Anti-CCP Antibodies Linked to Hip Osteopenia in Early Rheumatoid Arthritis

In patients with early rheumatoid arthritis, a positive anti-cyclic citrullinated protein antibody status was independently associated with reduced bone density, or osteopenia, affecting specific locations in the hip but not in the spine, according to a study published in Arthritis Research & Therapy.

The investigators of this observational study sought to examine the association of anti-cyclic citrullinated protein antibodies with osteopenia or pain in patients with early rheumatoid arthritis.

The study cohort included 657 patients with newly diagnosed rheumatoid arthritis, defined by a disease duration of 1 year or less, and whose baseline data was extracted from the Better Anti-Rheumatic Pharmacotherapy study. Osteopenia was defined by a z-score ≤1 standard deviation below the mean bone density value measured for lumbar spine and 3 hip locations (the femoral neck, Ward’s triangle, and the greater trochanter). Using a visual analog scale (VAS), unacceptable pain was defined as pain VAS>40 mm. An anti-cyclic citrullinated protein antibody positive status was defined by a titer>25 IU/ml. Multiple logistic regression models were used to analyze the independent association between anti-cyclic citrullinated protein antibodies and osteopenia or pain.

Of 657 patients, 58% tested positive for anti-cyclic citrullinated protein antibodies, 37% had osteopenia in the lumbar spine, 29% had osteopenia in the hip, and 61% had unacceptable pain at diagnosis. Osteopenia affecting hip locations of the femoral neck (P =.016) and Ward’s triangle (P =.003) was significantly more frequent in patients whose tests were anti-cyclic citrullinated protein antibody positive compared with anti-cyclic citrullinated protein antibody negative. This trend was maintained in men whose tests were at any anti-cyclic citrullinated protein antibody titer, but osteopenia in these hip locations was found only in women who had high anti-cyclic citrullinated protein antibody titers (>500 IU/ml). Anti-cyclic citrullinated protein antibody status was not associated with osteopenia in the lumbar spine for either gender. In regression analyses, anti-cyclic citrullinated protein antibodies were independently associated with the risk for osteopenia in the femoral neck and/or Ward’s triangle, but not with unacceptable pain. The analyses showed that specific inflammatory markers, however, were independently associated with pain.

Limitations to the study included the observational design in which causal relationships cannot be inferred. Analysis of subgroups was limited due to a relatively small number of participants. Finally, the bone measurements used in this study only assessed bone mass, not the microstructure or mechanical properties of bone.

Independent of inflammation, high anti-cyclic citrullinated protein antibody titers in patients with early rheumatoid arthritis were associated with osteopenia in the femoral head and Ward’s triangle of the hip, but not in the lumbar spine. The findings did not reveal a relationship between anti-cyclic citrullinated protein antibodies and pain, and future studies should further explore the interactions between antibodies, bone density, and pain.

Reference

Hafström I, Ajeganova S, Forslind K, Svensson B. Anti-citrullinated protein antibodies are associated with osteopenia but not with pain at diagnosis of rheumatoid arthritis: data from the BARFOT cohort. Arthritis Res Ther. 2019;21(1):45.