Background: Thalassemia is the most common cause of chronic hemolytic anemia and is correlated with significant morbidity and mortality. Osteoprotegerin (OPG) is an α tumor necrosis factor receptor superfamily glycoprotein that acts as a decoy receptor for the receptor activator of nuclear factor kappa B ligand (RANKL), exerting an antiresorptive bone effect and also play critical roles in hypogonadism associated osteoporosis. Objective: To explore the serum levels of RANKL and OPG in adult Egyptian females with Beta-Thalassemia Major (BTM) and to detect their relations with female hypogonadism.