时间标签：数据日期 2026-10-31 · 生成时间 2026-11-01 05:30（Asia/Shanghai）｜ 检索窗口 PubMed edat 2026/10/28–2026/10/31 ｜ 情报发生日期 2026-10-31
研究问题
The prevalence of CHIP has been estimated to be about 10% in individuals over the age of 70 years; however, studies using error-corrected and deep read sequencing to identify mutations at a lower VAF have identified CHIP at much higher frequencies, at rates of up to 95% of healthy individuals after the age of 50.；[, ] However, there remains limited data that confirm the relationship between CHIP and osteoporosis, particularly in human cohorts, and little is known about the mechanism driving CHIP-related changes in bone density and whether there are sex differences.
方法
We investigated cohorts that were part of the NHLBI’s TOPMed program and underwent whole-genome sequencing (WGS).；[] The TOPMed dataset used in the analyses consisted of over 158,000 individuals across over 80 studies.；[] The current report is based on WGS performed on 97,691 samples obtained from 51 separate cohorts as a part of TOPMed Freeze 6, from which somatic mutations consistent with CHIP were identified using GATK Mutect2 if the VAF was greater than 2%.；[] This dataset of CHIP calls was culled from cohort participants aged 60 years and older who also had measures of BMD (n=3,368).
核心结论
Femoral neck BMD (FNBMD) was comparable across groups, but the lumbar spine BMD (LSBMD) was slightly higher in persons with two or more CHIP mutations in multiple genes.；The presence of any CHIP mutations was not associated with either FNBMD or LSBMD ().；CHIP status was further classified into categories: no mutations, one CHIP mutation, two or more CHIP mutations in a single gene, or two or more CHIP mutations in different genes. ‖ 结论：Our findings of greater BMD in persons harboring CHIP mutations in more than one CHIP gene are in line with experiments in mouse models demonstrating that introduction of Dnmt3a and Tet2 mutations independently cause increased bone density.
局限
Third, in the UK Biobank samples, BMD was estimated from quantitative heel ultrasound measures, which correlate only modestly with DXA-derived BMD of the hip and spine used in our study (r=0.31 to 0.37)[] Fourth, we cannot rule out the possibility that the higher spine density observed in persons with multiple CHIP mutations could be driven by age related changes in vascular calcification or degenerative spine changes related to CHIP.；We do not feel this latter possibility is likely given a parallel finding we observed in the peripheral skeleton using high resolution peripheral quantitative computed tomography (HR-pQCT).[] In that preliminary study of CHIP mutations and HR-pQCT measures, the
对本项目的价值
★☆☆☆☆ 衰弱/肌少症是少有的已有监管认可终点的老年综合征，是临床转化的最短路径。队列：Framingham。
全文来源
PMC JATS 全文（正文 17,990 字符，已过标题/DOI 逐字归属校验）
原文题录
- 英文标题：Clonal Hematopoiesis of Indeterminate Potential and Bone Mineral Density in Cohorts from Trans-Omics for Precision Medicine.
- 期刊与标识：J Bone Miner Res · PMID 42949023 · DOI 10.1093/jbmr/zjag148
A 级证据分级：A 级（同行评议人体研究）
本文属人体研究证据，但需注意：观察性或小样本干预的结论不等于已证实临床获益；效应量与长期安全性仍需更大规模、更长随访的试验验证。
关于本文的文献来源：本站依据 IMA 知识库「五刊监控·深度文献卡片」撰写，依据已获取的期刊全文（方法、样本量与结论已回到原文核对）；未能获取全文的同批条目另行标注「摘要级」，全程未做任何数值推算补全。