BoneKEy Reports | BoneKEy Watch

Anti-citrullin antibodies and bone loss in rheumatoid arthritis

DOI:10.1038/bonekey.2012.155

Investigating the hypothesis that anti-citrullin antibodies (ACPA) may play an important role in bone metabolism and bone loss in rheumatoid arthritis (RA), Harre et al. compared the levels of markers of bone absorption and resorption in RA patients with and without ACPA. Patients with ACPA showed significantly raised levels of several markers of bone resorption, including collagen type I (CTXI).

ACPA did not appear to increase the potential resorptive capacity of individual osteoclasts; instead, the antibodies promoted differentiation of osteoclast precursor cells, leading to an overall increase in the osteoclast population. In vivo studies confirmed that ACPAs with specificity to mutated citrullinated vimentin (MCV), which are RA-specific, induced bone loss in mice due to a significant increase in osteoclast numbers.

Mice that received MCV-ACPAs also showed increased serum levels of CTXI and significantly higher levels of systemic tumor necrosis factor alpha (TNF-α). Antibody exposure was postulated to stimulate release of TNF-α from the spleen cells, which, in conjunction with RANKL and macrophage colony stimulating factor, promoted osteoclastogenesis.

Editor's comment: This pioneering work shows that components of the autoimmune response of RA, which precedes the acute inflammatory state, are directly involved in bone loss. ACPAs directly activate osteoclasts in vitro and bone loss in vivo, whereas ACPA circulating levels correlate with the level of bone resorption. These findings may provide a new biological target to eventually prevent the early development of erosions and bone loss in RA.

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