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Open Access 26-07-2023 | Osteoporosis | Original Article

A genome-wide genomic score added to standard recommended stratification tools does not improve the identification of patients with very low bone mineral density

Authors: J. Therkildsen, P.D. Rohde, L. Nissen, J. Thygesen, E.-M. Hauge, B.L. Langdahl, M. Boettcher, M. Nyegaard, S. Winther

Published in: Osteoporosis International | Issue 11/2023

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Abstract

Summary

The role of integrating genomic scores (GSs) needs to be assessed. Adding a GS to recommended stratification tools does not improve the prediction of very low bone mineral density. However, we noticed that the GS performed equally or above individual risk factors in discrimination.

Purpose

We aimed to investigate whether adding a genomic score (GS) to recommended stratification tools improves the discrimination of participants with very low bone mineral density (BMD).

Methods

BMD was measured in three thoracic vertebrae using CT. All participants provided information on standard osteoporosis risk factors. GSs and FRAX scores were calculated. Participants were grouped according to mean BMD into very low (<80 mg/cm3), low (80–120 mg/cm3), and normal (>120 mg/cm3) and according to the Bone Health and Osteoporosis Foundation recommendations for BMD testing into an “indication for BMD testing” and “no indication for BMD testing” group. Different models were assessed using the area under the receiver operating characteristics curves (AUC) and reclassification analyses.

Results

In the total cohort (n=1421), the AUC for the GS was 0.57 (95% CI 0.52–0.61) corresponding to AUCs for osteoporosis risk factors. In participants without indication for BMD testing, the AUC was 0.60 (95% CI 0.52–0.69) above or equal to AUCs for osteoporosis risk factors. Adding the GS to a clinical risk factor (CRF) model resulted in AUCs not statistically significant from the CRF model. Using probability cutoff values of 6, 12, and 24%, we found no improved reclassification or risk discrimination using the CRF-GS model compared to the CRF model.

Conclusion

Our results suggest adding a GS to a CRF model does not improve prediction. However, we noticed that the GS performed equally or above individual risk factors in discrimination. Clinical risk factors combined showed superior discrimination to individual risk factors and the GS, underlining the value of combined CRFs in routine clinics as a stratification tool.
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Metadata
Title
A genome-wide genomic score added to standard recommended stratification tools does not improve the identification of patients with very low bone mineral density
Authors
J. Therkildsen
P.D. Rohde
L. Nissen
J. Thygesen
E.-M. Hauge
B.L. Langdahl
M. Boettcher
M. Nyegaard
S. Winther
Publication date
26-07-2023
Publisher
Springer London
Published in
Osteoporosis International / Issue 11/2023
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI
https://doi.org/10.1007/s00198-023-06857-w

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