Established MM therapies such as immunomodulatory drugs and proteasome inhibitors partially exert their activity through the OPG/RANK/RANKL system.39, 40 Hence, targeting the OPG/RANK/RANKL system through specific agents such as raloxifene may have therapeutic potential.41, 42 Raising OPG levels directly by infusion of recombinant OPG (Fc-OPG) suppresses bone resorption.43 Potential concerns over the generation of anti-Fc-OPG and binding to TRAIL has however shifted further development away from Fc-OPG as a RANK inhibitor, to Denosumab, a human monoclonal antibody against RANKL.44, 45. This evidence concerns the gene TNFRSF11B and Miyoshi myopathy.