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Abstract：
BACKGROUND: Osteoporotic vertebral compression fractures (OVCF) in the elderly increase refracture risk post-surgery, leading to higher mortality rates. Genome-wide association studies (GWAS) have identified susceptibility genes for osteoporosis, but the phenotypic variance explained by these genes has been limited, indicating the need to explore additional causal factors. Epigenetic modifications, such as DNA methylation, may influence osteoporosis and refracture risk. However, prospective cohorts for assessing epigenetic alterations in Chinese elderly patients are lacking. Here, we propose to conduct a prospective cohort study to investigate the causal network of DNA polymorphisms, DNA methylation, and environmental factors on the development of osteoporosis and the risk of refracture.
METHODS: We will collect vertebral and peripheral blood from 500 elderly OVCF patients undergoing surgery, extract DNA, and generate whole genome genotype data and DNA methylation data. Observation indicators will be collected and combined with one-year follow-up data. A healthy control group will be selected from a natural population cohort. Epigenome-wide association studies (EWAS) of osteoporosis and bone mineral density will be conducted. Differential methylation analysis will compare candidate gene methylation patterns in patients with and without refracture. Multi-omics prediction models using genetic variants and DNA methylation sites will be built to predict OVCF risk.
CONCLUSIONS: This study will be the first large-scale population-based study of osteoporosis and bone mineral density phenotypes based on genome-wide data, multi-time point methylation data, and phenotype data. By analyzing methylation changes related to osteoporosis and bone mineral density in OVCF patients, the study will explore the feasibility of DNA methylation in evaluating postoperative osteoporosis intervention effects. The findings may identify new molecular markers for effective anti-osteoporosis treatment and inform individualized prevention and treatment strategies.
BACKGROUND: chictr.org.cn ChiCTR2200065316, 02/11/2022.
METHODS: We will collect vertebral and peripheral blood from 500 elderly OVCF patients undergoing surgery, extract DNA, and generate whole genome genotype data and DNA methylation data. Observation indicators will be collected and combined with one-year follow-up data. A healthy control group will be selected from a natural population cohort. Epigenome-wide association studies (EWAS) of osteoporosis and bone mineral density will be conducted. Differential methylation analysis will compare candidate gene methylation patterns in patients with and without refracture. Multi-omics prediction models using genetic variants and DNA methylation sites will be built to predict OVCF risk.
CONCLUSIONS: This study will be the first large-scale population-based study of osteoporosis and bone mineral density phenotypes based on genome-wide data, multi-time point methylation data, and phenotype data. By analyzing methylation changes related to osteoporosis and bone mineral density in OVCF patients, the study will explore the feasibility of DNA methylation in evaluating postoperative osteoporosis intervention effects. The findings may identify new molecular markers for effective anti-osteoporosis treatment and inform individualized prevention and treatment strategies.
BACKGROUND: chictr.org.cn ChiCTR2200065316, 02/11/2022.
摘要：
背景：老年人骨质疏松性椎体压缩性骨折（OVCF）增加术后再骨折风险，导致更高的死亡率。全基因组关联研究（GWAS）已经确定了骨质疏松症的易感基因，但是这些基因解释的表型变异是有限的，这表明需要探索其他因果因素。表观遗传修饰,比如DNA甲基化，可能影响骨质疏松症和再骨折的风险。然而,缺乏评估中国老年患者表观遗传改变的前瞻性队列。这里,我们建议进行前瞻性队列研究来调查DNA多态性的因果网络，DNA甲基化，和环境因素对骨质疏松症的发展和再骨折的风险。
方法：我们将收集500名接受手术的老年OVCF患者的椎体和外周血，提取DNA,并生成全基因组基因型数据和DNA甲基化数据。将收集观察指标并与一年的随访数据相结合。健康对照组将从自然群体队列中选择。将进行骨质疏松症和骨矿物质密度的全基因组关联研究（EWAS）。差异甲基化分析将比较有和没有骨折的患者的候选基因甲基化模式。将建立使用遗传变异和DNA甲基化位点的多组学预测模型来预测OVCF风险。
结论：这项研究将是第一个基于全基因组数据的骨质疏松症和骨密度表型的大规模人群研究，多时间点甲基化数据，和表型数据。通过分析OVCF患者骨质疏松和骨密度相关的甲基化变化,本研究将探讨DNA甲基化评估术后骨质疏松干预效果的可行性。这些发现可能为有效的抗骨质疏松治疗确定新的分子标志物，并为个体化的预防和治疗策略提供信息。
背景：chictr.org.cnChiCTR2200065316,02/11/2022。
方法：我们将收集500名接受手术的老年OVCF患者的椎体和外周血，提取DNA,并生成全基因组基因型数据和DNA甲基化数据。将收集观察指标并与一年的随访数据相结合。健康对照组将从自然群体队列中选择。将进行骨质疏松症和骨矿物质密度的全基因组关联研究（EWAS）。差异甲基化分析将比较有和没有骨折的患者的候选基因甲基化模式。将建立使用遗传变异和DNA甲基化位点的多组学预测模型来预测OVCF风险。
结论：这项研究将是第一个基于全基因组数据的骨质疏松症和骨密度表型的大规模人群研究，多时间点甲基化数据，和表型数据。通过分析OVCF患者骨质疏松和骨密度相关的甲基化变化,本研究将探讨DNA甲基化评估术后骨质疏松干预效果的可行性。这些发现可能为有效的抗骨质疏松治疗确定新的分子标志物，并为个体化的预防和治疗策略提供信息。
背景：chictr.org.cnChiCTR2200065316,02/11/2022。
