1. Epidemiology and Global Health

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
https://doi.org/10.7554/eLife.61142
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Cite this article
  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
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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.

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  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

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Further reading

    1. Epidemiology and Global Health

    ‘Skeletal Age’ for mapping the impact of fracture on mortality

    Thach Tran, Thao Ho-Le ... Tuan V Nguyen
    Research Article

    Background:

    Fragility fracture is associated with an increased risk of mortality, but mortality is not part of doctor-patient communication. Here, we introduce a new concept called ‘Skeletal Age’ as the age of an individual’s skeleton resulting from a fragility fracture to convey the combined risk of fracture and fracture-associated mortality for an individual.

    Methods:

    We used the Danish National Hospital Discharge Register which includes the whole-country data of 1,667,339 adults in Denmark born on or before January 1, 1950, who were followed up to December 31, 2016 for incident low-trauma fracture and mortality. Skeletal age is defined as the sum of chronological age and the number of years of life lost (YLL) associated with a fracture. Cox’s proportional hazards model was employed to determine the hazard of mortality associated with a specific fracture for a given risk profile, and the hazard was then transformed into YLL using the Gompertz law of mortality.

    Results:

    During the median follow-up period of 16 years, there had been 307,870 fractures and 122,744 post-fracture deaths. A fracture was associated with between 1 and 7 years of life lost, with the loss being greater in men than women. Hip fractures incurred the greatest loss of life years. For instance, a 60-year-old individual with a hip fracture is estimated to have a skeletal age of 66 for men and 65 for women. Skeletal Age was estimated for each age and fracture site stratified by gender.

    Conclusions:

    We propose ‘Skeletal Age’ as a new metric to assess the impact of a fragility fracture on an individual’s life expectancy. This approach will enhance doctor-patient risk communication about the risks associated with osteoporosis.

    Funding:

    National Health and Medical Research Council in Australia and Amgen Competitive Grant Program 2019.

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    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.

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