# The association between long-term opioid therapy and composite infection-related dental outcomes

**Authors:** Anne C. Black, Kirsha S. Gordon, James D. Dziura, Declan T. Barry, Stephen Crystal, E. Jennifer Edelman, Gretchen Gibson, Michelle Hamilton, Marianne Jurasic, Yu Li, Brandon D.L. Marshall, Melissa Skanderson, Katie Suda, William C. Becker, Kimberly Page, Kimberly Page, Kimberly Page

PMC · DOI: 10.1371/journal.pone.0341361 · PLOS One · 2026-02-02

## TL;DR

Long-term opioid therapy is linked to higher risk of dental infections in veterans, but results vary with dental coverage.

## Contribution

This study identifies a potential class-wide adverse effect of long-term opioid therapy on dental health in a large national cohort.

## Key findings

- LTOT was associated with increased risk of composite infection-related dental outcomes.
- Patients with full dental coverage had higher CIDO rates but no significant LTOT association.
- Results suggest unique vulnerability among veterans with full dental coverage.

## Abstract

The Food and Drug Administration’s warning that transmucosal buprenorphine, a partial opioid agonist used to treat opioid use disorder and chronic pain, may cause dental disease opens questions about potential class-wide adverse effects involving more widely prescribed opioid analgesics.

This was a retrospective matched national cohort study of patients in care at the Department of Veterans Affairs (VA) between October 2010-September 2019. Patients prescribed LTOT were matched 1:2 to patients not prescribed LTOT on age, sex, service region, and VA dental coverage. Cox regression models estimated the association between LTOT and a composite infection-related dental outcome (CIDO). Sensitivity analyses excluded patients with cancer, restricted to patients with comprehensive dental coverage, and to patients with ≥180 days of follow-up time, respectively.

The cohort comprised 2,173,435 patients including 787,825 (36%) receiving LTOT; 612,101 (28%) experienced CIDO. In both simple and multivariable regression models, LTOT exposure was associated with greater CIDO risk; HR (95% CI) =1.24 (1.23, 1.25); aHR (95% CI) =1.08 (1.07, 1.08), respectively; p < 0.001. Sensitivity analyses showed similar results except among patients with full dental coverage for whom CIDO rates were substantially higher and LTOT was not statistically significantly associated with risk.

he observed positive association between LTOT and CIDO in this large VA sample may inform patient-provider discussions and decision-making around use of LTOT. High CIDO rates among patients with full VA dental coverage may reflect their unique vulnerability to dental infection associated with service-related dental or disabling conditions. Limitations include risk for ascertainment bias, unclear generalizability to a broader clinical population, and the potential for residual confounding.

## Linked entities

- **Chemicals:** buprenorphine (PubChem CID 644073)

## Full-text entities

- **Diseases:** diabetes (MESH:D003920), depression (MESH:D003866), dental disability (MESH:D009057), bipolar disorder (MESH:D001714), death (MESH:D003643), cardiovascular disease (MESH:D002318), liver disease (MESH:D008107), COPD (MESH:D029424), Diseases (MESH:D004194), Pain (MESH:D010146), overdose (MESH:D062787), Classification (MESH:D008310), OUD (MESH:D009293), oral disease (MESH:D009059), MH (MESH:C535694), inflammation (MESH:D007249), body mass (MESH:C536030), obesity (MESH:D009765), schizophrenia (MESH:D012559), alcohol use disorder (MESH:D000437), caries (MESH:D003731), CIDO infections (MESH:D007239), stroke (MESH:D020521), mental health condition (MESH:D000071069), periodontitis (MESH:D010518), bacterial infection (MESH:D001424), PTSD (MESH:D013313), CIDO (MESH:D058617), chronic pain (MESH:D059350), HIV (MESH:D015658), drug use disorder (MESH:D019966), major depressive disorder (MESH:D003865), cancer (MESH:D009369), hepatitis C (MESH:D019698), xerostomia (MESH:D014987), tooth loss (MESH:D016388), dental problems (MESH:D019973)
- **Chemicals:** tramadol (MESH:D014147), hydromorphone (MESH:D004091), buprenorphine (MESH:D002047), Suboxone (MESH:D000069479), levorphanol (MESH:D007981), naloxone (MESH:D009270), hydrocodone (MESH:D006853), morphine (MESH:D009020), fentanyl (MESH:D005283), oxycodone (MESH:D010098), meperidine (MESH:D008614), tapentadol (MESH:D000077432), 46805R1 (-), dihydrocodeine (MESH:C014481), propoxyphene (MESH:D011431), methadone (MESH:D008691), pentazocine (MESH:D010423), methamphetamine (MESH:D008694)
- **Species:** Homo sapiens (human, species) [taxon 9606], Human immunodeficiency virus 1 (no rank) [taxon 11676], Human immunodeficiency virus (species) [taxon 12721]

## Full text

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## Figures

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## References

12 references — full list in the complete paper: https://tomesphere.com/paper/PMC12863492/full.md

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Source: https://tomesphere.com/paper/PMC12863492