Background/Purpose: Periarticular bone loss is a long known and early but yet insufficiently understood phenomenon in patients with rheumatoid arthritis. This study investigated whether autoimmunity against citrullinated proteins is causally involved in triggering focal trabecular bone loss by modifying a standard experimental model of periarticular bone loss in the context of arthritis.

Methods: Antigen induced arthritis (AIA) was induced by methylated bovine serum albumin (mBSA) and modified by mutated citrullinated vimentin (MCV). Periarticular bone loss, subchondral osteoclastogenesis as well as expression of PAD enzyme, bone associated genes and cytokines, were assessed after arthritis induction. Immune cell and osteoclast precursor infiltration were detected in the periarticular bone marrow and the local lymph nodes. In addition, periarticular bone loss was assessed upon challenge of mice with anti-MCV antibodies.

Results: Despite inducing a milder form of arthritis than mBSA, MCV triggered significant periarticular bone loss associated with an increased infiltration of osteoclast precursors and mature osteoclasts in the periarticular bone marrow. MCV enhanced the expression of the osteoclast inducers RANKL and MCSF, the cytokines IL-8, IL-1, IL-6 and TNF-α as well as PAD2 and PAD4 enzymes in the focal bone marrow. In addition, also anti-MCV antibody challenge induced significant periarticular bone loss and osteoclastogenesis in the bone marrow of mice.

Conclusion: Autoimmunity against citrullinated vimentin triggers periarticular bone loss by osteoclast activation in the bone marrow. These findings may explain why periarticular bone loss is already found very early in the disease course of rheumatoid arthritis patients.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/periarticular-bone-loss-in-arthritis-is-induced-by-autoantibodies-against-citrullinated-vimentin/