The risk of major adverse cardiovascular events in patients with systemic sclerosis: a nationwide, population-based cohort study.

OBJECTIVE: To assess the incidence and risk factors of major adverse cardiovascular events (MACE) in patients with systemic sclerosis (SSc). METHODS: We conducted a nationwide, population-based, cohort study using Taiwan's National Health Insurance Research Database. We performed propensity score matching (PSM) using a 1:2 ratio, resulting in inclusion of 1,379 patients with SSc and 2,758 non-SSc individuals in the analysis. We assessed the association between SSc and MACE using the multivariable Cox proportional hazard regression model with adjustment of time-dependent covariates and investigated risk factors of MACE in patients with SSc, shown as adjusted hazard ratios (aHRs) with 95% confidence intervals (CI). RESULTS: SSc was not significantly associated with the risk of MACE (aHR 1.04; 95% CI 0.77-1.42). Nevertheless, SSc was associated with increased risk of myocardial infarction (IRR 1.76; 95% CI 1.08-2.86) and peripheral arterial occlusion disease (IRR 3.67; 95% CI 2.84-4.74) but not with ischemic stroke (IRR 0.89; 95% CI 0.61-1.29). Factors independently associated with MACE in SSc patients included age (aHR 1.02), male gender (aHR 2.01), living in a suburban area (aHR 2.09), living in a rural area (aHR 3.00), valvular heart disease (aHR 4.26), rheumatoid arthritis (RA) (aHR 2.14), use of clopidogrel (aHR 26.65), and use of aspirin (aHR 5.31). CONCLUSIONS: The risk of MACE was not significantly increased in Taiwanese patients with SSc, and our investigation effectively identified the factors independently associated with MACE in SSc patients. Additionally, patients with SSc exhibited higher risks of MI and PAOD but not ischemic stroke.

High-fat diet induces depression-like phenotype via astrocyte-mediated hyperactivation of ventral hippocampal glutamatergic afferents to the nucleus accumbens.

Comorbidity exists between metabolic disorders and depressive syndrome with unclear mechanisms. To characterize the causal relationship, we adopted a 12-week high-fat diet (HFD) to induce metabolic disorder and depressive phenotypes in mice. Initially, we identified an enhanced glutamatergic input in the nucleus accumbens of HFD mice. Retrograde tracing and chemogenetic inhibition showed that the hyperactive ventral hippocampal glutamatergic afferents to the nucleus accumbens determined the exhibition of depression-like behavior in HFD mice. Using lentiviral knockdown and overexpression approaches, we proved that HFD-induced downregulation of glial glutamate transporters, GLAST and GLT-1, contributed to the observed circuit maladaptations and subsequent depression-like behaviors. Finally, we identified a potential therapeutic agent, riluzole, which could mitigate the HFD-induced behavioral deficits by normalizing the expressions of GLAST and GLT-1 and ventral hippocampal glutamatergic afferents to the nucleus accumbens. Overall, astrocyte-mediated disturbance in glutamatergic transmission underlies the metabolic disorder-related depressive syndrome and represents a therapeutic target for this subtype of depressive mood disorders.

RNA editing of 5-HT2C R impairs insulin secretion of pancreatic beta cells via altered store-operated calcium entry.

Recent studies emphasize the importance of 5-HT2C receptor (5-HT2C R) signaling in the regulation of energy homeostasis. The 5-HT2C R is the only G-protein-coupled receptor known to undergo post-transcriptional adenosine to inosine (A-to-I) editing by adenosine deaminase acting on RNA (ADAR). 5-HT2C R has emerged as an important role in the modulation of pancreatic ß cell functions. This study investigated mechanisms behind the effects of palmitic acid (PA) on insulin secretion in different overexpressed 5-HT2C R edited isoforms in pancreatic MIN6 ß cells. Results showed that the expressions of 5HT2C R and ADAR2 were upregulated in the pancreatic islets of mice fed with high-fat diet (HFD) compared to control mice. PA treatment significantly induced the expressions of 5-HT2C R and ADAR2 in pancreatic MIN6 ß cells. PA treatment significantly induced the editing of 5-HT2C R in pancreatic MIN6 ß cells. There was no significant difference in cell viability between naïve cells and three overexpressed 5-HT2C R edited isoforms in pancreatic MIN6 ß cells. Overexpressed 5-HT2C R edited isoforms showed reduced glucose-stimulated insulin secretion (GSIS) compared with green fluorescent protein (GFP) expressed cells. Moreover, 5-HT2C R edited isoforms displayed reduced endoplasmic reticulum (ER) calcium release and store-operated calcium entry (SOCE) activation, probably through inhibition of stromal interaction molecule 1 trafficking under PA treatment. Altogether, our results show that PA-mediated editing of 5-HT2C R modulates GSIS through alteration of ER calcium release and SOCE activation in pancreatic MIN6 ß cells.

Phosphatidylinositol-4-phosphate 5-kinase type 1α attenuates Aß production by promoting non-amyloidogenic processing of amyloid precursor protein.

Alzheimer's disease (AD) is characterized by a chronic decline in cognitive function and is pathologically typified by cerebral deposition of amyloid-ß peptide (Aß). The production of Aß is mediated by sequential proteolysis of amyloid precursor protein (APP) by ß- and γ-secretases, and has been implicated as the essential determinant of AD pathology. Previous studies have demonstrated that the level of phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2] in the membrane may potentially modulate Aß production. Given that PI(4,5)P2 is produced by type 1 phosphatidylinositol-4-phosphate 5-kinases (PIP5Ks), we sought to determine whether the level of PIP5K type Iα (PIP5K1A) can affect production of Aß by modulating the lipid composition of the membrane. Using a HEK-derived cell line that constitutively expresses yellow fluorescent protein-tagged APP (APP-YFP), we demonstrated that overexpression of PIP5K1A results in significant enhancement of non-amyloidogenic APP processing and a concomitant suppression of the amyloidogenic pathway, leading to a marked decrease in secreted Aß. Consistently, cells overexpressing PIP5K1A exhibited a significant redistribution of APP-YFP from endosomal compartments to the cell surface. Our findings suggest that PIP5K1A may play a critical role in governing Aß production by modulating membrane distribution of APP, and as such, the pathway may be a valuable therapeutic target for AD.

A Fluorogenic Molecule for Probing Islet Amyloid Using Flavonoid as a Scaffold Design.

Aggregation of polypeptides and proteins is commonly associated with human and other vertebrate diseases. For example, amyloid plaques consisting of amyloid-ß proteins are frequently identified in Alzheimer's disease and islet amyloid formed by islet amyloid polypeptide (IAPP, amylin) can be found in most patients with type 2 diabetes (T2D). Although many fluorescent dyes have been developed to stain amyloid fibrils, very few examples have been designed for IAPP. In this study, a series of environmentally sensitive fluorescent probes using flavonoid as a scaffold design are rationally designed and synthesized. One of these probes, namely 3-HF-ene-4'-OMe, can bind to IAPP fibrils but not nonfibrillar IAPP by exhibiting a much stronger fluorescent enhancement at 535 nm. In addition, this probe shows better detection sensitivity to IAPP fibrils compared with that of conventionally used thioflavin-T. We demonstrate that 3-HF-ene-4'-OMe can be used to monitor the kinetics of IAPP fibril formation in vitro even in the presence an amyloid inhibitor. To test the specificity of the probe, we attempt to incubate this probe with amyloid fibrils formed from other amyloidogenic proteins. Interestingly, this probe shows different responses when mixed with these fibrils, suggesting the mode of binding of this probe on these fibrils could be different. Moreover, we show that this probe is not toxic to pancreatic mouse ß-cells. Further structural optimization based on the structure of 3-HF-ene-4'-OMe may yield a specific probe for imaging islet amyloid in the pancreas. That would improve our understanding of the relationship between islet amyloid and T2D.

ErbB2 regulates autophagic flux to modulate the proteostasis of APP-CTFs in Alzheimer's disease.

Proteolytic processing of amyloid precursor protein (APP) C-terminal fragments (CTFs) by γ-secretase underlies the pathogenesis of Alzheimer's disease (AD). An RNA interference screen using APP-CTF [99-residue CTF (C99)]- and Notch-specific γ-secretase interaction assays identified a unique ErbB2-centered signaling network that was predicted to preferentially govern the proteostasis of APP-C99. Consistently, significantly elevated levels of ErbB2 were confirmed in the hippocampus of human AD brains. We then found that ErbB2 effectively suppressed autophagic flux by physically dissociating Beclin-1 from the Vps34-Vps15 complex independent of its kinase activity. Down-regulation of ErbB2 by CL-387,785 decreased the levels of C99 and secreted amyloid-ß in cellular, zebrafish, and mouse models of AD, through the activation of autophagy. Oral administration of an ErbB2-targeted CL-387,785 for 3 wk significantly improves the cognitive functions of APP/presenilin-1 (PS1) transgenic mice. This work unveils a noncanonical function of ErbB2 in modulating autophagy and establishes ErbB2 as a therapeutic target for AD.

Protein Glycation by Glyoxal Promotes Amyloid Formation by Islet Amyloid Polypeptide.

Protein glycation, also known as nonenzymatic glycosylation, is a spontaneous post-translational modification that would change the structure and stability of proteins or hormone peptides. Recent studies have indicated that glycation plays a role in type 2 diabetes (T2D) and neurodegenerative diseases. Over the last two decades, many types of advanced glycation end products (AGEs), formed through the reactions of an amino group of proteins with reducing sugars, have been identified and detected in vivo. However, the effect of glycation on protein aggregation has not been fully investigated. In this study, we aim to elucidate the impact of protein glycation on islet amyloid polypeptide (IAPP, also known as amylin) aggregation, which was strongly associated with T2D. We chemically synthesized glycated IAPP (AGE-IAPP) to mimic the consequence of this hormone peptide in a hyperglycemia (high blood sugar) environment. Our data revealed that AGE-IAPP formed amyloid faster than normal IAPP, and higher-molecular-weight AGE-IAPP oligomers were also observed in the early stage of aggregation. Circular dichroism spectra also indicated that AGE-IAPP exhibited faster conformational changes from random coil to its ß-sheet fibrillar states. Moreover, AGE-IAPP can induce normal IAPP to expedite its aggregation process, and its fibrils can also act as templates to promote IAPP aggregation. AGE-IAPP, like normal IAPP, is capable of interacting with synthetic membranes and also exhibits cytotoxicity. Our studies demonstrated that glycation modification of IAPP promotes the amyloidogenic properties of IAPP, and it may play a role in accumulating additional amyloid during T2D progression.

Initial National Institute of Health Stroke Scale to Early Predict the Improvement of Swallowing in Patients with Acute Ischemic Stroke.

OBJECTIVES: To study the applicability of National Institutes of Health Stroke Scale (NIHSS) in early predicting the prognosis of poststroke dysphagia in an acute ward. METHODS: This is an observational retrospective cohort study including adult patients with ischemic stroke. Patients with various factors affecting swallowing were excluded to obtain a representative sample of 165 patients. The main outcome measure was the improvements of oral intake function. RESULTS: The scores of facial palsy (NIHSS item 4) (odds ratio [OR]: 0.484, 95% confidence interval [CI]: 0.279-0.838, P = .0096] and language/aphasia (NIHSS item 9) (OR: 0.562, 95% CI: 0.321-0.982, P = .0430) demonstrated significantly negative effects on the early improvement of dysphagia. Moreover, the improved patients had a 4.14-fold (95% CI: 2.53-11.23, P = .005) increased odds of returning home compared with nonimproved patients. CONCLUSIONS: Our findings provide evidence that early improvement of poststroke dysphagia was significantly associated with a favorable discharge destination and NIHSS items of facial palsy and language/aphasia can be used at the onset of stroke to identify dysphagic patients at risk of achieving limited improvement. These findings provide valuable prognostic indicators for clinicians to make a precise outcome prediction at very early stage.

The difference of surgical outcomes between manifest exotropia and esotropia.

PURPOSE: To determine the factors that affect ocular alignment and binocular sensory functions after strabismus surgery and compare surgical outcomes between manifest exotropia (XT) and esotropia (ET). METHODS: In a retrospective study, 41 XT and 17 ET patients who had undergone strabismus surgery were recruited. Information on type and duration of strabismus, age at onset of deviation and surgery, pre- and postoperative strabismus deviation angles, and binocular sensory functions including stereoacuity and macular fusion capacity was recorded. RESULTS: In all patients, the ocular alignment and binocular sensory functions improved with time following surgery. Residue strabismus deviation angles (≦ 10 prism diopters) at postoperative 1 month determined the final successful ocular alignment. In patients with final excellent binocular sensory functions, XT group restored macular fusion capacity and stereoacuity at postoperative 1 month, but ET group regained macular fusion capacity at postoperative 1 month and then restored stereoacuity at postoperative 3 months. Though XT patients showed better pre- and postoperative stereoacuity than ET patients, patients with successful ocular alignment had an odd of 4.5 in XT group and 22.5 in ET group to achieve excellent and fair binocular sensory functions. CONCLUSION: Surgical correction of strabismus could improve ocular alignment and binocular sensory functions in patients with manifest strabismus, regardless of onset age, strabismus duration, or type. Postoperative 1-month status may help to predict the final motor and sensory outcomes. ET patients would benefit more final successful ocular alignment and excellent binocular sensory functions from early surgery and maintaining postoperative small deviation angle than XT patients.

Stress Aggravates High-Fat-Diet-Induced Insulin Resistance via a Mechanism That Involves the Amygdala and Is Associated with Changes in Neuroplasticity.

BACKGROUND: The notion that exposure to chronic stress predisposes individuals to developing type 2 diabetes (T2D) has gained much attention in recent decades. Long-term stress induces neuroadaptation in the amygdala and increases corticosterone levels. Corticosterone, the major stress hormone in rodents, induces insulin resistance and obesity in mice. However, little is known about whether the stress-induced amygdalar neuroadaptation could promote the risk of T2D. METHODS: We used an 11-week high-fat diet (HFD) feeding paradigm to induce insulin dysfunction in mice, followed by implementation of a 10-day social defeat (SD) stress protocol. RESULTS: Mice receiving SD at the beginning of the HFD feeding aggravated HFD-induced insulin resistance and white adipose tissue expansion. HFD mice had higher levels of plasma corticosterone, which was not affected by the SD. The SD stress upregulated the expression of TrkB and synaptotagmin-4 in the amygdala of HFD mice. Bilateral lesions of the central amygdalae before SD stress inhibited the stress-induced aggravating effect without affecting the HFD-induced elevation of plasma corticosterone. CONCLUSIONS: Stress aggravates HFD-induced insulin resistance and neuroadaptation in the amygdala. The HFD-induced insulin resistance is amygdala-dependent. Understanding the role of stress-induced amygdalar adaptation in the development of T2D could inform therapies aimed at reducing chronic stressors to decrease the risk for T2D.

Microscopic evidence for the dissociation of water molecules on cleaved GaN(11[combining macron]00).

The dissociation of water molecules absorbed on a cleaved non-polar GaN(11[combining macron]00) surface was studied primarily with synchrotron-based photoemission spectra and density-functional-theory calculations. The adsorbed water molecules are spontaneously dissociated into hydrogen atoms and hydroxyl groups at either 300 or 130 K, which implies a negligible activation energy (<11 meV) for the dissociation. The produced H and OH were bound to the surface nitrogen and gallium on GaN(11[combining macron]00) respectively. These results highlight the promising applications of the non-polar GaN(11[combining macron]00) surface in water dissociation and hydrogen generation.

Functional engineered mesenchymal stem cells with fibronectin-gold composite coated catheters for vascular tissue regeneration.

Vascularization of engineered tissues remains one of the key problems. Here, we described a novel approach to promote vascularization of engineered tissues using fibronectin (FN) incorporated gold nanoparticles (AuNP) coated onto catheters with mesenchymal stem cells (MSCs) for tissue engineering. We found that the FN-AuNP composite with 43.5 ppm of AuNP exhibited better biomechanical properties and thermal stability than pure FN. FN-AuNP composites promoted MSC proliferation and increased the biocompatibility. Mechanistically, vascular endothelial growth factor (VEGF) promoted MSC migration on FN-AuNP through the endothelial oxide synthase (eNOS)/metalloproteinase (MMP) signaling pathway. Vascular femoral artery tissues isolated from the implanted FN-AuNP-coated catheters with MSCs expressed substantial CD31 and alpha-smooth muscle actin (α-SMA), displayed higher antithrombotic activity, as well as better endothelialization ability than those coated with all other materials. These data suggested that the implantation of FN-AuNP-coated catheter with MSCs could be a novel strategy for vascular biomaterials applications.

Correction of hyperopia with astigmatism following radial keratotomy with daily disposable plus spherical contact lens: a case report.

PURPOSE: To report the refractive correction in a case of hyperopia and astigmatism following radial keratotomy. METHODS: A case report. RESULTS: A 47-year-old woman, who had undergone refractive surgery for radial keratotomy in both eyes 22 years before the present study, presented to our clinic with blurred vision. Her best corrected visual acuity, with spectacle correction of +3.50 DS/-1.50 DCX130° in the right eye and +3.75 DS/-1.50 DCX80° in the left eye, was 0.2 logMAR and 0.3 logMAR, respectively. Her keratometric readings were 35.75 D/36.75 D at 74° and 35.25 D/36.25 D at 61°, respectively. Prompted by intolerance to glasses, the patient requested for contact lenses. First, we applied a rigid, gas-permeable contact lens. However, we noted poor fitting due to central corneal flattening. Subsequently, we applied a conventional plus spherical soft contact lens (PSSCL), which is thick in the center and can therefore correct hyperopia and low-grade astigmatism simultaneously. The conventional PSSCL showed slightly inferior decentration, with good movement, and the patient was satisfied with it. After ascertaining the patient's living habits, we decided that a daily disposable soft contact lens would most meet her needs. The final prescription was a daily disposable PSSCL; the patient was satisfied with her corrected visual acuity of 0.0 logMAR in the right eye and 0.0 logMAR in left eye. Her daily disposable PSSCL-corrected visual acuity was stable during the 10-month follow-up. CONCLUSION: For patients displaying hyperopia with astigmatism following radial keratotomy, the PSSCL may confer better corrected visual acuity and acceptability.

Factors associated with corneal epithelial defects after pars plana vitrectomy.

PURPOSE: To investigate the risk factors associated with corneal epithelial defects (CED) and delayed healing (exceeding 1 week) following pars plana vitrectomy (PPV). METHODS: This retrospective study enrolled patients who underwent PPV at a single center in Taiwan between 2011 and 2012. Medical records were reviewed, including demographic, underlying disease, surgical indication, operation parameters, and existence of CED. These data were statistically analyzed. All patients were evaluated during follow-ups at day 1 and week 1 after PPV. Patients with persistent CED 1 week after PPV were diagnosed with delayed healing. RESULTS: A total of 255 patients were included in the study, consisting of 139 men and 116 women, with a mean age of 56.9 years. PPV was performed under the indications of rhegmatogenous retinal detachment (RRD), diabetic retinopathy, or vitreoretinal interface disease. Out of 255 eyes, 59 developed CED 1 day after surgery (23.1%), and CED was associated with younger age, diabetes mellitus (DM), RRD, longer duration of surgery, and silicon oil use during surgery. Among them, seven patients (11.9%) demonstrated delayed healing, which was associated with a higher rate of DM (p = 0.085), compared to patients who healed within 1 week. CONCLUSION: Patients with RRD, longer duration of surgery, and DM may be at risk of developing CED after PPV. In addition, patients with DM demonstrated a higher incidence of delayed corneal healing.

Receptor-type tyrosine-protein phosphatase κ directly targets STAT3 activation for tumor suppression in nasal NK/T-cell lymphoma.

Nasal-type natural killer/T-cell lymphoma (NKTCL) is an aggressive disease characterized by frequent deletions on 6q, and constitutive activation of signal transducer and activator of transcription 3 (STAT3). Phosphorylation at Tyr705 activates STAT3, inducing dimerization, nuclear translocation, and DNA binding. In this study, we investigated whether receptor-type tyrosine-protein phosphatase κ (PTPRK), the only protein tyrosine phosphatase at 6q that contains a STAT3-specifying motif, negatively regulates STAT3 activation in NKTCL. PTPRK was highly expressed in normal NK cells but was underexpressed in 4 of 5 (80%) NKTCL cell lines and 15 of 27 (55.6%) primary tumors. Significantly, PTPRK protein expression was inversely correlated with nuclear phospho-STAT3(Tyr705) expression in NKTCL cell lines (P = .025) and tumors (P = .040). PTPRK restoration decreased nuclear phospho-STAT3(Tyr705) levels, whereas knockdown of PTPRK increased such levels in NKTCL cells. Phosphatase substrate-trapping mutant assays demonstrated the binding of PTPRK to STAT3, and phosphatase assays showed that PTPRK directly dephosphorylated phospho-STAT3(Tyr705). Restoration of PTPRK inhibited tumor cell growth and reduced the migration and invasion ability of NKTCL cells. Monoallelic deletion and promoter hypermethylation caused underexpression of PTPRK messenger RNA in NKTCL, and methylation of the PTPRK promoter significantly correlated with inferior overall survival (P = .049) in NKTCL patients treated with the steroid-dexamethasone, methotrexate, ifosfamide, l-asparaginase, and etoposide regimen. Altogether, our findings show that PTPRK underexpression leads to STAT3 activation and contributes to NKTCL pathogenesis.

Critical Roles of Dual-Specificity Phosphatases in Neuronal Proteostasis and Neurological Diseases.

Protein homeostasis or proteostasis is a fundamental cellular property that encompasses the dynamic balancing of processes in the proteostasis network (PN). Such processes include protein synthesis, folding, and degradation in both non-stressed and stressful conditions. The role of the PN in neurodegenerative disease is well-documented, where it is known to respond to changes in protein folding states or toxic gain-of-function protein aggregation. Dual-specificity phosphatases have recently emerged as important participants in maintaining balance within the PN, acting through modulation of cellular signaling pathways that are involved in neurodegeneration. In this review, we will summarize recent findings describing the roles of dual-specificity phosphatases in neurodegeneration and offer perspectives on future therapeutic directions.

Magnetite nanoparticle interactions with insulin amyloid fibrils.

Accumulation of amyloid fibrils is one of the likely key factors leading to the development of Alzheimer's disease and other amyloidosis associated diseases. Magnetic nanoparticles (NPs) have been developed as promising medical materials for many medical applications. In this study, we have explored the effects of Fe3O4 NPs on the fibrillogenesis process of insulin fibrils. When Fe3O4 NPs were co-incubated with insulin, Fe3O4 NPs had no effect on the structural transformation into amyloid-like fibrils but had higher affinity toward insulin fibrils. We demonstrated that the zeta potential of insulin fibrils and Fe3O4 NPs were both positive, suggesting the binding forces between Fe3O4 NPs and insulin fibrils were van der Waals forces but not surface charge. Moreover, a different amount of Fe3O4 NPs added had no effect on secondary structural changes of insulin fibrils. These results propose the potential use of Fe3O4 NPs as therapeutic agents against diseases related to protein aggregation or contrast agents for magnetic resonance imaging.

Glucose regulates amyloid ß production via AMPK.

Alzheimer's disease (AD) is the most common form of dementia in the elderly. Accumulation of Aß peptides in the brain has been suggested as the cause of AD (amyloid cascade hypothesis); however, the mechanism for the abnormal accumulation of Aß in the brains of AD patients remains unclear. A plethora of evidence has emerged to support a link between metabolic disorders and AD. This study was designed to examine the relationship between energy status and Aß production. Neuro 2a neuroblastoma cells overexpressing human amyloid precursor protein 695 (APP cells) were cultured in media containing different concentrations of glucose and agonist or antagonist of AMP-activated-protein-kinase (AMPK), a metabolic master sensor. The results showed that concentrations of glucose in the culture media were negatively associated with the activation statuses of AMPK in APP cells, but positively correlated with the levels of secreted Aß. Modulating AMPK activities affected the production of Aß. If APP cells were cultured in high glucose medium (i.e., AMPK was inactive), stimulation of AMPK activity decreased the production levels of Aß. On the contrary, if APP cells were incubated in medium containing no glucose (i.e., AMPK was activated), inhibition of AMPK activity largely increased Aß production. As AMPK activation is a common defect in metabolic abnormalities, our study supports the premise that metabolic disorders may aggravate AD pathogenesis.

The Fracture Risk of Elderly Patients With Atopic Dermatitis.

Background: A higher fracture risk has been reported previously in patients with atopic dermatitis (AD). The bone mineral density (BMD) was not accounted for in these studies. Objective: To investigate the fracture risk in AD patients after adjustment for factors including BMD. Methods: We retrospectively analyzed AD patients (≥45 years) who underwent BMD examination at our hospital from July 2010 to February 2023. Individuals who received BMD examinations during a health checkup were identified as the controls. We documented their clinical characteristics, BMD, 10-year risk for a major fracture based on FRAX (Fracture Risk Assessment Tool), and development of osteoporotic fractures. Patients were followed until development of new onset fracture or the end of the study period. A cross-sectional comparison of BMD between AD patients and controls at baseline was performed using the Mann-Whitney U test after propensity score matching (PSM). Their fracture risks were compared using the multivariate Cox regression model. BMD and fracture risk were also compared between AD patients who received systemic therapy and those who did not. Results: A total of 50 AD patients and 386 controls were enrolled. The median age was older in AD patients when compared with controls (70 years vs 60 years). Their BMD at all sites was similar after PSM. After a median follow-up of 1.7-2.0 years, 13 osteoporotic fractures were identified. In the multivariate Cox regression analysis, AD was not associated with new onset fractures of all sites (adjusted hazard ratio [aHR] 2.55, 95% confidence interval [CI] 0.72-9.01) but was significantly associated with new onset vertebral fractures (aHR 6.80, 95% CI 1.77-26.17). The BMD and incidence of fractures were similar between AD who received systemic therapy and those who did not. Conclusions: Elderly AD patients had similar BMD but a higher short-term risk for vertebral fractures when compared with the controls.