Association Between Systemic Lupus Erythematosus and Osteoporosis: a Mendelian Randomization Analysis

Overview

Journal BMC Rheumatol

Specialty Rheumatology

Date 2024 May 6

PMID 38711124

Authors

Danfeng Xu

Bing Wu

Affiliations

Soon will be listed here.

Abstract

Background: Systemic Lupus Erythematosus (SLE) and Osteoporosis are two prevalent medical conditions. Previous studies have suggested a possible correlation between SLE and osteoporosis, though the underpinning causal relationship remains largely unknown. The current study aimed to elucidate the causal association between SLE and osteoporosis by employing a Mendelian randomization (MR) approach.

Methods: We performed two-sample MR analysis using the inverse variance-weighted (IVW), weighted median, and MR-Egger methods on publicly available summary statistics datasets using a SLE genome-wide association study (GWAS) as an exposure and osteoporosis GWASs in people with East Asia ancestry as outcomes. The pleiotropy and heterogeneity were examined using a variety of techniques, including the MR-Egger intercept, the MR-PRESSO approach, and the Cochran's Q test.

Results: We selected 26 single-nucleotide polymorphisms from a SLE GWAS as instrumental variables for osteoporosis. The IVW (p < 0.05) method results support a potential association between SLE and osteoporosis. MR-Egger intercept (p = 0.82) and MR-PRESSO global test (p = 0.80) did not suggest evidence of horizontal or directional pleiotropy. Cochran's Q test (p = 0.78) showed that there was no heterogeneity between IVs.

Conclusion: The results of MR analysis indicated that SLE is likely associated with an increased risk of osteoporosis incidence. Our findings highlight the need for increased awareness the potential risk of osteoporosis among SLE patients.

References

Fava A, Petri M . Systemic lupus erythematosus: Diagnosis and clinical management. J Autoimmun. 2018; 96:1-13. PMC: 6310637. DOI: 10.1016/j.jaut.2018.11.001. View

Rees F, Doherty M, Grainge M, Lanyon P, Zhang W . The worldwide incidence and prevalence of systemic lupus erythematosus: a systematic review of epidemiological studies. Rheumatology (Oxford). 2017; 56(11):1945-1961. DOI: 10.1093/rheumatology/kex260. View

Davies N, Holmes M, Davey Smith G . Reading Mendelian randomisation studies: a guide, glossary, and checklist for clinicians. BMJ. 2018; 362:k601. PMC: 6041728. DOI: 10.1136/bmj.k601. View

Quatrini L, Ricci B, Ciancaglini C, Tumino N, Moretta L . Regulation of the Immune System Development by Glucocorticoids and Sex Hormones. Front Immunol. 2021; 12:672853. PMC: 8260976. DOI: 10.3389/fimmu.2021.672853. View

Lai S, Kuo Y, Liao K . Bone health in patients with systemic lupus erythematosus. Ann Rheum Dis. 2019; 80(11):e179. DOI: 10.1136/annrheumdis-2019-216417. View

Adami G, Fassio A, Rossini M, Caimmi C, Giollo A, Orsolini G . Osteoporosis in Rheumatic Diseases. Int J Mol Sci. 2019; 20(23). PMC: 6928928. DOI: 10.3390/ijms20235867. View

Alele J, Kamen D . The importance of inflammation and vitamin D status in SLE-associated osteoporosis. Autoimmun Rev. 2009; 9(3):137-9. DOI: 10.1016/j.autrev.2009.05.001. View

Sharif K, Watad A, Bragazzi N, Lichtbroun M, Amital H, Shoenfeld Y . Physical activity and autoimmune diseases: Get moving and manage the disease. Autoimmun Rev. 2017; 17(1):53-72. DOI: 10.1016/j.autrev.2017.11.010. View

Burgess S, Butterworth A, Thompson S . Mendelian randomization analysis with multiple genetic variants using summarized data. Genet Epidemiol. 2013; 37(7):658-65. PMC: 4377079. DOI: 10.1002/gepi.21758. View

10.

Kuhn A, Gensch K, Haust M, Meuth A, Boyer F, Dupuy P . Photoprotective effects of a broad-spectrum sunscreen in ultraviolet-induced cutaneous lupus erythematosus: a randomized, vehicle-controlled, double-blind study. J Am Acad Dermatol. 2010; 64(1):37-48. DOI: 10.1016/j.jaad.2009.12.053. View

11.

Kim C, Han K, Jung J, Choi H, Bae E, Ma S . Incidence and risk factors for osteoporotic fractures in patients with systemic lupus erythematosus versus matched controls. Korean J Intern Med. 2019; 36(1):154-163. PMC: 7820659. DOI: 10.3904/kjim.2018.378. View

12.

Ruiz-Irastorza G, Egurbide M, Olivares N, Martinez-Berriotxoa A, Aguirre C . Vitamin D deficiency in systemic lupus erythematosus: prevalence, predictors and clinical consequences. Rheumatology (Oxford). 2008; 47(6):920-3. DOI: 10.1093/rheumatology/ken121. View

13.

Wang Y, Zhang Y, Lin Z, Zhang H, Wang T, Cao Y . Identification of 38 novel loci for systemic lupus erythematosus and genetic heterogeneity between ancestral groups. Nat Commun. 2021; 12(1):772. PMC: 7858632. DOI: 10.1038/s41467-021-21049-y. View

14.

Brance M, Larroude M, Zamora N, Bagur A, Graf C, Giacoia E . Argentine Guidelines for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis in Postmenopausal Women and Men Aged 50 Years and Older. J Clin Rheumatol. 2023; 29(5):e59-e70. DOI: 10.1097/RHU.0000000000001951. View

15.

Hartwig F, Davies N, Hemani G, Davey Smith G . Two-sample Mendelian randomization: avoiding the downsides of a powerful, widely applicable but potentially fallible technique. Int J Epidemiol. 2017; 45(6):1717-1726. PMC: 5722032. DOI: 10.1093/ije/dyx028. View

16.

Cain D, Cidlowski J . Immune regulation by glucocorticoids. Nat Rev Immunol. 2017; 17(4):233-247. PMC: 9761406. DOI: 10.1038/nri.2017.1. View

17.

Gazitt T, Feld J, Zisman D . Implementation of Calcium and Vitamin D Supplementation in Glucocorticosteroid-Induced Osteoporosis Prevention Guidelines-Insights from Rheumatologists. Rambam Maimonides Med J. 2023; 14(2). PMC: 10147402. DOI: 10.5041/RMMJ.10497. View

18.

White L . Osteoporosis Prevention, Screening, and Diagnosis: ACOG Recommendations. Am Fam Physician. 2022; 106(5):587-588. View

19.

Humphrey M, Buckley L . Glucocorticoid-Induced Osteoporosis. Reply. N Engl J Med. 2019; 380(14):1379. DOI: 10.1056/NEJMc1901239. View

20.

Tedeschi S, Kim S, Guan H, Grossman J, Costenbader K . Comparative Fracture Risks Among United States Medicaid Enrollees With and Those Without Systemic Lupus Erythematosus. Arthritis Rheumatol. 2019; 71(7):1141-1146. PMC: 6594862. DOI: 10.1002/art.40818. View