The causal association between bone mineral density and risk of osteoarthritis: A Mendelian randomization study

Liying Jiang; Ying Jiang; Anqi Wang; Cui Wu; Yi Shen

doi:10.3389/fendo.2022.1021083

The causal association between bone mineral density and risk of osteoarthritis: A Mendelian randomization study

Front Endocrinol (Lausanne). 2023 Jan 11:13:1021083. doi: 10.3389/fendo.2022.1021083. eCollection 2022.

Authors

Liying Jiang^{1

2}, Ying Jiang³, Anqi Wang⁴, Cui Wu⁵, Yi Shen⁶

Affiliations

¹ Department of Prevention Medicine, College of Public health, Shanghai University of Medicine & Health Sciences, Shanghai, China.
² Jiading Central Hospital, Shanghai University of Medicine & Health Sciences, Shanghai, China.
³ Department of Health, Center for Disease Control and Prevention in Suqian, Suqian, Jiangsu Province, China.
⁴ Department of Nursing, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
⁵ Department of Non-communicable Disease, Baoshan District Center for Disease Control and Prevention in Shanghai, Shanghai, China.
⁶ Department of Epidemiology, School of Public Health, Nantong University, Nantong, Jiangsu Province, China.

Abstract

Objectives: The causal direction and magnitude of the association between total body bone mineral density (TB-BMD) and osteoarthritis (OA) risk is uncertain owing to the susceptibility of observational studies to confounding and reverse causation. The study aimed to explore the relationships between TB-BMD concentration and OA using Mendelian randomization (MR).

Methods: In this study, we used two-sample MR to obtain unconfounded estimates of the effect of TB-BMD on hip and knee OA. Single nucleotide polymorphisms (SNPs) strongly associated with TB-BMD in a large genome-wide association study (GWAS) were identified and selected as instrumental variables (IVs). In addition to the main analysis using inverse-variance weighted (IVW) method, we applied 2 additional methods to control for pleiotropy(MR-Egger regression, weighted median estimator) and compared the respective MR estimates.

Results: MR analyses suggested that genetically predicted higher TB-BMD is associated with risks of hip OA (For IVW: OR=1.199, 95%CI: 1.02-1.42, P=0.032; for WM: OR=1.257, 95%CI: 1.09-1.45, P=0.002). There was no evidence that the observed causal effect between TB-BMD and the risk of hip OA was affected by genetic pleiotropy(P=0.618). Additionally, our study didn't support causal effects of a genetically increased TB-BMD risk on knee OA risk(OR=1.121, 95%CI: 0.99-1.28, P=0.084 using IVW; OR=1.132, 95%CI: 0.99-1.29, P=0.068 using WM; OR=1.274, 95%CI: 0.88-1.85, P=0.217 using MR-Egger).

Conclusions: Our findings support a causal effect that a genetic predisposition to systematically higher TB-BMD was associated with the risk of OA. And, TB-BMD likely exerts an effect on the risk of hip OA not knee OA.

Keywords: Mendelian randomization; bone mineral density; genome-wide association studies; osteoarthritis; single nucleotide polymorphisms.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Bone Density / genetics
Genome-Wide Association Study
Humans
Mendelian Randomization Analysis
Osteoarthritis, Hip* / genetics
Osteoarthritis, Knee* / epidemiology
Osteoarthritis, Knee* / genetics

Grants and funding

This study was supported by teacher professional progress project in Shanghai, and Local High-level University (cultivation) project in Shanghai (E1-2602-21-201006-6), and supported by the Shanghai Municipal Health Commission (201840297), and supported by The Training Planned Fund of Academic Leaders from Shanghai Pudong New Area Health System (PWR 12018-09).