Juxta-articular, peri-articular, and systemic bone loss occur in both RA and in the rat CIA model, driven primarily by direct increases in the pro-resorptive mediator RANKL and secondarily by increases in IL-1 and TNF, which can increase resorption both directly, as well as secondarily by inducing RANKL production (Redlich, 2012). This evidence concerns the gene TNF and rheumatoid arthritis.