TNFRSF11A and osteosarcoma: The authors explained this negative result as the effect of zoledronate on immunological parameters such as NK-cell expansion, macrophage depletion, or polarization may affect the bone microenvironment; the absence of benefit with zoledronate combined with chemotherapy may be related to a potential upregulation of RANK expression that promotes osteosarcoma pathogenesis by osteosarcoma cells[86,25,87].