1. Epidemiology and Global Health
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Epidemiological transition to mortality and re-fracture following an initial fracture

  1. Thao Phuong Ho-Le  Is a corresponding author
  2. Thach Son Tran
  3. Dana Bliuc
  4. Hanh M Pham
  5. Steven A Frost
  6. Jacqueline R Center
  7. John A Eisman
  8. Tuan V Nguyen  Is a corresponding author
  1. Garvan Institute of Medical Research, Australia
  2. Andrology and Fertility Hospital of Hanoi, Viet Nam
Research Article
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Cite this article as: eLife 2021;10:e61142 doi: 10.7554/eLife.61142

Abstract

This study sought to redefine the concept of fracture risk that includes refracture and mortality. We analysed data obtained from 2046 women and 1205 men aged 60+ years, whose health status, including bone mineral density (BMD), has been monitored. During the 20-year follow-up period, among 632 women and 184 men with a first incident fracture, the risk of sustaining a second fracture was higher in women (36%, n=229) than in men (22%, n=41), but mortality risk was higher in men (41%, n=75) than in women (25%, n=156). Key predictors of subsequent fracture risk included advancing age (hazard ratio [HR] 1.17; 95%CI, 1.08-1.26) and low BMD (HR 1.41; 1.23-1.61). Predictors of mortality were male gender (HR 2.4; 1.79-3.21), advancing age (1.67; 1.53-1.83), and lower femoral neck BMD (1.16; 1.01-1.33). These results were incorporated into a prediction model to aid patient-doctor discussion about fracture vulnerability and treatment decisions.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for Figures 3, Figure 3 - figure supplement 1, and Figure 3 - figure supplement 2.

Article and author information

Author details

  1. Thao Phuong Ho-Le

    Healthy Aging Theme, Garvan Institute of Medical Research, Sydney, Australia
    For correspondence
    t.ho-le@garvan.org.au
    Competing interests
    Thao Phuong Ho-Le, received the Christine & T. Jack Martin Research travel grant from AMGEN & Australian and New Zealand Bone and Mineral Society..
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8387-1893
  2. Thach Son Tran

    Healthy Aging Theme, Garvan Institute of Medical Research, Sydney, Australia
    Competing interests
    No competing interests declared.
  3. Dana Bliuc

    Healthy Aging Theme, Garvan Institute of Medical Research, Sydney, Australia
    Competing interests
    No competing interests declared.
  4. Hanh M Pham

    Fertility Department, Andrology and Fertility Hospital of Hanoi, Hanoi, Viet Nam
    Competing interests
    No competing interests declared.
  5. Steven A Frost

    Healthy Aging Theme, Garvan Institute of Medical Research, Sydney, Australia
    Competing interests
    No competing interests declared.
  6. Jacqueline R Center

    Healthy Aging Theme, Garvan Institute of Medical Research, Sydney, Australia
    Competing interests
    Jacqueline R Center, has given educational talks for and received travel expenses from Amgen, Merck Sharp & Dohme, Novartis, Sanofi-Aventis. She has received travel expenses from Merck Sharp & Dohme, Amgen and Aspen..
  7. John A Eisman

    Healthy Aging Theme, Garvan Institute of Medical Research, Sydney, Australia
    Competing interests
    John A Eisman, has served as consultant on Scientific Advisory Boards for Amgen, 35 Eli Lilly, Merck Sharp & Dohme, Novartis, Sanofi-Aventis, Servier and deCode..
  8. Tuan V Nguyen

    Healthy Aging Theme, Garvan Institute of Medical Research, Sydney, Australia
    For correspondence
    t.nguyen@garvan.org.au
    Competing interests
    Tuan V Nguyen, has received honoraria for consulting and speaking in symposia sponsored by Merck Sharp & Dohme, Roche, Sanofi-Aventis, Novartis, and Bridge Healthcare Pty Ltd (Vietnam)..

Funding

National Health and Medical Research Council (The Australian National Health and Medical Research Council grant,NHMRC 276413)

  • Tuan V Nguyen

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Human subjects: The study was approved by the Ethics Committee of St Vincent's Hospital (Sydney) (HREC reference number: 13/254) and carried out according to the Australian National Health and Medical Research Council (NHMRC) Guidelines, consistent with the Declaration of Helsinki (established in 1964 and revised in 1989) (US Food and Drug Administration). All participants have provided written informed consent.

Reviewing Editor

  1. Dolores Shoback, University of California, San Francisco, United States

Publication history

  1. Received: July 16, 2020
  2. Accepted: January 25, 2021
  3. Accepted Manuscript published: February 9, 2021 (version 1)
  4. Version of Record published: March 2, 2021 (version 2)

Copyright

© 2021, Ho-Le et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Further reading

Further reading

    1. Epidemiology and Global Health
    2. Immunology and Inflammation
    Yansheng Li et al.
    Research Article Updated

    Influenza pandemics pose public health threats annually for lacking vaccine that provides cross-protection against novel and emerging influenza viruses. Combining conserved antigens that induce cross-protective antibody responses with epitopes that activate cross-protective T cell responses might be an attractive strategy for developing a universal vaccine. In this study, we constructed a recombinant protein named NMHC that consists of influenza viral conserved epitopes and a superantigen fragment. NMHC promoted the maturation of bone marrow-derived dendritic cells and induced CD4+ T cells to differentiate into Th1, Th2, and Th17 subtypes. Mice vaccinated with NMHC produced high levels of immunoglobulins that cross-bound to HA fragments from six influenza virus subtypes with high antibody titers. Anti-NMHC serum showed potent hemagglutinin inhibition effects to highly divergent group 1 (H1 subtype) and group 2 (H3 subtype) influenza virus strains. Furthermore, purified anti-NMHC antibodies bound to multiple HAs with high affinities. NMHC vaccination effectively protected mice from infection and lung damage when exposed to two subtypes of H1N1 influenza virus. Moreover, NMHC vaccination elicited CD4+ and CD8+ T cell responses that cleared the virus from infected tissues and prevented virus spread. In conclusion, this study provides proof of concept that NMHC vaccination triggers B and T cell immune responses against multiple influenza virus infections. Therefore, NMHC might be a candidate universal broad-spectrum vaccine for the prevention and treatment of multiple influenza viruses.

    1. Epidemiology and Global Health
    2. Microbiology and Infectious Disease
    Mark Ferris et al.
    Research Advance Updated

    Background:

    Respiratory protective equipment recommended in the UK for healthcare workers (HCWs) caring for patients with COVID-19 comprises a fluid-resistant surgical mask (FRSM), except in the context of aerosol generating procedures (AGPs). We previously demonstrated frequent pauci- and asymptomatic severe acute respiratory syndrome coronavirus 2 infection HCWs during the first wave of the COVID-19 pandemic in the UK, using a comprehensive PCR-based HCW screening programme (Rivett et al., 2020; Jones et al., 2020).

    Methods:

    Here, we use observational data and mathematical modelling to analyse infection rates amongst HCWs working on ‘red’ (coronavirus disease 2019, COVID-19) and ‘green’ (non-COVID-19) wards during the second wave of the pandemic, before and after the substitution of filtering face piece 3 (FFP3) respirators for FRSMs.

    Results:

    Whilst using FRSMs, HCWs working on red wards faced an approximately 31-fold (and at least fivefold) increased risk of direct, ward-based infection. Conversely, after changing to FFP3 respirators, this risk was significantly reduced (52–100% protection).

    Conclusions:

    FFP3 respirators may therefore provide more effective protection than FRSMs for HCWs caring for patients with COVID-19, whether or not AGPs are undertaken.

    Funding:

    Wellcome Trust, Medical Research Council, Addenbrooke’s Charitable Trust, NIHR Cambridge Biomedical Research Centre, NHS Blood and Transfusion, UKRI.