Microstructural bone changes biomarker for autoimmunity and RA

By Scott Cunningham, MD, PhD
Published March 30, 2022

Key Takeaways

  • Microstructural bone changes in patients at-risk for rheumatoid arthritis (RA) are a biomarker for autoimmunity and incipient RA.

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.

Why This Study Matters

It has not been previously been established if bone changes predict the onset of RA. The findings of this study clearly support the benefits of validated biomarkers in surveillance for chronic diseases.  Specifically, microstructural bone and joint changes in patients at-risk for RA identified patients at high-risk for RA and the underlying autoimmune activity.

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 (Source).

  • Citrullinated vimentin induces autoantibody formation, which in turn directly induces bone loss (Source).

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