Estrogen deprivation therapy with aromatase inhibition also results in states of bone turnover similar to these models; thus, these findings provide a theoretical basis for the hypothesis that estrogen deprivation induced by AI therapy stimulates osteoclastic bone resorption, secretion of excess TGF-β, and may potentiate muscle dysfunction through oxidation of RyR1 and resultant Ca2+ leak in patients with early-stage breast cancer. This evidence concerns the gene RYR1 and breast carcinoma.