Osteoporosis is a significant public health concern that affects over 10 million people in the United States. An additional 33.6 million individuals in the US have osteopenia, or low bone mass. While women are more likely than men to get osteoporosis, 7% of men in the United States over age 50 have osteoporosis. With the aging population, these numbers are likely to increase in the next few decades. Estrogens are important in the development of bone and maintenance of bone mineral density in both men and women. Estrogen receptor a (ERa) and estrogen receptor β (ERβ) have each been detected by several methods in both osteoblasts and osteoclasts, but little is known about their mechanism of action in these cells. In particular, we are lacking the knowledge of which genes are regulated in each bone cell type. The goal of the Krum Lab is to understand the mechanism of action of estrogens in bone cells, especially focusing on the genes regulated by estrogens in osteoblasts and osteoclasts. Understanding the molecular biology of estrogens in bone is critical to preventing and/or treating osteoporosis.
Osteosarcoma is the most common tumor of the bone, which accounts for about 3% of childhood cancers. It is a malignant transformation of normal osteoblasts or osteoblast precursors. Normal osteoblasts express ERa; however, a 2008 study demonstrated that 0/28 osteosarcoma tumors showed expression of estrogen receptor alpha (ERa) by immunohistochemistry. The mechanism and consequences of ERa silencing in the transition from osteoblast to osteosarcoma is not understood. It is thought that sex hormones play a role in the onset of the disease, as more boys than girls get osteosarcoma and the cancer develops at the time of puberty. Because girls are less likely to get osteosarcoma, estrogens may be protective of osteosarcoma.