NDLI: Causal relationship between bone mineral density and intervertebral disc degeneration: a univariate and multivariable mendelian randomization study

Content Provider	Springer Nature : BioMed Central
Author	Li, Luming Li, Dawei Geng, Ziming Huo, Zhenxin Kang, Yuxiang Guo, Xiangxiang Yuan, Bing Xu, Baoshan Wang, Tao
Abstract	Background Although previous studies have suggested a possible association between bone mineral density (BMD) and intervertebral disc degeneration (IDD), the causal relationship between them remains unclear. Evidence from accumulating studies indicates that they might mutually influence one another. However, observational studies may be affected by potential confounders. Meanwhile, Mendelian randomization (MR) study can overcome these confounders to assess causality. Objectives This Mendelian randomization (MR) study aimed to explore the causal effect of bone mineral density (BMD) on intervertebral disc degeneration (IDD). Methods Summary data from genome-wide association studies of bone mineral density (BMD) and IDD (the FinnGen biobank) have been acquired. The inverse variance weighted (IVW) method was utilized as the primary MR analysis approach. Weighted median, MR-Egger regression, weighted mode, and simple mode were used as supplements. The Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) and MR-Egger regression were performed to assess horizontal pleiotropy. Cochran’s Q test evaluated heterogeneity. Leave-one-out sensitivity analysis was further conducted to determine the reliability of the causal relationship. Multivariate MR (MVMR) analyses used multivariable inverse variance-weighted methods to individually and jointly adjust for four potential confounders, body mass index (BMI), Type2 diabetes, hyperthyroidism and smoking. A reverse MR analysis was conducted to assess potential reverse causation. Results In the univariate MR analysis, femoral neck bone mineral density (FNBMD), heel bone mineral density (eBMD), lumbar spine bone mineral density (LSBMD), and total body bone mineral density (TB BMD) had a direct causal effect on intervertebral disc degeneration (IDD) [FNBMD-related analysis: OR(95%CI) = 1.17 (1.04 to 1.31), p = 0.008, eBMD-related analysis: OR(95%CI) = 1.06 (1.01 to 1.12), p = 0.028, LSBMD-related analysis: OR(95%CI) = 1.20 (1.10 to 1.31), p = 3.38E-7,TB BMD-related analysis: OR(95%CI) = 1.20 (1.12 to 1.29), p = 1.0E-8]. In the MVMR analysis, it was revealed that, even after controlling for confounding factors, heel bone mineral density (eBMD), lumbar spine bone mineral density (LSBMD), and total body bone mineral density (TB BMD) still maintained an independent and significant causal association with IDD(Adjusting for heel bone mineral density: beta = 0.073, OR95% CI = 1.08(1.02 to 1.14), P = 0.013; Adjusting for lumbar spine bone mineral density: beta = 0.11, OR(95%CI) = 1.12(1.02 to 1.23), P = 0.03; Adjusting for total body bone mineral density: beta = 0.139, OR95% CI = 1.15(1.06 to 1.24), P = 5.53E − 5). In the reverse analysis, no evidence was found to suggest that IDD has an impact on BMD. Conclusions The findings from our univariate and multivariable Mendelian randomization analysis establish a substantial positive causal association between BMD and IDD, indicating that higher bone mineral density may be a significant risk factor for intervertebral disc degeneration. Notably, no causal effect of IDD on these four measures of bone mineral density was observed. Further research is required to elucidate the underlying mechanisms governing this causal relationship.
Related Links	https://bmcmusculoskeletdisord.biomedcentral.com/counter/pdf/10.1186/s12891-024-07631-7.pdf
Ending Page	10
Page Count	10
Starting Page	1
File Format	HTM / HTML
ISSN	14712474
DOI	10.1186/s12891-024-07631-7
Journal	BMC Musculoskeletal Disorders
Issue Number	1
Volume Number	25
Language	English
Publisher	BioMed Central
Publisher Date	2024-07-05
Access Restriction	Open
Subject Keyword	Orthopedics Rehabilitation Rheumatology Sports Medicine Internal Medicine Epidemiology Osteoporosis Bone mineral density Intervertebral disc degeneration Mendelian randomization (MR) GWAS data
Content Type	Text
Resource Type	Article
Subject	Orthopedics and Sports Medicine Rheumatology
Journal Impact Factor	2.2/2023
5-Year Journal Impact Factor	2.6/2023

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Causal roles of educational duration in bone mineral density and risk factors for osteoporosis: a Mendelian randomization study

Diabetes and osteoporosis: a two-sample mendelian randomization study

Causal relationship between Interleukin-27 expression levels and osteoporosis: a bidirectional mendelian randomization study

Correlation between intervertebral disc degeneration and bone mineral density difference: a retrospective study of postmenopausal women using an eight-level MRI-based disc degeneration grading system

Potential association of rheumatic diseases with bone mineral density and fractures: a bi-directional mendelian randomization study

Bone biochemical markers, bone mineral density, and the risk of osteonecrosis of the femoral head: a Mendelian randomization study

Association of type 2 Diabetes Mellitus and bone mineral density: a two-sample Mendelian randomization study

The association of lipids and novel non-statin lipid-lowering drug target with osteoporosis: evidence from genetic correlations and Mendelian randomization

Gut microbiota and intervertebral disc degeneration: a bidirectional two-sample Mendelian randomization study

Causal relationship between bone mineral density and intervertebral disc degeneration: a univariate and multivariable mendelian randomization study

Similar Documents

Causal roles of educational duration in bone mineral density and risk factors for osteoporosis: a Mendelian randomization study

Diabetes and osteoporosis: a two-sample mendelian randomization study

Causal relationship between Interleukin-27 expression levels and osteoporosis: a bidirectional mendelian randomization study

Correlation between intervertebral disc degeneration and bone mineral density difference: a retrospective study of postmenopausal women using an eight-level MRI-based disc degeneration grading system

Potential association of rheumatic diseases with bone mineral density and fractures: a bi-directional mendelian randomization study

Bone biochemical markers, bone mineral density, and the risk of osteonecrosis of the femoral head: a Mendelian randomization study

Association of type 2 Diabetes Mellitus and bone mineral density: a two-sample Mendelian randomization study

The association of lipids and novel non-statin lipid-lowering drug target with osteoporosis: evidence from genetic correlations and Mendelian randomization

Gut microbiota and intervertebral disc degeneration: a bidirectional two-sample Mendelian randomization study

Causal relationship between bone mineral density and intervertebral disc degeneration: a univariate and multivariable mendelian randomization study