Alveolar bone loss is associated with circulating anti-citrullinated protein antibody (ACPA) in patients with rheumatoid arthritis

J Periodontol. 2015 Feb;86(2):222-31. doi: 10.1902/jop.2014.140425. Epub 2014 Oct 9.


Background: This study examines: 1) alveolar bone loss (ABL), a hallmark of periodontitis, in anti-citrullinated protein antibody (ACPA)-positive rheumatoid arthritis (RA) patients versus control patients with osteoarthritis (OA); and 2) the association of ABL with RA disease activity and ACPA concentrations, including multiple antigen-specific ACPA.

Methods: This multicenter case-control study includes 617 patients diagnosed with RA (n = 287) or OA (n = 330). Panoramic radiographs were taken; patients were categorized into low, moderate, or high tertiles based on mean percentage ABL. Serum ACPA was measured using second-generation anticyclic citrullinated peptide enzyme-linked immunosorbent assay and a multiplex platform to assess distinct antigen-specific ACPA. A generalized linear mixed model for binary data was used to compare stratified ABL in RA versus OA patients. Associations of moderate and high ABL (versus low) with RA disease activity and severity measures were examined using multivariate regression. Antigen-specific ACPA responses were compared among ABL tertiles using significance analysis of microarrays.

Results: ACPA-positive patients with RA had a significantly higher mean percentage of sites with ABL >20% compared with patients with OA (P = 0.03). After multivariate adjustment, greater ABL was significantly associated with higher serum ACPA concentration (P = 0.004), 28-joint Disease Activity Score (P = 0.023), health assessment questionnaire disability (P = 0.05), tender joint count (P = 0.02) and joint space narrowing scores (P = 0.05) among patients with RA. ACPAs targeting citrullinated vimentin and histone were significantly higher in moderate and high ABL groups versus low, regardless of smoking status (q <0.1%).

Conclusions: Greater ABL was associated with higher ACPA, consistent with findings at articular sites. ACPA targeting could provide novel insight into important linkages between RA and periodontitis.

Keywords: Alveolar bone loss; arthritis, rheumatoid; histones; peptides, cyclic; periodontitis; vimentin.

Publication types

  • Comparative Study
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alveolar Bone Loss / immunology*
  • Arthritis, Rheumatoid / blood*
  • Arthritis, Rheumatoid / diagnostic imaging
  • Arthritis, Rheumatoid / immunology
  • Autoantibodies / blood*
  • Autoantigens / blood
  • C-Reactive Protein / analysis
  • Case-Control Studies
  • Disease Progression
  • Female
  • HLA-DRB1 Chains / blood
  • Hand Joints / diagnostic imaging
  • Histones / blood
  • Humans
  • Male
  • Middle Aged
  • Osteoarthritis / blood
  • Osteoarthritis / diagnostic imaging
  • Osteoarthritis / immunology
  • Peptides, Cyclic / blood*
  • Peptides, Cyclic / immunology
  • Radiography
  • Rheumatoid Factor / blood
  • Smoking / immunology
  • Vimentin / blood
  • Wrist Joint / diagnostic imaging


  • Autoantibodies
  • Autoantigens
  • HLA-DRB1 Chains
  • Histones
  • Peptides, Cyclic
  • Vimentin
  • cyclic citrullinated peptide
  • C-Reactive Protein
  • Rheumatoid Factor