title: Bone loss before the clinical onset of rheumatoid arthritis in subjects with anticitrullinated protein antibodies.
abstract: OBJECTIVE
  Anticitrullinated protein antibodies (ACPA) are a major risk factor for bone loss in rheumatoid arthritis (RA). We have recently shown that ACPA directly induce bone loss by stimulating osteoclast differentiation. As ACPA precede the clinical onset of RA by years, we hypothesised that ACPA positive healthy individuals may already show skeletal changes.
  
  
  METHODS
  We performed a comparative micro-CT analysis of the bone microstructure in the metacarpophalangeal joints of ACPA positive and ACPA negative healthy individuals without clinical signs of arthritis.
  
  
  RESULTS
  ACPA positive (n=15) and negative (n=15) healthy individuals were not different in age (48.2±4.1 vs 51.4±3.8 years, p=0.57) or gender (eight women and two men in both groups). Bone mineral density was significantly reduced in ACPA positive individuals (mean±SEM 280±11 mg/cm(3)) compared with controls (327±6). Bone loss was based on cortical bone changes, with significant (p=0.044) reduction in cortical thickness in the ACPA positive group (mean±SEM 0.22±0.03 mm) compared with controls (0.32±0.03 mm). Areas of cortical porosity were significantly (p=0.0005) more widespread in ACPA positive (mean±SEM 7.4±1.4%) than in ACPA negative individuals (1.0±0.3%).
  
  
  CONCLUSIONS
  Structural bone damage starts before the clinical onset of arthritis in subjects with ACPA. These findings revise the concept that bone damage is an exclusive consequence of synovitis in patients with RA.
authors.affiliation: Department of Internal Medicine 3, Rheumatology and Immunology, University of Erlangen-Nuremberg, , Erlangen, Germany.
authors.forename: Arnd
authors.initials: A
authors.lastname: Kleyer
authors.forename: Stephanie
authors.initials: S
authors.lastname: Finzel
authors.forename: Jürgen
authors.initials: J
authors.lastname: Rech
authors.forename: Bernhard
authors.initials: B
authors.lastname: Manger
authors.forename: Manuel
authors.initials: M
authors.lastname: Krieter
authors.forename: Francesca
authors.initials: F
authors.lastname: Faustini
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Araujo
authors.forename: Axel J
authors.initials: AJ
authors.lastname: Hueber
authors.forename: Ulrike
authors.initials: U
authors.lastname: Harre
authors.forename: Klaus
authors.initials: K
authors.lastname: Engelke
authors.forename: Georg
authors.initials: G
authors.lastname: Schett
mesh_terms: D001172:Arthritis, Rheumatoid / Q000097:blood / Q000000981:diagnostic imaging* / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D008662:Metacarpophalangeal Joint / Q000000981:diagnostic imaging; D008875:Middle Aged; D055114:X-Ray Microtomography
chemical_list: D001323:Autoantibodies; D001324:Autoantigens
keywords: anti-citrullinated protein antibodies; bone loss; rheumatoid arthritis