{"title":"Potential causal effect of SLE on osteoporosis, and the mediation effect: a Mendelian randomisation study.","authors":"Zhaoqing Wang, Jiaxuan Yang, Qingya Shi, Bojie Liu, Ying Liang, Yangzhong Zhou, Guanqiao Li","doi":"10.1136/lupus-2025-001735","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>This study uses Mendelian randomisation (MR) to investigate the causal link between SLE and osteoporosis across different ethnic groups.</p><p><strong>Methods: </strong>Genetic variants associated with SLE were identified from publicly available genome-wide association studies in European and East Asian populations. Two-sample MR (TSMR) analysis and meta-analysis with inverse variance weighting (IVW) assessed their effects on bone mineral density (BMD) and fracture risk. Multivariable MR (MVMR) analysis in East Asians adjusted for potential mediators, and two-step mediation analysis evaluated mediation effects of independent covariates.</p><p><strong>Results: </strong>A meta-analysis of IVW results from TSMR in East Asian populations revealed a significant positive genetic association of SLE with osteoporosis (OR=1.023, CI 1.007 to 1.040, p<0.01). A similar, although weaker, association was observed in the European population (OR=1.001, CI 1.000 to 1.001, p<0.01). Furthermore, SLE was identified as a risk factor for reduced BMD in both East Asian (β=-0.0690, p<0.05) and European (β=-0.0109, p<0.05) populations, and for fracture risk in European (OR=1.002, p<0.05) populations, while no significant association was observed in the East Asian population (OR=1.010, p=0.705). MVMR analysis of East Asian data assessed mediation effects and found that the SLE-osteoporosis association was nullified after adjusting for cardiovascular disease and health status. Mediation analysis identified low-density lipoprotein cholesterol (LDL-C) and anti-inflammatory medication use as independent mediators, with mediation effects of 0.1170 and 0.0510, respectively. No significant heterogeneity or pleiotropy was detected.</p><p><strong>Conclusions: </strong>SLE appears to be a causal risk factor for osteoporosis. LDL-C and anti-inflammatory medication use mediate this relationship, suggesting the importance of managing these factors in patients with SLE to reduce osteoporosis risk.</p>","PeriodicalId":18126,"journal":{"name":"Lupus Science & Medicine","volume":"12 2","pages":""},"PeriodicalIF":3.5000,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12481273/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Lupus Science & Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1136/lupus-2025-001735","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"RHEUMATOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Objective: This study uses Mendelian randomisation (MR) to investigate the causal link between SLE and osteoporosis across different ethnic groups.
Methods: Genetic variants associated with SLE were identified from publicly available genome-wide association studies in European and East Asian populations. Two-sample MR (TSMR) analysis and meta-analysis with inverse variance weighting (IVW) assessed their effects on bone mineral density (BMD) and fracture risk. Multivariable MR (MVMR) analysis in East Asians adjusted for potential mediators, and two-step mediation analysis evaluated mediation effects of independent covariates.
Results: A meta-analysis of IVW results from TSMR in East Asian populations revealed a significant positive genetic association of SLE with osteoporosis (OR=1.023, CI 1.007 to 1.040, p<0.01). A similar, although weaker, association was observed in the European population (OR=1.001, CI 1.000 to 1.001, p<0.01). Furthermore, SLE was identified as a risk factor for reduced BMD in both East Asian (β=-0.0690, p<0.05) and European (β=-0.0109, p<0.05) populations, and for fracture risk in European (OR=1.002, p<0.05) populations, while no significant association was observed in the East Asian population (OR=1.010, p=0.705). MVMR analysis of East Asian data assessed mediation effects and found that the SLE-osteoporosis association was nullified after adjusting for cardiovascular disease and health status. Mediation analysis identified low-density lipoprotein cholesterol (LDL-C) and anti-inflammatory medication use as independent mediators, with mediation effects of 0.1170 and 0.0510, respectively. No significant heterogeneity or pleiotropy was detected.
Conclusions: SLE appears to be a causal risk factor for osteoporosis. LDL-C and anti-inflammatory medication use mediate this relationship, suggesting the importance of managing these factors in patients with SLE to reduce osteoporosis risk.
期刊介绍:
Lupus Science & Medicine is a global, peer reviewed, open access online journal that provides a central point for publication of basic, clinical, translational, and epidemiological studies of all aspects of lupus and related diseases. It is the first lupus-specific open access journal in the world and was developed in response to the need for a barrier-free forum for publication of groundbreaking studies in lupus. The journal publishes research on lupus from fields including, but not limited to: rheumatology, dermatology, nephrology, immunology, pediatrics, cardiology, hepatology, pulmonology, obstetrics and gynecology, and psychiatry.