The pathogenic effects of ACPAs on bone tissue do not appear to be limited to local bone loss; there are also effects on systemic bone loss, and anti-citrullinated vimentin antibodies are associated with increased serum RANKL levels in early untreated RA patients and seem to be capable to induce osteopenia when injected into mice [48,49]. This evidence concerns the gene TNFSF11 and rheumatoid arthritis.