Association Between Systemic Immune-inflammation Index and Trimethylamine N-oxide Levels in Peripheral Blood and Osteoporosis in Overweight and Obese Patients

Overview

Journal Front Endocrinol (Lausanne)

Specialty Endocrinology

Date 2025 Feb 28

PMID 40017693

Authors

Lingling Li

Jinyang An

Jia Bai

Yangyang Zhang

Xinsai Li

Haihong Lv

Affiliations

Soon will be listed here.

Abstract

Background: The intricate relationship between systemic immune-inflammation index (SII) and trimethylamine N-oxide (TMAO) in the peripheral blood and osteoporosis (OP) remains unclear. This study aims to investigate variations in the levels of SII and TMAO in the peripheral blood of overweight and obese patients, and examine the associations between these markers, bone mineral density (BMD), and the occurrence of osteoporotic fractures.

Methods: The study enrolled 765 patients aged ≥ 50 years with BMI ≥ 24 kg/m², dividing them into two groups based on visceral fat area (VFA): <100 cm² and ≥100 cm². A corrected regression model analyzed the association of SII, TMAO, BMD, and osteoporotic fractures incidence in patients with central obesity. Receiver operator characteristic (ROC) curves assessed the predictive ability of SII and TMAO for OP screening.

Results: Baseline data showed that patients with VFA ≥ 100 cm² had lower whole body (WB) and lumbar spine (LS) BMD, but higher SII and TMAO levels compared to those with VFA < 100 cm² (p < 0.05). Particularly in the group with VFA ≥ 100 cm, there was an upward trend in SII and TMAO as bone mass decreased. Regression analysis found SII and TMAO negatively correlated with WB, LS, and femoral neck (FN) BMD, and positively correlated with osteoporotic fractures incidence (p < 0.05). Both were independent risk factors for OP, with combined SII and TMAO detection showing high diagnostic efficacy (sensitivity 94.7%, specificity 96.5%).

Conclusion: In overweight and obese patients, particularly those with a VFA ≥ 100 cm², peripheral blood SII and TMAO levels may serve as valuable biomarkers for the early diagnosis of OP, offering potential clinical utility in identifying high-risk individuals.

References

Kim H, Choe J, Kim H, Bae S, Kim B, Lee S . Negative association between metabolic syndrome and bone mineral density in Koreans, especially in men. Calcif Tissue Int. 2010; 86(5):350-8. DOI: 10.1007/s00223-010-9347-2. View

Fujimoto W, Grote M, Bergstrom R, Shuman W . Visceral fat obesity and morbidity: NIDDM and atherogenic risk in Japanese American men and women. Int J Obes. 1991; 15 Suppl 2:41-4. View

Yang Q, Yan D, Wang L, Li K, Liang W, Zhang W . Muscle fat infiltration but not muscle cross-sectional area is independently associated with bone mineral density at the lumbar spine. Br J Radiol. 2022; 95(1134):20210371. PMC: 10996424. DOI: 10.1259/bjr.20210371. View

Thavaraputta S, Dennis J, Ball S, Laoveeravat P, Nugent K . Relation of hematologic inflammatory markers and obesity in otherwise healthy participants in the National Health and Nutrition Examination Survey, 2011-2016. Proc (Bayl Univ Med Cent). 2021; 34(1):17-21. PMC: 7785136. DOI: 10.1080/08998280.2020.1799482. View

Yuan Y, Gan C, Wang M, Zou J, Wang Z, Li S . Association of serum trimethylamine N-oxide levels and bone mineral density in type 2 diabetes mellitus. Endocrine. 2024; 84(3):958-968. DOI: 10.1007/s12020-024-03699-2. View

Ng A, Melton 3rd L, Atkinson E, Achenbach S, Holets M, Peterson J . Relationship of adiposity to bone volumetric density and microstructure in men and women across the adult lifespan. Bone. 2013; 55(1):119-25. PMC: 3650114. DOI: 10.1016/j.bone.2013.02.006. View

Lin H, Liu T, Li X, Gao X, Wu T, Li P . The role of gut microbiota metabolite trimethylamine N-oxide in functional impairment of bone marrow mesenchymal stem cells in osteoporosis disease. Ann Transl Med. 2020; 8(16):1009. PMC: 7475507. DOI: 10.21037/atm-20-5307. View

Chen H, Yi Y, Zhang S, Xu H, Fang X, Tao-Hu . Sarcopenic obesity defined by visceral adiposity was associated with osteoporotic vertebral fracture. Arch Osteoporos. 2022; 17(1):41. DOI: 10.1007/s11657-022-01087-9. View

Tu Y, Yang R, Xu X, Zhou X . The microbiota-gut-bone axis and bone health. J Leukoc Biol. 2021; 110(3):525-537. DOI: 10.1002/JLB.3MR0321-755R. View

10.

Caballero B . Humans against Obesity: Who Will Win?. Adv Nutr. 2019; 10(suppl_1):S4-S9. PMC: 6363526. DOI: 10.1093/advances/nmy055. View

11.

Du Y, Chen Y, Zhang H, Wang X, Zhang Z . Inverse association between systemic immune-inflammation index and bone mineral density in postmenopausal women. Gynecol Endocrinol. 2021; 37(7):650-654. DOI: 10.1080/09513590.2021.1885642. View

12.

Fischer V, Haffner-Luntzer M . Interaction between bone and immune cells: Implications for postmenopausal osteoporosis. Semin Cell Dev Biol. 2021; 123:14-21. DOI: 10.1016/j.semcdb.2021.05.014. View

13.

He J, Zhang B, Fan Y, Wang Y, Zhang M, Li C . Comparison of bioelectrical body and visceral fat indices and anthropometric measures in relation to type 2 diabetes by sex among Chinese adults, a cross-sectional study. Front Public Health. 2023; 11:1001397. PMC: 10661931. DOI: 10.3389/fpubh.2023.1001397. View

14.

Tang Y, Peng B, Liu J, Liu Z, Xia Y, Geng B . Systemic immune-inflammation index and bone mineral density in postmenopausal women: A cross-sectional study of the national health and nutrition examination survey (NHANES) 2007-2018. Front Immunol. 2022; 13:975400. PMC: 9493473. DOI: 10.3389/fimmu.2022.975400. View

15.

Jomrich G, Paireder M, Kristo I, Baierl A, Ilhan-Mutlu A, Preusser M . High Systemic Immune-Inflammation Index is an Adverse Prognostic Factor for Patients With Gastroesophageal Adenocarcinoma. Ann Surg. 2019; 273(3):532-541. DOI: 10.1097/SLA.0000000000003370. View

16.

Suominen H . Muscle training for bone strength. Aging Clin Exp Res. 2006; 18(2):85-93. DOI: 10.1007/BF03327422. View

17.

Zhang W, Dang K, Huai Y, Qian A . Osteoimmunology: The Regulatory Roles of T Lymphocytes in Osteoporosis. Front Endocrinol (Lausanne). 2020; 11:465. PMC: 7431602. DOI: 10.3389/fendo.2020.00465. View

18.

Zhao Y, Wang C, Qiu F, Liu J, Xie Y, Lin Z . Trimethylamine-N-oxide promotes osteoclast differentiation and oxidative stress by activating NF-κB pathway. Aging (Albany NY). 2024; 16(10):9251-9263. PMC: 11164488. DOI: 10.18632/aging.205869. View

19.

Pinar-Gutierrez A, Garcia-Fontana C, Garcia-Fontana B, Munoz-Torres M . Obesity and Bone Health: A Complex Relationship. Int J Mol Sci. 2022; 23(15). PMC: 9368241. DOI: 10.3390/ijms23158303. View

20.

Massier L, Chakaroun R, Tabei S, Crane A, Didt K, Fallmann J . Adipose tissue derived bacteria are associated with inflammation in obesity and type 2 diabetes. Gut. 2020; 69(10):1796-1806. DOI: 10.1136/gutjnl-2019-320118. View