Trimethylamine N-oxide and hip fracture and bone mineral density in older adults: The cardiovascular health study

Elam, Rachel; Bůžková, Petra; Barzilay, Joshua I.; Wang, Zeneng; Nemet, Ina; Budoff, Matthew J.; Cauley, Jane A.; Fink, Howard A; Lee, Yujin; Robbins, John A.; Wang, Meng; Hazen, Stanley L.; Mozaffarian, Dariush; Carbone, Laura D

doi:10.1016/j.bone.2022.116431

Cited by 12 publications

(5 citation statements)

References 47 publications

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“…In addition, the results of our analysis after removing the covariate BMI from Model 4 were statistically significant, with more significant differences in BMD between serologically positive and negative respondents. Furthermore, previous studies had suggested that BMI and age may be negatively correlated with BMD and that higher BMI and increasing age may lead to lower BMD in patients ( 33 – 36 ). Therefore, we conducted stratified analyses of the two covariates of BMI and age, with the aim of identifying the degree of influence of BMI and age on our analysis results.…”

Section: Discussionmentioning

confidence: 99%

Seropositive for hepatitis B and C viruses is associated with the risk of decreased bone mineral density in adults: An analysis of studies from the NHANES database

et al. 2023

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BackgroundSome studies had reported that patients with viral hepatitis are at increased risk of reduced bone mineral density and even osteoporosis. However, the interaction between reduced bone mineral density (BMD) and viral hepatitis remains inconclusive. Therefore, our study collected hepatitis test results and bone mineral density from respondents in the NHANES database. The aim of this study was to investigate whether there is an association between hepatitis and a decrease in bone mineral density.MethodsThe respondents with both hepatitis- and BMD-related indicators from the NHANES database in the United States from 2005–2010, 2013–2014, to 2017–2020 were collected for this study. BMD were compared between respondents who were positive and negative for respondents related to hepatitis B and C. BMD was measured using dual-energy X-ray absorptiometry of the femur and lumbar spine. Finally, multiple regression analysis was performed between hepatitis B surface antigen (HBsAg) and hepatitis C RNA (HCV-RNA) and BMD in the respondents.ResultsA total of 15,642 respondents were included in the hepatitis B surface antigen-related survey. Of these, 1,217 respondents were positive for hepatitis B surface antigen. A total of 5111 hepatitis C RNA-related responders were included. Hepatitis C RNA-positive had 268 respondents. According to the results of the multiple regression analysis, the femoral BMD was significantly lower in HBsAg (+) respondents compared to HBsAg (–) respondents: −0.018 (−0.026, −0.009) (P < 0.01). Moreover, spinal BMD was significantly lower in HBsAg (+) respondents compared to HBsAg (–) respondents: −0.020 (−0.030, −0.010) (P < 0.01). According to the results of multiple regression analysis for hepatitis C RNA, HCV-RNA (+) respondents had significantly lower BMD compared to HCV-RNA (–) respondents: −0.043 (−0.059, −0.026) (P < 0.01).ConclusionDuring the analysis of respondents in the NHANES database in the United States, positive tests for hepatitis B surface antigen and hepatitis C RNA were found to be associated with a reduction in BMD. Positive serology for these hepatitis indicators may increase the risk of reduced BMD. Of course, this conclusion still needs to be further confirmed by more large clinical trials.

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Section: Discussionmentioning

confidence: 99%

Seropositive for hepatitis B and C viruses is associated with the risk of decreased bone mineral density in adults: An analysis of studies from the NHANES database

et al. 2023

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“…Research has indicated that higher levels of TMAO, a metabolite of dietary choline produced by gut microbes, are linked to an increased likelihood of hip fractures in elderly individuals. This suggests that increased levels of TMAO could be a contributing factor to bone loss and the risk of fractures among older individuals [ 19 ]. Nevertheless, there is currently scarce knowledge regarding its impact on bone loss in osteoporosis.…”

Section: Discussionmentioning

confidence: 99%

Trimethylamine-N-oxide promotes osteoclast differentiation and oxidative stress by activating NF-κB pathway

Zhao,

Wang,

Qiu

et al. 2024

Aging

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Background: Senile osteoporosis may be caused by an imbalance in intestinal flora and oxidative stress. Trimethylamine-N-oxide (TMAO), a metabolite of dietary choline dependent on gut microbes, has been found to be significantly increased in osteoporosis. However, the role of TMAO in bone loss during osteoporosis remains poorly understood. In this study, we examined the impact of TMAO on osteoclast differentiation and bone resorption in an in vitro setting. Methods: Osteoclast differentiation was induced by incubating RAW 264.7 cells in the presence of Receptor Activator for Nuclear Factor-κB Ligand (RANKL) and macrophage-stimulating factor (M-CSF). Flow cytometry, TRAP staining assay, CCK-8, and ELISA were employed to investigate the impact of TMAO on osteoclast differentiation and bone resorption activity in vitro. For mechanistic exploration, RT-PCR and Western blotting were utilized to assess the activation of the NF-κB pathway. Additionally, protein levels of secreted cytokines and growth factors were determined using suspension array technology. Results: Our findings demonstrate that TMAO enhances RANKL and M-CSF-induced osteoclast formation and bone resorption in a dose-dependent manner. Mechanistically, TMAO triggers the upregulation of the NF-κB pathway and osteoclast-related genes (NFATc1, c-Fos, NF-κB p65, Traf6, and Cathepsin K). Furthermore, TMAO markedly elevated the levels of oxidative stress and inflammatory factors. Conclusions: In conclusion, TMAO enhances RANKL and M-CSF-induced osteoclast differentiation and inflammation in RAW 264.7 cells by activating the NF-κB signaling pathway. These findings offer a new rationale for further academic and clinical research on osteoporosis treatment.

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“…[7] Moreover, red meat reduces the ability of kidneys to excrete TMAO. [6] A multitude of recent studies reports that elevated systemic TMAO levels are linked to an increased risk of the burden of lifestyle diseases, such as coronary syndromes, [8] heart failure, [9] preeclampsia, [10] stroke, [11] osteoporosis, [12] and chronic kidney disease (CKD). [13] Since seafood is generally regarded as healthy food, the high TMAO content in fish has been a puzzling and neglected paradox.…”

Section: Doi: 101002/mnfr202200859mentioning

confidence: 99%

“…[40,56] Concerning the gut microbiota, the content of TMAO and TMA varies in fish and seafood. [34,57] Recent studies demonstrate a dose-dependent association between circulating levels of TMAO and the risk of CVD, [11] fractures, [12] stroke, [11] metabolic syndrome, [58] CKD, [59] and mortality risks. [60][61][62]…”

Section: General Health Benefits Of Regular Fish Consumptionmentioning

confidence: 99%

Consumption of Fish in Chronic Kidney Disease – A Matter of Depth

Mafra

Kemp

Leal

et al. 2023

Molecular Nutrition Food Res

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Fish is an excellent source of 𝝎-3 polyunsaturated fatty acids (PUFAs), amino acids, collagen, vitamins, and iodine and its intake is associated with health benefits, mainly reduces risk of cardiovascular mortality. However, recent studies have shown that fish is also an important source of trimethylamine N-oxide (TMAO), a uremic toxin produced by the gut microbiota that promotes an increased risk of cardiovascular diseases. In patients with chronic kidney disease (CKD), TMAO levels are markedly increased due to gut dysbiosis and reduced kidney function. No study has yet evaluated the effects of a fish-rich diet on TMAO plasma levels and cardiovascular outcomes. This review discusses the pros and cons of a fish-rich diet in patients with CKD -a matter of depth.

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Trimethylamine N-oxide and hip fracture and bone mineral density in older adults: The cardiovascular health study

Cited by 12 publications

References 47 publications

Seropositive for hepatitis B and C viruses is associated with the risk of decreased bone mineral density in adults: An analysis of studies from the NHANES database

Seropositive for hepatitis B and C viruses is associated with the risk of decreased bone mineral density in adults: An analysis of studies from the NHANES database

Trimethylamine-N-oxide promotes osteoclast differentiation and oxidative stress by activating NF-κB pathway

Consumption of Fish in Chronic Kidney Disease – A Matter of Depth

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