Microstructural Bone Changes Linked to Autoimmunity and RA Onset

scanning electron migrograph (SEM) of osteoporosis
scanning electron migrograph (SEM) of osteoporosis
Microstructural changes of the periarticular cortical bone represent a link between symptomatic autoimmunity and rheumatoid arthritis.

Microstructural bone changes in patients considered at-risk for rheumatoid arthritis (RA) are associated with broad-spectrum autoimmunity and are predictive of disease onset, according to research results published in Arthritis & Rheumatology.

Investigators conducted a cross-sectional, longitudinal analysis of bone microstructure and patient autoimmunity both to analyze the nature of microstructural bone changes in RA and to determine whether and how these structural changes might be related to RA-specific autoimmunity. They also sought to address whether these microstructural changes are associated with risk for progression to RA.

The study cohort included 75 patients (mean age, 50.7±1.5 years; 39 women) at risk for RA. To be eligible for inclusion, patients were required to test positive for antibodies against cyclic citrullinated peptide-2 (CCP2) or mutated citrullinated vimentin and have no present or previous signs of joint swelling.

Investigators began with an analysis the participants’ reactivity to antimodified protein antibodies (AMPA), including rheumatoid factor and CCP2 reactivity, as well as antibodies against 3 additional citrullinated peptides and 3 additional protein modifications. The results indicated that 16 participants had narrow reactivity, 23 had medium reactivity, and 36 had broad reactivity (1-2, 3-5, and 6-8 reactivities, respectively). Also, the prevalence of clinically suspect arthralgia was elevated in patients with broad AMPA reactivity.

Researchers then examined whether broad AMPA reactivity is associated with the structural priming of joints. High-resolution computed tomography imaging of the metacarpal head was conducted in all patients, followed by an assessment of cortical microchannels and volumetric bone mineral density of the total, trabecular, and cortical bones. High-quality images were obtained for 58 participants; these patients were not, researchers noted, different from patients for whom no high-quality images could be obtained in terms of age, sex, arthralgia presence, rheumatoid factor level, CCP2 antibodies, and AMPA categories.

Total and radial cortical microchannels, however, were significantly increased in patients with broad AMPA specificity. Microstructural bone changes were also generally more pronounced among patients with higher autoantibody levels, regardless of the nature of the modification.

Bone microstructure in at-risk patients who progressed to RA was compared with those who did not progress. Both total and radial cortical microstructures were significantly different between the 2 groups. Those who progressed had “significantly diminished” total, trabecular, and cortical bone volumes.

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Within the cohort, 23 patients developed RA over a 1-year follow-up period. Patients with broad AMPA specificity demonstrated the highest risk for progression to RA (48%), whereas progression rates were lower in those with medium and narrow AMPA specificities (26% and 0%, respectively). At-risk individuals with high cortical microchannels (>80/joint) also had a higher likelihood of RA progression compared with those with low cortical microchannels (44% vs 10%).

Study limitations included the sample size, resulting from the limited availability of high-resolution computed tomography images, and the inability of investigators to “make definite conclusions about the causality of bone architectural changes and the onset of RA.”

“Taken together, our data suggest that microstructural changes of the periarticular cortical bone represent a link between symptomatic autoimmunity and RA,” the researchers concluded. “These data support the concept of structural priming of joints by autoimmunity before the onset of the inflammatory phase of the disease.”

Disclosure: Holger Bang, PhD, is an employee of Orgentec.


Simon D, Kleyer A, Cong DB, et al. Micro-structural bone changes are associated with broad-spectrum autoimmunity and predict the onset of rheumatoid arthritis [published online February 18, 2020]. Arthritis Rheumatol. doi:10.1002/art.41229