AUTHOR=Jiang Liying , Jiang Ying , Wang Anqi , Wu Cui , Shen Yi 

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

JOURNAL=Frontiers in Endocrinology

VOLUME=13

YEAR=2023

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2022.1021083

DOI=10.3389/fendo.2022.1021083

ISSN=1664-2392

ABSTRACT=<sec><title>Objectives</title><p>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).</p></sec><sec><title>Methods</title><p>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.</p></sec><sec><title>Results</title><p>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, <italic>P</italic>=0.032; for WM: OR=1.257, 95%CI: 1.09-1.45, <italic>P</italic>=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(<italic>P</italic>=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, <italic>P</italic>=0.084 using IVW; OR=1.132, 95%CI: 0.99-1.29, <italic>P</italic>=0.068 using WM; OR=1.274, 95%CI: 0.88-1.85, <italic>P</italic>=0.217 using MR-Egger).</p></sec><sec><title>Conclusions</title><p>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.</p></sec>