In addition, our findings on the relationship between serum levels of VIP and bone metabolism markers in early arthritis patients are in line with our hypothesis about bone-protective effects of VIP in humans, and also point out that in addition to exerting a direct inhibitory effect on osteoclasts, this neuropeptide seems to regulate the RANK/RANKL/OPG system. Here, TNFRSF11A is linked to arthritic joint disease.