• Login
    View Item 
    •   Home
    • UMass Chan Faculty and Staff Research and Publications
    • UMass Chan Faculty and Researcher Publications
    • View Item
    •   Home
    • UMass Chan Faculty and Staff Research and Publications
    • UMass Chan Faculty and Researcher Publications
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of eScholarship@UMassChanCommunitiesPublication DateAuthorsUMass Chan AffiliationsTitlesDocument TypesKeywordsThis CollectionPublication DateAuthorsUMass Chan AffiliationsTitlesDocument TypesKeywords

    My Account

    LoginRegister

    Help

    AboutSubmission GuidelinesData Deposit PolicySearchingAccessibilityTerms of UseWebsite Migration FAQ

    Statistics

    Most Popular ItemsStatistics by CountryMost Popular Authors

    Re-evaluating osteoporosis and fracture risk in Crohn's disease patients in the era of TNF-alpha inhibitors

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Authors
    Hakimian, Shahrad
    Kheder, Joan
    Arum, Seth M.
    Cave, David R.
    Hyatt, Benjamin
    UMass Chan Affiliations
    Division of Endocrinology and Metabolism, Department of Medicine
    Division of Gastroenterology, Department of Medicine
    Document Type
    Journal Article
    Publication Date
    2018-02-01
    Keywords
    Adult
    Aged
    Bone Density
    Crohn Disease
    Female
    Fractures, Bone
    Humans
    Male
    Massachusetts
    Middle Aged
    Osteoporosis
    Retrospective Studies
    Risk Factors
    Tumor Necrosis Factor-alpha
    Vitamin D
    Crohn’s disease
    Osteoporosis
    anti-TNF medications
    Digestive System Diseases
    Gastroenterology
    Musculoskeletal Diseases
    Show allShow less
    
    Metadata
    Show full item record
    Link to Full Text
    https://doi.org/10.1080/00365521.2017.1416161
    Abstract
    INTRODUCTION: Patients with Crohn's disease (CD) are at increased risk for osteoporosis and fractures as compared to the general population. Recently, various cytokines including tumor necrosis factor (TNF)-alpha are found to play a major role in bone health. In this study, we aimed to gain a better understanding of the risk factors for osteoporosis and vitamin D deficiency in the era of TNF-alpha inhibitors. METHODS: We conducted a retrospective review of 464 consecutive patients with CD in our GI clinic between 2008 and 2015. Statistical analysis was performed using the student t-test and chi-square test. RESULTS: CD patients treated with TNF-alpha inhibitors (TNF) and those who are anti-TNF naïve (NB) had similar rates of vitamin D deficiency, insufficiency and normal vitamin D-25-OH levels. Similarly, rates of osteoporosis (16% vs 18%), osteopenia (53% vs 57%) and normal bone density (31% vs 25%) were comparable between the TNF and NB groups respectively. However, Z-scores at the spine (-0.47 vs -0.05) were significantly lower in the TNF group (p = .03). Interestingly, rates of osteoporosis in the NB group were drastically different before and after age 60 (3.6% vs 30%) with no major difference in the TNF group (15% vs 18%). Bone density was positively correlated with BMI (Pearson's R = 0.39) and negatively correlated with age and smoking status (R= -0.25). CONCLUSIONS: TNF group patients were diagnosed with osteoporosis from an earlier age compared to NB group but with a smaller increase in osteoporosis after menopause. Further prospective studies are necessary to further determine the role of anti-TNF medications in osteoporosis.
    Source

    Scand J Gastroenterol. 2018 Feb;53(2):168-172. doi: 10.1080/00365521.2017.1416161. Epub 2017 Dec 13. Link to article on publisher's website

    DOI
    10.1080/00365521.2017.1416161
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/46407
    PubMed ID
    29235392
    Related Resources

    Link to article in PubMed

    ae974a485f413a2113503eed53cd6c53
    10.1080/00365521.2017.1416161
    Scopus Count
    Collections
    UMass Chan Faculty and Researcher Publications

    entitlement

    Related items

    Showing items related by title, author, creator and subject.

    • Thumbnail

      Role of WFS1 in Regulating Endoplasmic Reticulum Stress Signaling: A Dissertation

      Fonseca, Sonya G. (2009-02-24)
      The endoplasmic reticulum (ER) is a multi-functional cellular compartment that functions in protein folding, lipid biosynthesis, and calcium homeostasis. Perturbations to ER function lead to the dysregulation of ER homeostasis, causing the accumulation of unfolded and misfolded proteins in the cell. This is a state of ER stress. ER stress elicits a cytoprotective, adaptive signaling cascade to mitigate stress, the Unfolded Protein Response (UPR). As long as the UPR can moderate stress, cells can produce the proper amount of proteins and maintain a state of homeostasis. If the UPR, however, is dysfunctional and fails to achieve this, cells will undergo apoptosis. Diabetes mellitus is a group of metabolic disorders characterized by persistent high blood glucose levels. The pathogenesis of this disease involves pancreatic β-cell dysfunction: an abnormality in the primary function of the β-cell, insulin production and secretion. Activation of the UPR is critical to pancreatic β-cell survival, where a disruption in ER stress signaling can lead to cell death and consequently diabetes. There are several models of ER stress leading to diabetes. Wolcott-Rallison syndrome, for example, occurs when there is a mutation in the gene encoding one of the master regulators of the UPR, PKR-like ER kinase (PERK). In this dissertation, we show that Wolfram Syndrome 1 (WFS1), an ER transmembrane protein, is a component of the UPR and is a downstream target of two of the master regulators of the UPR, Inositol Requiring 1 (IRE1) and PERK. WFS1 mutations lead to Wolfram syndrome, a non-autoimmune form of type 1 diabetes accompanied by optical atrophy and other neurological disorders. It has been shown that patients develop diabetes due to the selective loss of their pancreatic β-cells. Here we define the underlying molecular mechanism of β-cell loss in Wolfram syndrome, and link this cell loss to ER stress and a dysfunction in a component of the UPR, WFS1. We show that WFS1 expression is localized to the β-cell of the pancreas, it is upregulated during insulin secretion and ER stress, and its inactivation leads to chronic ER stress and apoptosis. This dissertation also reveals the previously unknown function of WFS1 in the UPR. Positive regulation of the UPR has been extensively studied, however, the precise mechanisms of negative regulation of this signaling pathway have not. Here we report that WFS1 regulates a key transcription factor of the UPR, activating transcription factor 6 (ATF6), through the ubiquitin-proteasome pathway. WFS1 expression decreases expression levels of ATF6 target genes and represses ATF6-mediated activation of the ER stress response (ERSE) promoter. WFS1 recruits and stabilizes an E3 ubiquitin ligase, HMG-CoA reductase degradation protein 1 (HRD1), on the ER membrane. The WFS1-HRD1 complex recruits ATF6 to the proteasome and enhances its ubiquitination and proteasome-mediated degradation, leading to suppression of the UPR under non-stress conditions. In response to ER stress, ATF6 is released from WFS1 and activates the UPR to mitigate ER stress. This body of work reveals a novel role for WFS1 in the UPR, and a novel mechanism for regulating ER stress signaling. These findings also indicate that hyperactivation of the UPR can lead to cellular dysfunction and death. This supports the notion that tight regulation of ER stress signaling is crucial to cell survival. This unanticipated role of WFS1 for a feedback loop of the UPR is relevant to diseases caused by chronic hyperactivation of ER stress signaling network such as pancreatic β-cell death in diabetes and neurodegeneration.
    • Thumbnail

      COVID-19: Pathophysiology and implications for cystic fibrosis, diabetes and cystic fibrosis-related diabetes

      Mason, Kelly; Hasan, Sana; Darukhanavala, Amy; Kutney, Katherine (2021-12-01)
      The novel SARS-CoV-2 coronavirus (COVID-19) has become a global health crisis since its initial outbreak in Wuhan, China in December 2019. On January 30, 2020, the WHO recognized the COVID-19 outbreak as a Public Health Emergency, and on March 11, 2020, it was declared a pandemic. Although all age groups have been affected, patients with cystic fibrosis (CF) and patients with type 1 or type 2 diabetes have been categorized as highly vulnerable to SARS-CoV-2 infection. Thus far, studies have found that the incidence of SARS-CoV-2 in the CF population is lower than the general population. We review the underlying protective mechanisms which may reduce inflammation and lung damage in CF patients, thus decreasing their risk of severe COVID-19. While the effect of SARS-CoV-2 in those with diabetes related to CF is unknown, other forms of diabetes have been associated with more severe disease. To further understand the potential impact of SARS-CoV-2 in cystic fibrosis-related diabetes, we provide a comprehensive overview of the potential factors contributing to COVID-19 severity in other forms of diabetes, including direct viral effect on the pancreas and indirect effects related to hyperglycemia and immune dysregulation.
    • Thumbnail

      Gaucher disease in the COVID-19 pandemic environment: The good, the bad and the unknown

      Ginns, Edward I.; Ryan, Emory; Sidransky, Ellen (2021-04-01)
      Early in the course of the novel coronavirus disease 2019 (COVID-19) pandemic, the rare disease community anticipated that patients with lysosomal and other metabolic disorders would be at increased risk for poor disease outcomes and mortality from the SARS-CoV-2 virus.
    DSpace software (copyright © 2002 - 2023)  DuraSpace
    Lamar Soutter Library, UMass Chan Medical School | 55 Lake Avenue North | Worcester, MA 01655 USA
    Quick Guide | escholarship@umassmed.edu
    Open Repository is a service operated by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.