Predicting Fracture Risk in Younger Postmenopausal Women: Comparison of the Garvan and FRAX Risk Calculators in the Women’s Health Initiative Study
Guidelines recommend fracture risk assessment in postmenopausal women aged 50–64, but the optimal method is unknown.
To compare discrimination and calibration of the Fracture Risk Assessment Tool (FRAX) and Garvan fracture risk calculator for predicting fractures in postmenopausal women aged 50–64 at baseline.
Prospective observational study.
Sixty-three thousand seven hundred twenty-three postmenopausal women aged 50–64 years participating in the Women’s Health Initiative Observational Study and Clinical Trials.
Incident hip fractures and major osteoporotic fractures (MOF) during 10-year follow-up. Calculated FRAX- and Garvan-predicted hip fracture and MOF fracture probabilities.
The observed 10-year hip fracture probability was 0.3% for women aged 50–54 years (n = 14,768), 0.6% for women aged 55–59 years (n = 22,442), and 1.1% for women aged 60–64 years (n = 25,513). At sensitivity thresholds ≥ 80%, specificity of both tools for detecting incident hip fracture during 10 years of follow-up was low: Garvan 30.6% (95% confidence interval [CI] 30.3–31.0%) and FRAX 43.1% (95% CI 42.7–43.5%). At maximal area under the receiver operating characteristic curve (AUC(c), 0.58 for Garvan, 0.65 for FRAX), sensitivity was 16.0% (95% CI 12.7–19.4%) for Garvan and 59.2% (95% CI 54.7–63.7%) for FRAX. At AUC(c) values, sensitivity was lower in African American and Hispanic women than among white women and lower in women aged 50–54 than those 60–64 years old. Observed hip fracture probabilities were similar to FRAX-predicted probabilities but greater than Garvan-predicted probabilities. At AUC(c) values (0.56 for both tools), sensitivity for identifying MOF was also low (range 26.7–46.8%). At AUC(c) values (0.55 for both tools), sensitivity for identifying any clinical fracture ranged from 18.1 to 34.0%.
In postmenopausal women aged 50–64 years, the FRAX and Garvan fracture risk calculator discriminate poorly between women who do and do not experience fracture during 10-year follow-up. There is no useful threshold for either tool.
KEY WORDSGarvan fracture osteoporosis FRAX fracture risk assessment
Short List of WHI Investigators
Program Office: (National Heart, Lung, and Blood Institute, Bethesda, MA) Jacques Rossouw, Shari Ludlam, Joan McGowan, Leslie Ford, and Nancy Geller.
Clinical Coordinating Center: Clinical Coordinating Center: (Fred Hutchinson Cancer Research Center, Seattle, WA) Garnet Anderson, Ross Prentice, Andrea LaCroix, and Charles Kooperberg.
Investigators and Academic Centers: (Brigham and Women’s Hospital, Harvard Medical School, Boston, MA) JoAnn E. Manson; (MedStar Health Research Institute/Howard University, Washington, DC) Barbara V. Howard; (Stanford Prevention Research Center, Stanford, CA) Marcia L. Stefanick; (The Ohio State University, Columbus, OH) Rebecca Jackson; (University of Arizona, Tucson/Phoenix, AZ) Cynthia A. Thomson; (University at Buffalo, Buffalo, NY) Jean Wactawski-Wende; (University of Florida, Gainesville/Jacksonville, FL) Marian Limacher; (University of Iowa, Iowa City/Davenport, IA) Jennifer Robinson; (University of Pittsburgh, Pittsburgh, PA) Lewis Kuller; (Wake Forest University School of Medicine, Winston-Salem, NC) Sally Shumaker; (University of Nevada, Reno, NV) Robert Brunner; (University of Minnesota, Minneapolis, MN) Karen L. Margolis.
Women’s Health Initiative Memory Study: (Wake Forest University School of Medicine, Winston-Salem, NC) Mark Espeland.
For a list of all the investigators who have contributed to WHI science, please visit: https://www.whi.org/researchers/Documents%20%20Write%20a%20Paper/WHI%20Investigator%20Long%20List.pdf
We thank the WHI study participants and investigators for their tremendous dedication and commitment to the study.
CJC was responsible for the conception of the study. All authors participated in the analysis and interpretation of data and critical revisions of the manuscript for important intellectual content. JL was responsible for performing the statistical analyses. AL, JAC, MSL, and JEM were responsible for acquisition of data.
The WHI program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services through contracts HHSN268201600018C, HHSN268201600001C, HHSN268201600002C, HHSN268201600003C, and HHSN268201600004C.
Compliance with Ethical Standards
Human subjects review committees at each participating institution approved the study. Each participant provided written informed consent.
Conflict of Interest
The authors declare that they do not have a conflict of interest.
JL had full access to all the data in the study and takes responsibility for the integrity of the data analysis.
Women’s Health Initiative Study data are available via the BioLINCC website of the National Heart, Lung, and Blood Institute at https://biolincc.nhlbi.nih.gov/home/
Role of the Funding Source
This study was partially funded through contracts with the WHI Coordinating Center. The WHI Study was funded by the National Institutes of Health. The National Institutes of Health designated representatives who participated in the design and monitoring of the WHI. The researchers are independent from the funders.
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