The resultant co-inactivation of MAPK and NF-κB by RbCl contributes to inhibit RANKL-stimulated osteoclast formation synergistically, as further evidenced by the downregulated levels of osteoclastic genes and activity of NFATc-1, highlighting that MAPK/NF-κB targeting strategy may serve as a promising approach in the treatment of osteoporosis. The gene discussed is TNFSF11; the disease is osteoporosis.