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Background  Anti-citrullinated protein antibodies (ACPA) have been suggested to have a potential role in both bone loss and pain in rheumatoid arthritis (RA), based on studies in vitro and in animal models. Here we addressed if anti-cyclic citrullinated (anti-CCP) antibodies were associated with osteopenia or pain in patients with RA, at the time for diagnosis.    Methods  Baseline data from the BARFOT (Better Anti-Rheumatic PharmacOTherapy) cohort, which consists of patients with RA with a disease duration of 1 year or less, were analyzed. To be included, they should have been assessed by anti-CCP, dual-energy X-ray absorptiometry (DEXA) of lumbar spine and hip, and/or digital X-ray radiogrammetry (DXR) of the metacarpal bones. Osteopenia was defined as a z-score  <  − 1 SD. Pain VAS > 40 mm, was defined as patient unacceptable pain. Multiple logistic regression analyses were performed to assess whether anti-CCP was independently associated with osteopenia or unacceptable pain.    Results  Of the 657 patients, 65% were women, 58% were anti-CCP positive, 37% had osteopenia in the lumbar spine, and 29% had osteopenia in the hip. Sixty-one percent had unacceptable pain at diagnosis. Patients positive for anti-CCP had significantly more frequently osteopenia in the femoral neck and Ward’s triangle compared with anti-CCP-negative patients ( p  = 0.016 and 0.003, respectively). This difference was found in men at any anti-CCP titer, but in women, osteopenia in these hip locations was found only in those with high anti-CCP titers (> 500 IU/ml). Anti-CCP was not associated with osteopenia in the lumbar spine or the metacarpal bones. In multiple logistic regression analyses, anti-CCP was independently associated with osteopenia in the femoral neck and/or Ward’s triangle but not with unacceptable pain. Instead, inflammatory variables were independently associated with unacceptable pain.    Conclusion  These data show that in patients with early RA, anti-CCP positivity was independently associated with osteopenia in the femoral neck and/or Ward, but not in the lumbar spine. In our patients, we could not confirm a recently suggested association between anti-CCP antibodies and pain. Further studies are necessary to explore the possible clinical relevance of interactions between ACPA, bone, and pain found in vitro and in animal models.

arthritis research and therapy

Anti-citrullinated protein antibodies are associated with osteopenia but not with pain at diagnosis of rheumatoid arthritis: data from the BARFOT cohort