Introduction

Autoimmunity, as evidenced by the presence of anti-modified protein antibodies (AMPAs), has been reported to precede the clinical onset of RA by years. Indeed, AMPA-positive patients without joint signs and symptoms are considered to be at-risk for developing RA, even though not all at-risk patients develop RA.  Moreover, it is thought that anti-citrullinated protein antibodies (ACPAs) trigger osteoclast activity, and ACPA-positive patients exhibit more severe bone changes than ACPA-negative patients. It has not been established, however, if bone changes predict the onset of RA.

Study Design

Seventy-five AMPA- and ACPA-positive patients without joint swelling were enrolled in the study.  The second metacarpal head of each patient was scanned using high-resolution peripheral QCT. Additional bone measurements included the total volumetric bone mineral density (vBMD), trabecular vBMD, and cortical vBMD.

Results and Conclusions

Patients with broad AMPA-positivity had a greater number of microstructural bone changes than patients with narrow AMPA-positivity.  Specifically, there was a higher number of cortical microchannels per joint, and decreased total, trabecular, and cortical vBMD.  In addition, the progression to RA was more rapid in patients with broad AMPA-positivity than narrow AMPA-positivity.   Thus, microstructural bone changes herald the onset of RA in at-risk patients.

Related Research

Consider these findings from similar research studies:

• The increased cortical microchannels that occur in RA patients with broad-spectrum autoimmunity may reflect antibody-mediated osteoclastogenesis (Schett G. Autoimmunity as a trigger for structural bone damage in rheumatoid arthritis. Mod Rheumatol 2017;27:193-7).

• Citrullinated vimentin induces autoantibody formation, which in turn directly induces bone loss (Harre U, Georgess D, Bang H, et al. Induction of osteoclastogenesis and bone loss by human autoantibodies against citrullinated vimentin. J Clin Invest 2012;122:1791-802).

Original Source

Simon D, Kleyer A, Cong D, et al. Microstructural bone changes are associated with broad-spectrum autoimmunity and predict the onset of rheumatoid arthritis. Arthritis Rheum 2022;74:418-26.