The delay in resolution of clinical activity of CN despite suppression of cytokines may be due to the uninhibited activation of cytokine-independent RANKL pathway; but also suppression of favourable anti-inflammatory cytokines involved in bone healing (IL-4, IL-10) and worsening of hyperglycemia which, in turn, directly exacerbates the RANKL-NF-κB activity and subsequent osteoclastogenesis [40, 41]. This evidence concerns the gene IL10 and Hyperglycemia.