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.

Reviewing Editor

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

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.

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

Share this article

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
    2. Microbiology and Infectious Disease
    Patrick E Brown, Sze Hang Fu ... Ab-C Study Collaborators
    Research Article Updated

    Background:

    Few national-level studies have evaluated the impact of ‘hybrid’ immunity (vaccination coupled with recovery from infection) from the Omicron variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

    Methods:

    From May 2020 to December 2022, we conducted serial assessments (each of ~4000–9000 adults) examining SARS-CoV-2 antibodies within a mostly representative Canadian cohort drawn from a national online polling platform. Adults, most of whom were vaccinated, reported viral test-confirmed infections and mailed self-collected dried blood spots (DBSs) to a central lab. Samples underwent highly sensitive and specific antibody assays to spike and nucleocapsid protein antigens, the latter triggered only by infection. We estimated cumulative SARS-CoV-2 incidence prior to the Omicron period and during the BA.1/1.1 and BA.2/5 waves. We assessed changes in antibody levels and in age-specific active immunity levels.

    Results:

    Spike levels were higher in infected than in uninfected adults, regardless of vaccination doses. Among adults vaccinated at least thrice and infected more than 6 months earlier, spike levels fell notably and continuously for the 9-month post-vaccination. In contrast, among adults infected within 6 months, spike levels declined gradually. Declines were similar by sex, age group, and ethnicity. Recent vaccination attenuated declines in spike levels from older infections. In a convenience sample, spike antibody and cellular responses were correlated. Near the end of 2022, about 35% of adults above age 60 had their last vaccine dose more than 6 months ago, and about 25% remained uninfected. The cumulative incidence of SARS-CoV-2 infection rose from 13% (95% confidence interval 11–14%) before omicron to 78% (76–80%) by December 2022, equating to 25 million infected adults cumulatively. However, the coronavirus disease 2019 (COVID-19) weekly death rate during the BA.2/5 waves was less than half of that during the BA.1/1.1 wave, implying a protective role for hybrid immunity.

    Conclusions:

    Strategies to maintain population-level hybrid immunity require up-to-date vaccination coverage, including among those recovering from infection. Population-based, self-collected DBSs are a practicable biological surveillance platform.

    Funding:

    Funding was provided by the COVID-19 Immunity Task Force, Canadian Institutes of Health Research, Pfizer Global Medical Grants, and St. Michael’s Hospital Foundation. PJ and ACG are funded by the Canada Research Chairs Program.