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Performance of FRAX in older adults with frailty: the Framingham Heart Study

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Abstract

Summary

We compared the performance of FRAX according to frailty status in 3554 individuals from the Framingham Study. During 10-year follow-up, 6.9% and 3.0% of participants with and without frailty experienced MOF. Discrimination profiles were lower in participants with frailty compared to those without, but they improved when FRAX included BMD.

Introduction

Frailty increases fracture risk. FRAX was developed to predict fractures but never validated in individuals with frailty. We aimed to compare the predictive performance of FRAX (v4.3) in individuals with and without frailty.

Methods

We conducted a cohort study using the Framingham Heart Study. Frailty was defined by the Fried phenotype. Major osteoporotic fractures (MOF) were ascertained from medical records during 10-year follow-up. To evaluate discrimination and calibration of FRAX, we calculated the area-under-the-receiver-operating characteristics curves (AUC) using logistic regression models and observed-to-predicted fracture probabilities. Analyses were stratified by frailty status.

Results

Frailty was present in 550/3554 (15.5%) of participants. Participants with frailty were older (81.1 vs. 67.6 years), female (68.6% vs. 55.1%), and had greater mean FRAX scores (MOF: 15.9% vs. 10.1%) than participants without frailty. During follow-up, 38 participants with frailty (6.9%) and 91 without (3.0%) had MOFs. The AUC for FRAX (without BMD) was lower in participants with frailty (0.584; 95% CI 0.504–0.663) compared to those without (0.695; 95% CI 0.649–0.741); p value = 0.02. Among participants with frailty, the AUC improved when FRAX included BMD (AUC 0.658, p value < 0.01). FRAX overestimated MOF risk, with larger overestimations in individuals without frailty. Performance of FRAX for hip fracture was similar.

Conclusion

FRAX may have been less able to identify frail individuals at risk for fracture, as compared with individuals without frailty, unless information on BMD is available. This suggests that BMD captures features important for fracture prediction in frail persons. Future fracture prediction models should be developed among persons with frailty.

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Acknowledgements

We wanted to specifically acknowledge Dr. Natalia A. Gouskova for her input on the measures of AUC comparisons.

Funding

This work was supported by the National Institute of Health, National Institute on Aging (NIA), K24 AG070106, and the National Institute of Arthritis Musculoskeletal and Skin Diseases R01 AR041398. We would like to refer to the Framingham contract acknowledgment: National Heart, Lung and Blood Institute’s Framingham Heart Study (Contract No. HHSN268201500001I).

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Authors and Affiliations

  1. Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Nakhon Pathom, Thailand

    Tanchanok Chattaris

  2. Hinda and Arthur Marcus Institute for Aging Research and Department of Medicine, Hebrew SeniorLife, 1200 Centre Street, Boston, MA, 02131, USA

    Tanchanok Chattaris, Laiji Yang, Shivani Sahni, Elizabeth J. Samelson, Douglas P. Kiel & Sarah D. Berry

  3. The University of Sheffield, Sheffield, UK

    Helena Johansson

  4. Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA

    Shivani Sahni, Elizabeth J. Samelson, Douglas P. Kiel & Sarah D. Berry

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Correspondence to Sarah D. Berry.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Conflicts of interest

SS has institutional grants from Solarea Bio Inc., has reviewed grants for the American Egg Board’s Egg Nutrition Center and National Dairy Council, and was a scientific advisor to Institute for the Advancement of Food and Nutrition Sciences (ended 2022). EJS has received funding for her institution from Amgen. DPK acted as a data safety monitoring board member for Agnovos and a scientific advisory board member for Solarea Bio, Reneo, and Pfizer. DPK received grants from Amgen and Solarea Bio. DPK and SDB received royalties from Wolters Kluwer.

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Chattaris, T., Yang, L., Johansson, H. et al. Performance of FRAX in older adults with frailty: the Framingham Heart Study. Osteoporos Int 35, 265–275 (2024). https://doi.org/10.1007/s00198-023-06950-0

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  • DOI: https://doi.org/10.1007/s00198-023-06950-0

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