AbstractFor a long time, the decline in lung function has been regarded as a potential factor associated with the risk of osteoporosis (OP). Although several observational studies have investigated the relationship between lung function and OP, their conclusions have been inconsistent. Given that Mendelian randomization (MR) studies can help reduce the interference of confounding factors on outcomes, we adopted this approach to explore the causal relationship between lung function and OP at the genetic level.

长期以来，肺功能下降被认为是与骨质疏松症（OP）风险相关的潜在因素。尽管一些观察性研究已经调查了肺功能与OP之间的关系，但他们的结论并不一致。鉴于孟德尔随机化（MR）研究可以帮助减少混杂因素对结果的干扰，我们采用这种方法在遗传水平上探索肺功能与OP之间的因果关系。

To investigate the potential causality between lung function (FVC, FEV1, FEV1/FVC, PEF) and OP, we conducted a MR analysis employing three approaches: inverse variance weighted (IVW), MR-Egger, and weighted median. We used Cochran’s Q test to detect potential heterogeneity, MR-Egger regression to evaluate directional pleiotropy, and the MR-PRESSO method to evaluate horizontal pleiotropy.

为了研究肺功能（FVC，FEV1，FEV1/FVC，PEF）与OP之间的潜在因果关系，我们采用三种方法进行了MR分析：逆方差加权（IVW），MR-Egger和加权中位数。我们使用Cochran的Q检验来检测潜在的异质性，使用MR-Egger回归来评估方向多效性，使用MR-PRESSO方法来评估水平多效性。

In addition, we used MR-PRESSO and MR radial methods to exclude SNPs exhibiting pleiotropic outliers. Upon identification of potential outliers, we removed them and subsequently ran MR analysis again to assess the reliability of our findings. The MR analysis suggested that there was no causal effect of lung function (FVC, PEF, FEV1/FVC, FEV1) on OP, which is consistent with the.

此外，我们使用MR-PRESSO和MR-radial方法排除了表现出多效性异常值的SNP。在确定潜在异常值后，我们删除了它们，随后再次进行MR分析以评估我们发现的可靠性。MR分析表明，肺功能（FVC，PEF，FEV1/FVC，FEV1）对OP没有因果关系，这与。

results after excluding potential outliers using MR-PRESSO and MR radial. methods. Sensitivity analysis confirmed the reliability and consistency of these. results. The study concluded that there is no causal link between lung function and OP. The association found in observational studies might be attributable to shared risk factors..

使用MR-PRESSO和MR-radial排除潜在异常值后的结果。方法。敏感性分析证实了这些的可靠性和一致性。结果。该研究得出结论，肺功能与OP之间没有因果关系。观察性研究中发现的关联可能归因于共同的危险因素。。

IntroductionOsteoporosis (OP) is a metabolic bone disorder disease characterized by diminished bone density, compromised bone integrity, and deterioration of bone microarchitecture, culminating in heightened susceptibility to fragility fractures1. OP is linked to elevated medical expenses, physical incapacitation, diminished quality of life, and heightened mortality rates2.

引言骨质疏松症（OP）是一种代谢性骨病，其特征在于骨密度降低，骨完整性受损和骨微结构恶化，最终导致对脆性骨折的易感性增加1。OP与医疗费用增加，身体残疾，生活质量下降和死亡率升高有关2。

In the United States, an estimated 10.2 million older adults were diagnosed with OP in 2010, while approximately 43.4 million older adults exhibited low bone density3. With the acceleration of global aging, OP has emerged as a significant public health concern in contemporary society4,5. Hence, it is imperative to ascertain the risk factors associated with OP to facilitate the prompt implementation of interventions and mitigate the occurrence of adverse clinical events related to OP, thereby enhancing the prognosis for the elderly population.Lung function tests play a crucial role in assessing respiratory health, particularly in detecting conditions like asthma and early-onset airway diseases6.

在美国，2010年估计有1020万老年人被诊断出患有OP，而大约4340万老年人表现出低骨密度3。随着全球老龄化的加速，OP已成为当代社会重要的公共卫生问题4,5。因此，必须确定与OP相关的风险因素，以促进干预措施的迅速实施，并减轻与OP相关的不良临床事件的发生，从而改善老年人群的预后。肺功能测试在评估呼吸系统健康方面起着至关重要的作用，特别是在检测哮喘和早发性气道疾病等疾病方面6。

Key metrics include the forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), peak expiratory flow (PEF), and the FEV1/FVC ratio7,8. These indicators are essential for diagnosing conditions such as chronic obstructive pulmonary disease (COPD), as well as assessing the extent of airway constriction and lung impairment9.

关键指标包括1秒用力呼气量（FEV1），用力肺活量（FVC），呼气峰流量（PEF）和FEV1/FVC比率7,8。这些指标对于诊断慢性阻塞性肺病（COPD）等疾病以及评估气道收缩和肺损伤的程度至关重要9。

Multiple prior studies have investigated the correlation between lung function and bone metabolism; however, the results have shown inconsistency. S Lekamwasam et al. have reported a significant decrease in bone mineral density (BMD) at the total hip and femoral neck with the deterioration of pulmonary function10.

多项先前的研究已经调查了肺功能与骨代谢之间的相关性；然而，结果显示不一致。S Lekamwasam等人报道，随着肺功能的恶化，全髋关节和股骨颈的骨密度（BMD）显着降低10。

A study conducted in China reveals a significant association betwee.

在中国进行的一项研究表明，两者之间存在显着关联。

Data availability

数据可用性

The GWAS summary statistics used in this MR study are available in Open GWAS. The R scripts applied in the two-sample MR analysis and shell codes used in genetic correlation analysis are available from the author (Rui Jiang, E-mial: jrui388@gmail.com) upon request. FVC: (https://gwas.mrcieu.ac.uk/datasets/ebi-a-GCST007429/), PEF: (https://gwas.mrcieu.ac.uk/datasets/ebi-a-GCST007430/), FEV1/FVC: (https://gwas.mrcieu.ac.uk/datasets/ebi-a-GCST007431/), FEV1: (https://gwas.mrcieu.ac.uk/datasets/ebi-a-GCST007431/), Osteoporosis: (https://gwas.mrcieu.ac.uk/datasets/finn-b-M13_OSTEOPOROSIS/)..

本MR研究中使用的GWAS摘要统计数据可在Open GWAS中获得。作者（Rui Jiang，E-emial：jrui388@gmail.com)根据要求。FVC：(https://gwas.mrcieu.ac.uk/datasets/ebi-a-GCST007429/)，产品环境足迹：(https://gwas.mrcieu.ac.uk/datasets/ebi-a-GCST007430/)，FEV1/FVC：(https://gwas.mrcieu.ac.uk/datasets/ebi-a-GCST007431/)，FEV1：(https://gwas.mrcieu.ac.uk/datasets/ebi-a-GCST007431/)，骨质疏松症：(https://gwas.mrcieu.ac.uk/datasets/finn-b-M13_OSTEOPOROSIS/)。。

AbbreviationsOP:

缩写OP：

osteoporosis

骨质疏松症

FEV1:

二月一日：

forced expiratory volume in 1 s

1秒用力呼气量

FVC:

FVC：

forced vital capacity

用力肺活量

PEF:

产品环境足迹：

peak expiratory flow

COPD:

慢性阻塞性肺疾病：

chronic obstructive pulmonary disease

慢性阻塞性肺疾病

BMD:

骨密度：

bone mineral density

骨矿物质密度

MR:

先生：

Mendelian randomization

IVs:

IV：

instrumental variables

工具变量

CI:

CI公司：

confidence interval

置信区间

GWAS:

GWAS：

genome-wide association studies

全基因组关联研究

IVW:

IVW：

inverse variance weighted

逆方差加权

SNPs:

单核苷酸多态性：

single nucleotide polymorphisms

单核苷酸多态性

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Download referencesAcknowledgementsWe sincerely thank all the participants for their valuable contributions to this study, which utilized publicly available data from prior research studies.FundingThis study was supported by the Natural Science Foundation of Hubei Province (2024AFB976).Author informationAuthor notesRui Jiang, Zhongshan Li and Caiguo Zhang contributed equally to this work.Authors and AffiliationsGraduate school, Hubei University of Traditional Chinese Medicine, 16 Huangjiahu West Road, Wuhan, 430065, ChinaRui Jiang, Zhongshan Li, Caiguo Zhang, Shuangqiang Tu, Zixuan Huang & Zheng ZhangDepartment of Orthopedics, Huanggang Hospital of Traditional Chinese Medicine affiliated with Hubei University of Chinese Medicine, 19 Dongmen Road, Huanggang, 438000, ChinaRui Jiang, Zhongshan Li, Caiguo Zhang, Gengchao Zhang, Qi Qu, Shuangqiang Tu, Zhiyu Wang & Zheng ZhangDepartment of Rehabilitation, Huanggang Central Hospital, 126 Qian Avenue, Huanggang, 438000, ChinaFeng LuoMedical college, Hubei Minzu University, 39 Xueyuan Road, Enshi, 445000, ChinaGengchao Zhang, Qi Qu & Zhiyu WangAuthorsRui JiangView author publicationsYou can also search for this author in.

下载参考文献致谢我们衷心感谢所有参与者对本研究的宝贵贡献，该研究利用了先前研究的公开数据。资助该研究得到了湖北省自然科学基金（2024AFB976）的支持。作者信息作者注意到江瑞、李中山和张蔡国对这项工作做出了同样的贡献。作者和附属机构湖北中医药大学研究生院，武汉黄家湖西路16号，430065，中国江瑞、李中山、张蔡国、涂双强、黄紫轩和张郑湖北中医药大学附属黄冈中医院骨科，黄冈东门路19号，438000，中国江瑞、李中山、张蔡国、张耿超、齐曲、涂双强、王志宇和张郑黄冈市中心医院康复科，黄冈前大道126号，438000，湖北民族大学华丰医学院，恩施学院路39号，邮编445000，中国张庚超，Qi Qu＆Zhiyu WangAuthorsRui JiangView作者出版物您也可以在中搜索这位作者。

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PubMed Google ScholarContributionsR.J, ZS.L, and CG.Z wrote the main manuscript text. L.F, Q.Q, and SQ.T. reviewed and edited the manuscript. ZYW and ZZ proposed a concept of the manuscript. All authors reviewed the manuscript.Corresponding authorsCorrespondence to

PubMed谷歌学术贡献。J、 ZS公司。五十、 和CG。Z写了主要的手稿文本。五十、 。ZYW和ZZ提出了手稿的概念。所有作者都审阅了手稿。通讯作者通讯

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Competing interests

相互竞争的利益

The authors declare no competing interests.

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Ethics approval and consent to participate

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The data utilized in this work is derived from public databases, and its information is publicly accessible and permitted for unrestricted reuse under an open license.

这项工作中使用的数据来自公共数据库，其信息可公开访问，并允许在开放许可下不受限制地重复使用。

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提交声明和验证

We confirm that the manuscript contains novel research findings that have not been previously published and are not presently under consideration elsewhere. All authors have thoroughly reviewed and agreed to submit this manuscript.

我们确认，手稿包含以前没有发表过的新颖研究结果，目前也没有在其他地方考虑。所有作者都已经彻底审查并同意提交这份手稿。

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道德声明

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数据来自可公开访问的数据库，不涉及人类受试者；因此，道德参数不适用。

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Reprints and permissionsAbout this articleCite this articleJiang, R., Li, Z., Zhang, C. et al. No genetic causal relationship between lung function and osteoporosis ― evidence from a mendelian randomization study.

转载和许可本文引用本文Jiang，R.，Li，Z.，Zhang，C。等人。肺功能与骨质疏松症之间没有遗传因果关系-来自孟德尔随机研究的证据。

Sci Rep 14, 24334 (2024). https://doi.org/10.1038/s41598-024-76116-3Download citationReceived: 25 May 2024Accepted: 10 October 2024Published: 17 October 2024DOI: https://doi.org/10.1038/s41598-024-76116-3Share this articleAnyone you share the following link with will be able to read this content:Get shareable linkSorry, a shareable link is not currently available for this article.Copy to clipboard.

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KeywordsLung functionOsteoporosisBone mineral densityMendelian randomization

关键词骨功能骨质疏松症骨矿物质密度私人随机化