TNFSF11 and osteoporosis: First, RANK-RANKL signaling drives the osteoclastic activity and MCs expressing RANK ligand, directly stimulating the osteoclasts leading to increased bone resorption, thereby causing osteolysis and osteoporosis.10 This stimulation of the osteoclastic activity by the upregulation of RANK ligand also forms the basis of the osteolytic lesions.11 The second mechanism is through the effects of mediators released by MCs.