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Bone loss before the clinical onset of rheumatoid arthritis in subjects with anticitrullinated protein antibodies
  1. Arnd Kleyer1,
  2. Stephanie Finzel1,
  3. Jürgen Rech1,
  4. Bernhard Manger1,
  5. Manuel Krieter1,
  6. Francesca Faustini1,
  7. Elisabeth Araujo1,
  8. Axel J Hueber1,
  9. Ulrike Harre1,
  10. Klaus Engelke2,
  11. Georg Schett1
  1. 1Department of Internal Medicine 3, Rheumatology and Immunology, University of Erlangen-Nuremberg, Erlangen, Germany
  2. 2Institute of Medical Physics, University of Erlangen-Nuremberg, Erlangen, Germany
  1. Correspondence to Professor G Schett, Department of Internal Medicine 3, Rheumatology and Immunology, University of Erlangen-Nuremberg, Krankenhausstrasse 12, Erlangen D-91054, Germany; georg.schett{at}


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/cm3) 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%).

Discussion 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.

  • anti-citrullinated protein antibodies
  • bone loss
  • rheumatoid arthritis

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