pharmaceutical therapy to prevent osteoporotic fractures. More clinical experience and data are required to modify intervention tactics.

Discovering Hair Biomarkers of Alzheimer's Disease Using High Resolution Mass Spectrometry-Based Untargeted Metabolomics.

Hair may be a potential biospecimen to discover biomarkers for Alzheimer's disease (AD) since it reflects the integral metabolic profiles of body burden over several months. Here, we described the AD biomarker discovery in the hair using a high-resolution mass spectrometry (HRMS)-based untargeted metabolomics approach. A total of 24 patients with AD and 24 age- and sex-matched cognitively healthy controls were recruited. The hair samples were collected 0.1-cm away from the scalp and further cut into 3-cm segments. Hair metabolites were extracted by ultrasonication with methanol/phosphate-buffered saline 50/50 (v/v) for 4 h. A total of 25 discriminatory chemicals in hair between the patients with AD and controls were discovered and identified. The AUC value achieved 0.85 (95% CI: 0.72~0.97) in patients with very mild AD compared to healthy controls using a composite panel of the 9 biomarker candidates, indicating high potential for the initiation or promotion phase of AD dementia in the early stage. A metabolic panel combined with the nine metabolites may be used as biomarkers for the early detection of AD. The hair metabolome can be used to reveal metabolic perturbations for biomarker discovery. Investigating perturbations of the metabolites will offer insight into the pathogenesis of AD.

2022 Taiwan lipid guidelines for primary prevention.

Elevated circulating low-density lipoprotein cholesterol (LDL-C) is a major risk factor of atherosclerotic cardiovascular disease (ASCVD). Early control of LDL-C to prevent ASCVD later in life is important. The Taiwan Society of Lipids and Atherosclerosis in association with the other seven societies developed this new lipid guideline focusing on subjects without clinically significant ASCVD. In this guideline for primary prevention, the recommended LDL-C target is based on risk stratification. A healthy lifestyle with recommendations for foods, dietary supplements and alcohol drinking are described. The pharmacological therapies for LDL-C reduction are recommended. The aim of this guideline is to decrease the risk of ASCVD through adequate control of dyslipidemia in Taiwan.

Quantification of the Endogenous Adduction Level on Hemoglobin and Correlation with Albumin Adduction via Proteomics: Multiple Exposure Markers of Catechol Estrogen.

Catechol estrogens (CEs) are genotoxic metabolites whose detection is challenging due to their low concentrations and high variability in the blood. By intact protein and free CE measurement of the spiked hemolysate, endogenous CEs were revealed to mainly (>99%) exist as hemoglobin (Hb) adducts in red blood cells. In order to detect endogenous CE-Hb adducts, we developed a two-step method that involved protein precipitation and solid phase extraction to purify Hb from red blood cells, and the method was coupled with proteomics using liquid chromatography-tandem mass spectrometry. Using bottom-up proteomics and standard additions, we identified C93 and C112 of Hb-ß as the main adduction sites of Hb, and this accounted for CE-induced oxidization of adducted peptides by sample preparation. The non-adducted, adducted, and oxidized tryptic peptides that covered the same Hb-ß sequences were targeted by parallel reaction monitoring to determine the adduction level in red blood cells. A quantification limit (S/N < 8) below the endogenous CE-Hb adduction level with relative standard errors that ranged from 5 to 22% was achieved and applied to clinical samples. The human serum albumin (HSA) adduction levels from the same patient were also determined using a previously developed method (Anal. Chem.2019,91, 15922-15931). A positive correlation (R2 = 0.673) between the CE-HSA and CE-Hb adduction level was obtained from all clinical samples, and both levels were significantly (p < 0.005) higher for patients with breast cancer compared to healthy controls. However, double indexes derived from the red blood cell and the serum, respectively, provide higher precision and confidence in predicting cancer risk than the single index. This study reported an efficient sample preparation for proteomics-based Hb adducts and revealed the potential of using multiple blood proteins for developing more reliable and specific markers based on protein adductomics.

IL-20 is involved in obesity by modulation of adipogenesis and macrophage dysregulation.

IL-20 is a proinflammatory cytokine of the IL-10 family and involved in several diseases. However, the regulatory role of IL-20 in obesity is not well understood. We explored the function of IL-20 in the pathogenesis of obesity-induced insulin resistance by ELISA, Western blotting and flow cytometry. The therapeutic potential of IL-20 monoclonal antibody 7E for ameliorating diet-induced obesity was analysed in murine models. Higher serum IL-20 levels were detected in obese patients. It was upregulated in leptin-deficient (ob/ob), leptin-resistant (db/db) and high-fat diet (HFD)-induced murine obesity models. In vitro, IL-20 regulated the adipocyte differentiation and the polarization of bone marrow-derived macrophages into proinflammatory M1 type. It also caused inflammation and macrophage retention in adipose tissues by upregulating TNF-α, monocyte chemotactic protein 1 (MCP-1), netrin 1 and unc5b (netrin receptor) expression in macrophages and netrin 1, leptin and MCP-1 in adipocytes. IL-20 promoted insulin resistance by inhibiting glucose uptake in mature adipocytes through the SOCS-3 pathway. In HFD-induced obesity in mice, 7E treatment reduced body weight and improved glucose tolerance and insulin sensitivity; it also reduced local inflammation and the number of M1-like macrophages in adipose tissues. We have identified a critical role of IL-20 in obesity-induced inflammation and insulin resistance, and we conclude that IL-20 may be a novel target for treating obesity and insulin resistance in patients with metabolic disorders.

Consensus Statement on the Use of Bone Turnover Markers for Short-Term Monitoring of Osteoporosis Treatment in the Asia-Pacific Region.

Osteoporosis is a major health issue. By 2050, a greater than 2-fold increase in patients number with hip fractures will occur in Asia representing 50% of all hip fractures worldwide. For the Asia-Pacific (AP) region, more efforts on controlling osteoporosis and the subsequent fractures are crucial. Bone mineral density (BMD) by dual energy X-ray absorptiometry (DXA) is commonly used to diagnose osteoporosis and monitor osteoporosis treatment. However, the inconvenience, cost, limited availability of DXA and the delay in detection of BMD changes after treatment initiation support an important role for bone turnover markers (BTMs), as short-term tools to monitor therapy. With regards to low adherence rates of medical treatment of osteoporosis, the experts reached consensus on the use of BTMs for both raising awareness and short-term monitoring of osteoporosis treatment in the AP region. The experts endorse the use of BTMs, especially serum C-terminal telopeptide of type 1 collagen (CTX) and serum procollagen type 1 N propeptide (P1NP), as short-term monitoring tools to help clinicians assess the responses to osteoporosis therapies and appropriately adjust treatment regimens earlier than BMD. Either the absolute values or the degree of change from baseline in BTMs can be used to monitor the potential efficacy of osteoporosis therapies. The use of BTMs can be incorporated in osteoporosis care programs, such as fracture liaison service (FLS), to improve patient adherence and treatment outcomes. Encouraging sufficient reimbursement from health care systems may facilitate widespread use of BTMs in clinical practice in the AP region.