Indeed, a reduced expression of inflammatory cytokines, such as IL-6, IL-18, IL-1β, and TNF-α by inhibiting different signaling pathways has been observed after administration of ALN in several in vitro and in vivo models of arthritis and inflammation43–46, and a reduction of prostaglandin E2 levels in SF was correlated with the decrease of pain in OA patients after intra-articular repeated bisphosphonate administrations47. This evidence concerns the gene IL1B and arthritic joint disease.