Generic placeholder image

Current Rheumatology Reviews

Editor-in-Chief

ISSN (Print): 1573-3971
ISSN (Online): 1875-6360

Research Article

Analysis of the Relationship between Rheumatoid Arthritis and Osteoporosis Based on Mendelian Randomization

Author(s): Song Feichao, Chen Rongrong, Shichang Ji, Bingjie Liu and Zhang Junfeng*

Volume 20, Issue 3, 2024

Published on: 01 November, 2023

Page: [284 - 295] Pages: 12

DOI: 10.2174/0115733971261225231021173529

Price: $65

Abstract

Background: As the global population ages, the World Health Organization has found a yearly increase in the incidence of rheumatoid arthritis and osteoporosis. This trend poses a challenge to public health and healthcare and calls for the implementation of more preventive and treatment measures to address these health issues.

Objective: This study aims to investigate the causal relationship between rheumatoid arthritis (RA) and osteoporosis (OP) using the Mendelian randomization (MR) method.

Methods: OP diagnosis was based on the gold standard of bone mineral density (BMD). Single nucleotide polymorphisms (SNPs) were identified from the genome-wide association research database formed by RA and BMD, with a parameter setting of P < 5×10-8, chain imbalance r2<0.01, and kb = 10,000. Five complementary MR methods, including inverse variance weighted (IVW), MR-Egger regression, weighted median, simple mode estimation based on mode, and weighted estimation based on mode, were used to evaluate the causal relationship between RA and OP/BMD using odds ratio (OR) values and 95% confidence intervals (CI). Sensitivity analyses were performed using heterogeneity tests, horizontal pleiotropy, and individual rejection tests.

Results: A total of 78 instrumental variables were identified that were closely related to both RA and BMD in mixed populations, while 14 instrumental variables were identified in the European population and 38 instrumental variables were identified in the Asian population. Using IVW as the main analysis method, the MR analysis results of RA and BMD showed the following: mixed population OR = 0.96, 95%CI: 0.93-1.00; European population OR = 0.55, 95%CI: 0.27-1.12; and Asian population OR = 0.95, 95%CI: 0.90-1.01. Sensitivity analyses showed that the MR results were robust.

Conclusion: The study found insufficient evidence of a causal relationship between RA and OP/BMD, suggesting that RA may not have a direct effect on OP/BMD.

Graphical Abstract

[1]
Mochizuki T, Ikari K, Yano K, Okazaki K. Five-year incidence of common comorbidities, such as hypertension, dyslipidemia, diabetes mellitus, cardiovascular disease, cerebrovascular disease and cancer, in older Japanese patients with rheumatoid arthritis. Geriatr Gerontol Int 2019; 19(7): 577-81.
[http://dx.doi.org/10.1111/ggi.13664] [PMID: 30950139]
[2]
Sparks JA. Rheumatoid arthritis. Ann Intern Med 2019; 170(1): ITC1-ITC16.
[http://dx.doi.org/10.7326/AITC201901010] [PMID: 30596879]
[3]
Rheumatoid arthritis. Nat Rev Dis Primers 2018; 4(1): 18002.
[http://dx.doi.org/10.1038/nrdp.2018.2] [PMID: 29417950]
[4]
Laufer VA, Tiwari HK, Reynolds RJ, et al. Genetic influences on susceptibility to rheumatoid arthritis in African-Americans. Hum Mol Genet 2019; 28(5): 858-74.
[http://dx.doi.org/10.1093/hmg/ddy395] [PMID: 30423114]
[5]
Wheeler AM, Baker JF, Poole JA, et al. Genetic, social, and environmental risk factors in rheumatoid arthritis-associated interstitial lung disease. Semin Arthritis Rheum 2022; 57: 152098.
[http://dx.doi.org/10.1016/j.semarthrit.2022.152098] [PMID: 36155967]
[6]
Xu Y, Wu Q. Prevalence trend and disparities in rheumatoid arthritis among US adults, 2005-2018. J Clin Med 2021; 10(15): 3289.
[http://dx.doi.org/10.3390/jcm10153289] [PMID: 34362073]
[7]
Jin S, Li M, Fang Y, et al. Chinese Registry of rheumatoid arthritis (CREDIT): II. Prevalence and risk factors of major comorbidities in Chinese patients with rheumatoid arthritis. Arthritis Res Ther 2017; 19(1): 251.
[http://dx.doi.org/10.1186/s13075-017-1457-z] [PMID: 29141688]
[8]
Malhotra H, Garg V, Singh G. Biomarker approach towards rheumatoid arthritis treatment. Curr Rheumatol Rev 2021; 17(2): 162-75.
[http://dx.doi.org/10.2174/1573397116666201216164013] [PMID: 33327920]
[9]
Gibofsky A. Epidemiology, pathophysiology, and diagnosis of rheumatoid arthritis: A Synopsis. Am J Manag Care 2014; 20(7): S128-35.
[PMID: 25180621]
[10]
Semb AG, Ikdahl E, Wibetoe G, Crowson C, Rollefstad S. Atherosclerotic cardiovascular disease prevention in rheumatoid arthritis. Nat Rev Rheumatol 2020; 16(7): 361-79.
[http://dx.doi.org/10.1038/s41584-020-0428-y] [PMID: 32494054]
[11]
Mohammad A, Lohan D, Bergin D, et al. The prevalence of vertebral fracture on vertebral fracture assessment imaging in a large cohort of patients with rheumatoid arthritis. Rheumatology 2014; 53(5): 821-7.
[http://dx.doi.org/10.1093/rheumatology/ket353] [PMID: 24249032]
[12]
Gómez O, Talero AP, Zanchetta MB, et al. Diagnostic, treatment, and follow-up of osteoporosis—position statement of the Latin American Federation of Endocrinology. Arch Osteoporos 2021; 16(1): 114.
[http://dx.doi.org/10.1007/s11657-021-00974-x] [PMID: 34302550]
[13]
Roh YH, Lee ES, Ahn J, et al. Factors affecting willingness to get assessed and treated for osteoporosis. Osteoporos Int 2019; 30(7): 1395-401.
[http://dx.doi.org/10.1007/s00198-019-04952-5] [PMID: 30944954]
[14]
Wysham KD, Baker JF, Shoback DM. Osteoporosis and fractures in rheumatoid arthritis. Curr Opin Rheumatol 2021; 33(3): 270-6.
[http://dx.doi.org/10.1097/BOR.0000000000000789] [PMID: 33651725]
[15]
Hariton E, Locascio JJ. Randomised controlled trials - the gold standard for effectiveness research. BJOG 2018; 125(13): 1716.
[http://dx.doi.org/10.1111/1471-0528.15199] [PMID: 29916205]
[16]
Birney E. Mendelian randomization. Cold Spring Harb Perspect Med 2022; 12(4): a040980.
[PMID: 34872952]
[17]
Ference BA, Holmes MV, Smith GD. Using mendelian randomization to improve the design of randomized trials. Cold Spring Harb Perspect Med 2021; 11(7): a040980.
[http://dx.doi.org/10.1101/cshperspect.a040980] [PMID: 33431510]
[18]
Boef AGC, Dekkers OM, le Cessie S. Mendelian randomization studies: A review of the approaches used and the quality of reporting. Int J Epidemiol 2015; 44(2): 496-511.
[http://dx.doi.org/10.1093/ije/dyv071] [PMID: 25953784]
[19]
Zheng J, Baird D, Borges MC, et al. Recent developments in mendelian randomization studies. Curr Epidemiol Rep 2017; 4(4): 330-45.
[http://dx.doi.org/10.1007/s40471-017-0128-6] [PMID: 29226067]
[20]
Gupta V, Walia GK, Sachdeva MP. ‘Mendelian randomization’: An approach for exploring causal relations in epidemiology. Public Health 2017; 145: 113-9.
[http://dx.doi.org/10.1016/j.puhe.2016.12.033] [PMID: 28359378]
[21]
Xia J, Xie SY, Liu KQ, et al. Systemic evaluation of the relationship between psoriasis, psoriatic arthritis and osteoporosis: Observational and Mendelian randomisation study. Ann Rheum Dis 2020; 79(11): 1460-7.
[http://dx.doi.org/10.1136/annrheumdis-2020-217892] [PMID: 32737104]
[22]
Bowden J, Del Greco M F, Minelli C, Davey Smith G, Sheehan N, Thompson J. A framework for the investigation of pleiotropy in two-sample summary data Mendelian randomization. Stat Med 2017; 36(11): 1783-802.
[http://dx.doi.org/10.1002/sim.7221] [PMID: 28114746]
[23]
Gronau QF, Wagenmakers EJ. Limitations of bayesian leave-one-out cross-validation for model selection. Comput Brain Behav 2019; 2(1): 1-11.
[http://dx.doi.org/10.1007/s42113-018-0011-7] [PMID: 30906917]
[24]
Burgess S, Thompson SG. Interpreting findings from mendelian randomization using the MR-egger method. Eur J Epidemiol 2017; 32(5): 377-89.
[http://dx.doi.org/10.1007/s10654-017-0255-x] [PMID: 28527048]
[25]
Bowden J, Smith G, Burgess S. Mendelian randomization with invalid instruments: Effect estimation and bias detection through Egger regression. Int J Epidemiol 2015; 44(2): 512-25.
[http://dx.doi.org/10.1093/ije/dyv080] [PMID: 26050253]
[26]
Bowden J, Holmes MV. Meta-analysis and mendelian randomization: A review. Res Synth Methods 2019; 10(4): 486-96.
[http://dx.doi.org/10.1002/jrsm.1346] [PMID: 30861319]
[27]
Holmes MV, Ala-Korpela M, Smith GD. Mendelian randomization in cardiometabolic disease: Challenges in evaluating causality. Nat Rev Cardiol 2017; 14(10): 577-90.
[http://dx.doi.org/10.1038/nrcardio.2017.78] [PMID: 28569269]
[28]
Yavorska OO, Burgess S. Mendelian Randomization: An R package for performing Mendelian randomization analyses using summarized data. Int J Epidemiol 2017; 46(6): 1734-9.
[http://dx.doi.org/10.1093/ije/dyx034] [PMID: 28398548]
[29]
Tong J, Xu S, Zong H, Pan M, Teng Y, Xu J. Prevalence and risk factors associated with vertebral osteoporotic fractures in patients with rheumatoid arthritis. Clin Rheumatol 2020; 39(2): 357-64.
[http://dx.doi.org/10.1007/s10067-019-04787-9] [PMID: 31691041]
[30]
Kim SY, Schneeweiss S, Liu J, et al. Risk of osteoporotic fracture in a large population-based cohort of patients with rheumatoid arthritis. Arthritis Res Ther 2010; 12(4): R154.
[http://dx.doi.org/10.1186/ar3107] [PMID: 20682035]
[31]
Andreev D, Kachler K, Schett G, Bozec A. Rheumatoid arthritis and osteoimmunology: The adverse impact of a deregulated immune system on bone metabolism. Bone 2022; 162: 116468.
[http://dx.doi.org/10.1016/j.bone.2022.116468] [PMID: 35688359]
[32]
Güler-Yüksel M, Allaart CF, Goekoop-Ruiterman YPM, et al. Changes in hand and generalised bone mineral density in patients with recent-onset rheumatoid arthritis. Ann Rheum Dis 2009; 68(3): 330-6.
[http://dx.doi.org/10.1136/ard.2007.086348] [PMID: 18375540]
[33]
Güler-Yüksel M, Bijsterbosch J, Goekoop-Ruiterman YPM, et al. Changes in bone mineral density in patients with recent onset, active rheumatoid arthritis. Ann Rheum Dis 2008; 67(6): 823-8.
[http://dx.doi.org/10.1136/ard.2007.073817] [PMID: 17644545]
[34]
Raterman HG, Lems WF. Pharmacological management of osteoporosis in rheumatoid arthritis patients: A review of the literature and practical guide. Drugs Aging 2019; 36(12): 1061-72.
[http://dx.doi.org/10.1007/s40266-019-00714-4] [PMID: 31541358]
[35]
Wang Y, Zhao R, Gu Z, et al. Effects of glucocorticoids on osteoporosis in rheumatoid arthritis: A systematic review and meta-analysis. Osteoporos Int 2020; 31(8): 1401-9.
[36]
Liu YQ, Liu Y, Chen ZY, Li H, Xiao T. Rheumatoid arthritis and osteoporosis: A bi-directional Mendelian randomization study. Aging 2021; 13(10): 14109-30.
[http://dx.doi.org/10.18632/aging.203029] [PMID: 34015765]
[37]
Nelson MR, Johnson T, Warren L, et al. The genetics of drug efficacy: Opportunities and challenges. Nat Rev Genet 2016; 17(4): 197-206.
[http://dx.doi.org/10.1038/nrg.2016.12] [PMID: 26972588]
[38]
Deng Y, Wong MCS. Association between rheumatoid arthritis and osteoporosis in Japanese populations: A Mendelian Randomization study. Arthritis Rheumatol 2023; 75(8): 1334-43.
[http://dx.doi.org/10.1002/art.42502] [PMID: 37039764]
[39]
Black DM, Geiger EJ, Eastell R, et al. Atypical femur fracture risk versus fragility fracture prevention with bisphosphonates. N Engl J Med 2020; 383(8): 743-53.
[http://dx.doi.org/10.1056/NEJMoa1916525] [PMID: 32813950]
[40]
Gómez-Vaquero C, Hernández JL, Olmos JM, et al. High incidence of clinical fragility fractures in postmenopausal women with rheumatoid arthritis. A case-control study. Bone 2023; 168: 116654.
[http://dx.doi.org/10.1016/j.bone.2022.116654] [PMID: 36584785]
[41]
Catrina A, Krishnamurthy A, Rethi B. Current view on the pathogenic role of anti-citrullinated protein antibodies in rheumatoid arthritis. RMD Open 2021; 7(1): e001228.
[http://dx.doi.org/10.1136/rmdopen-2020-001228] [PMID: 33771834]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy