Data_Sheet_1_Prediction of medication-related osteonecrosis of the jaws using machine learning methods from estrogen receptor 1 polymorphisms and clinical information.PDF

ObjectiveThe purpose of this study was to evaluate the effect of estrogen receptor 1 (ESR1) polymorphisms on the development of medication-related osteonecrosis of the jaws (MRONJ) in women with osteoporosis.MethodsA total of 125 patients taking bisphosphonates was evaluated the relationship between MRONJ occurrence and single nucleotide polymorphisms (SNPs) of ESR1. Clinical information was collected, including current age, treatment duration, and comorbidity. Univariate and Multivariable regression analyzes were performed to evaluate the independent predictive factors for MRONJ occurrence. Predictive models were constructed using machine learning methods such as Lasso regression, Random forest (RF), and Support vector machine (SVM). The area under the receiver-operating curve (AUROC) was used to evaluate the performance of a binary classifier.ResultTwo SNPs of ESR1 (rs4870056 and rs78177662) were significantly associated with MRONJ development. Patients with variant allele (A) of rs4870056 showed 2.45 times (95% CI, 1.03–5.87) the odds of MRONJ occurrence compared to those with wild-type homozygote (GG) after adjusting covariates. Additionally, carriers with variant allele (T) of rs78177662 had higher odds than those with wild-type homozygote (CC) (adjusted odds ratio (aOR), 2.64, 95% CI, 1.00–6.94). Among demographic variables, age ≥ 72 years (aOR, 3.98, 95% CI, 1.60–9.87) and bisphosphonate exposure ≥48 months (aOR, 3.16, 95% CI, 1.26–7.93) were also significant risk factors for MRONJ occurrence. AUROC values of machine learning methods ranged between 0.756–0.806 in the study.ConclusionOur study showed that the MRONJ occurrence was associated with ESR1 polymorphisms in osteoporotic women.

本研究旨在评估雌激素受体1（ESR1）基因多态性对骨质疏松症女性服用双膦酸盐类药物后发生下颌骨坏死（MRONJ）的影响。研究方法包括对125名服用双膦酸盐的患者的临床信息进行收集，包括当前年龄、治疗时长和合并症。通过单因素和多因素回归分析评估了MRONJ发生的独立预测因素。利用机器学习方法如Lasso回归、随机森林（RF）和支撑向量机（SVM）构建了预测模型。通过受试者工作特征曲线下面积（AUROC）评估二元分类器的性能。研究结果发现，ESR1基因的两个单核苷酸多态性位点（rs4870056和rs78177662）与MRONJ的发生显著相关。携带rs4870056变异等位基因（A）的患者相较于野生型纯合子（GG）发生MRONJ的几率增加了2.45倍（95%置信区间，1.03–5.87）。此外，携带rs78177662变异等位基因（T）的患者发生MRONJ的几率高于野生型纯合子（CC）的患者（调整后的比值比（aOR），2.64，95%置信区间，1.00–6.94）。在人口统计学变量中，年龄≥72岁（aOR，3.98，95%置信区间，1.60–9.87）和双膦酸盐暴露≥48个月（aOR，3.16，95%置信区间，1.26–7.93）也是MRONJ发生的显著风险因素。在本研究中，机器学习方法的AUROC值介于0.756–0.806之间。研究结论表明，骨质疏松症女性MRONJ的发生与ESR1基因多态性相关。