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

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

Version 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.

Metrics

  • 1,690
    Page views
  • 190
    Downloads
  • 8
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Thao Phuong Ho-Le
  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
(2021)
Epidemiological transition to mortality and re-fracture following an initial fracture
eLife 10:e61142.
https://doi.org/10.7554/eLife.61142

Further reading

    1. Epidemiology and Global Health
    2. Medicine
    Jane A Cauley, Dolores M Shoback
    Insight

    More informed discussions between physicians and older adults about the consequences of an initial osteoporotic fracture could encourage more patients to consider treatments that protect against future fracture.

    1. Epidemiology and Global Health
    C Kim, Benjamin Chen ... RECOVER Mechanistic Pathways Task Force
    Review Article

    The NIH-funded RECOVER study is collecting clinical data on patients who experience a SARS-CoV-2 infection. As patient representatives of the RECOVER Initiative’s Mechanistic Pathways task force, we offer our perspectives on patient motivations for partnering with researchers to obtain results from mechanistic studies. We emphasize the challenges of balancing urgency with scientific rigor. We recognize the importance of such partnerships in addressing post-acute sequelae of SARS-CoV-2 infection (PASC), which includes ‘long COVID,’ through contrasting objective and subjective narratives. Long COVID’s prevalence served as a call to action for patients like us to become actively involved in efforts to understand our condition. Patient-centered and patient-partnered research informs the balance between urgency and robust mechanistic research. Results from collaborating on protocol design, diverse patient inclusion, and awareness of community concerns establish a new precedent in biomedical research study design. With a public health matter as pressing as the long-term complications that can emerge after SARS-CoV-2 infection, considerate and equitable stakeholder involvement is essential to guiding seminal research. Discussions in the RECOVER Mechanistic Pathways task force gave rise to this commentary as well as other review articles on the current scientific understanding of PASC mechanisms.