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Updated: Aug 9, 2026

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Machine Learning Approaches for Predicting Bisphosphonate-Related Osteonecrosis in Women with Osteoporosis Using
Jin-Woo Kim1, Jeong Yee2, Sang-Hyeon Oh3
1Department of Oral and Maxillofacial Surgery, School of Medicine, Ewha Womans University, Seoul 07985, Korea.
Objective:
This nested case-control study aimed to investigate the effects of VEGFA polymorphisms on the development of bisphosphonate-related osteonecrosis of the jaw (BRONJ) in women with osteoporosis.
Methods:
Eleven single nucleotide polymorphisms (SNPs) of the VEGFA were assessed in a total of 125 patients. Logistic regression was performed for multivariable analysis. Machine learning algorithms, namely, fivefold cross-validated multivariate logistic regression, elastic net, random forest, and support vector machine, were developed to predict risk factors for BRONJ occurrence. Area under the receiver-operating curve (AUROC) analysis was conducted to assess clinical performance.
Results:
The VEGFA rs881858 was significantly associated with BRONJ development. The odds of BRONJ development were 6.45 times (95% CI, 1.69-24.65) higher among carriers of the wild-type rs881858 allele compared with variant homozygote carriers after adjusting for covariates. Additionally, variant homozygote (GG) carriers of rs10434 had higher odds than those with wild-type allele (OR, 3.16). Age ≥ 65 years (OR, 16.05) and bisphosphonate exposure ≥ 36 months (OR, 3.67) were also significant risk factors for BRONJ occurrence. AUROC values were higher than 0.78 for all machine learning methods employed in this study.
Conclusion:
Our study showed that the BRONJ occurrence was associated with VEGFA polymorphisms in osteoporotic women.
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