Due to the fact that chronic inflammation is considered as the primary trigger for bone damage, the discovery of systemic bone loss and bone erosion in healthy ACPA-positive individuals suggests that bone loss and bone resorption precede the clinical onset of inflammation and may be caused not only by inflammation, absent during the pre-clinical phases of RA, but also by autoantibodies such as ACPAs, present long before arthritis [7,83,84,85]. Here, PRTN3 is linked to Arthritis.