The inhibitory effect of E2 is associated with the stimulated secretion of OPG by osteoblasts.[18] Previous studies have focused on the characteristics of thalassemic patients with osteoporosis and their response to therapy with bisphosphonates.[12] Because RANK RANKL and OPG play a significant role in bone resorption and seem to be the principal implicated mechanism for the development of osteoporosis in BTM, we will conduct this prospective study to evaluate the anti-RANKL denosumab versus zoledronic acid on TM induced osteoporosis. Here, TNFRSF11B is linked to osteoporosis.