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. 2025 May 16;27(1):106.
doi: 10.1186/s13075-025-03567-y.

Vagotomy and the incidence of rheumatoid arthritis and osteoarthritis: a Danish register-based study

Matthew C Baker  1 , Dávid Nagy  2 , Suzanne Tamang  3 , Erzsébet Horváth-Puhó  2 , Henrik Toft Sørensen  2   4
Affiliations

Vagotomy and the incidence of rheumatoid arthritis and osteoarthritis: a Danish register-based study

Matthew C Baker et al. Arthritis Res Ther. .

Abstract

Objectives: Given the potential role of vagus nerve stimulation in treating rheumatoid arthritis (RA), we examined the incidence of RA and osteoarthritis (OA) in patients who underwent different forms of vagotomy that disparately affect the inflammatory reflex.

Methods: Using nationwide health registries, we constructed cohorts of patients in Denmark who underwent truncal or superselective vagotomy between 1977 and 1995 and comparison members from the general population matched 10:1 on birth year, sex, and calendar year. We identified incident RA or OA and used Cox proportional hazards models to compute adjusted hazard ratios (aHRs) and corresponding 95% CI.

Results: Our cohorts consisted of 2,260 truncal vagotomy patients matched with 22,610 comparators, and 3,810 superselective vagotomy patients matched with 38,090 comparators. The incidence rate (IR) of RA per 1,000 person-years (95% CI) in the truncal vagotomy cohort was 10.2 (6.5-15.3) versus 7.2 (6.1-8.4) in the matched comparison cohort. The aHR (95% CI) for RA development was 2.62 (1.47-4.67) in the truncal vagotomy cohort and 1.05 (0.51-2.17) in the superselective vagotomy cohort, with respect to comparison cohorts. The risk of developing OA was not significantly different for either vagotomy cohort compared with comparison cohorts.

Conclusion: Truncal vagotomy was associated with an increased incidence of RA; this association was not observed with superselective vagotomy. No association with either form of vagotomy was seen with OA. These findings support the hypothesis that disruption of vagus nerve signaling impacts the inflammatory reflex and contributes to the development of RA.

Keywords: Osteoarthritis; Rheumatoid arthritis; Rheumatoid arthritis risk; Vagotomy; Vagus nerve; Vagus nerve stimulation.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: This study was reported to the Danish Data Protection Agency (record number 2016-051-000001/ 2234) by Aarhus University. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Cohort selection
Fig. 2
Fig. 2
Cumulative incidence estimates for A. rheumatoid arthritis and B. osteoarthritis in patients who underwent truncal vagotomy compared with comparison subjects from the general population, and for C. rheumatoid arthritis and D. osteoarthritis in patients who underwent superselective vagotomy compared with comparison subjects from the general population. The incidence of RA and OA was calculated with a cumulative incidence function, with death treated as a competing event, and the incidence rate per 1,000 person-years reported
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