Osteoporosis and Bone Cell Biology
Our research program is focused on epidemiology, the etiology and treatment of osteoporosis, and on basic bone biology. With Dr. L. J. Melton III of the Division of Clinical Epidemiology, we are following a large random sample of men and women from the community population. We are using serial measurements of hormones and bone densitometry at multiple sites, along with assessment of bone turnover using biochemical markers and fracture assessment to identify risk factors for bone loss and fractures.
With Dr. Sundeep Khosla, we have made detailed metabolic studies on osteoporotic patients in Mayo's Clinical Research Unit to assess pathophysiology. Our methods include calcium balance and kinetics, assessment of bone turnover using bone biochemical markers and bone histomorphometry, and bioassay and immunoassay of hormones and cytokines. Several prospective, randomized clinical trials of various therapeutic agents for osteoporosis have been completed.
In cooperation with Drs. T. C. Spelsberg and Sundeep Khosla, we are actively investigating factors regulating the proliferation, recruitment and differentiation of osteoblasts and osteoclasts. We are particularly focused on the action of estrogen on these cells through both the estrogen receptor alpha and estrogen receptor beta. We have also recently made extensive studies on the new TNF-family molecules involved in the regulation of bone resportion, osteoprotegerin and the osteoprotegerin ligand. We employ virtually all of the standard methods for assessing changes in mRNA and proteins of the various growth factors, cytokines and bone matrix proteins. Currently, we are developing techniques for isolating osteoblasts and osteoclasts from human bone biopsy samples and osteoblast precursors from human bone marrow. In addition, we are quantitating gene transcription and protein production directly using quantitative PCR with other technologies.