HSP family members, including HSP70 and HSP90, have been studied extensively in several bone diseases, such as osteosarcomas and osteoarthritis.49 The lower HSP70 expression level in B cells in the context of estrogen deficiency as well as the enhanced HSP70 expression during estrogen treatment suggest that HSP70 might serve as a pivotal regulator in HIF-1α-mediated RANKL production. The gene discussed is HSPA1A; the disease is osteosarcoma.