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. 2020 Feb 12;9(2):499.
doi: 10.3390/jcm9020499.

Evaluating the Performance of the WHO International Reference Standard for Osteoporosis Diagnosis in Postmenopausal Women of Varied Polygenic Score and Race

Qing Wu  1   2 , Xiangxue Xiao  1   2 , Yingke Xu  1   2
Affiliations

Evaluating the Performance of the WHO International Reference Standard for Osteoporosis Diagnosis in Postmenopausal Women of Varied Polygenic Score and Race

Qing Wu et al. J Clin Med. .

Abstract

Background: Whether the bone mineral density (BMD) T-score performs differently in osteoporosis classification in women of different genetic profiling and race background remains unclear.

Methods: The genomic data in the Women's Health Initiative study was analyzed (n = 2417). The polygenic score (PGS) was calculated from 63 BMD-associated single nucleotide polymorphisms (SNPs) for each participant. The World Health Organization's (WHO) definition of osteoporosis (BMD T-score ≤-2.5) was used to estimate the cumulative incidence of fracture.

Results: T-score classification significantly underestimated the risk of major osteoporotic fracture (MOF) in the WHI study. An enormous underestimation was observed in African American women (POR: 0.52, 95% CI: 0.30-0.83) and in women with low PGS (predicted/observed ratio [POR]: 0.43, 95% CI: 0.28-0.64). Compared to Caucasian women, African American, African Indian, and Hispanic women respectively had a 59%, 41%, and 55% lower hazard of MOF after the T-score was adjusted for. The results were similar when used for any fractures.

Conclusions: Our study suggested the BMD T-score performance varies significantly by race in postmenopausal women.

Keywords: bone mineral density (BMD); polygenic score (PGS); single nucleotide polymorphism (SNP).

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure A1
Figure A1
Observed versus predicted major osteoporotic fracture (A) and any fracture (B) stratified by polygenic score group, 10 years of follow-up. The dotted line indicates a relative ratio of 1 (reference line); ratio <1 indicates that T-score underestimates fracture risk.
Figure A2
Figure A2
Observed versus predicted major osteoporotic fracture (A) and any fracture (B) probability stratified by race, 10 years of follow-up. The dotted line indicates a relative ratio of 1 (reference line); ratio <1 indicates that T-score underestimates fracture risk.
Figure A3
Figure A3
False-positive rate and false-negative rate for major osteoporotic fracture and any fracture in the analytic sample by polygenic score group, 10 years of follow-up.
Figure A4
Figure A4
False-positive rate and false-negative rate for major osteoporotic fracture and any fracture in the analytic sample by race, 10 years of follow-up.
Figure 1
Figure 1
Observed versus predicted major osteoporotic fracture (A) and any fracture (B) probability stratified by polygenic score group. The dotted line indicates a relative ratio of 1 (reference line); ratio <1 indicates that T-score underestimates fracture risk.
Figure 2
Figure 2
Observed versus predicted major osteoporotic fracture (A) and any fracture (B) probability stratified by race. The dotted line indicates a relative ratio of 1 (reference line), ratio <1 indicates that T-score underestimates fracture risk.
Figure 3
Figure 3
False-positive rate and false-negative rate for major osteoporotic fracture and any fracture in the analytic sample by polygenic score group.
Figure 4
Figure 4
False-positive rate and false-negative rate for major osteoporotic fracture and any fracture in the analytic sample by race.
See this image and copyright information in PMC

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