Karl L. Insogna, M.D. Professor of Internal Medicine Director, Yale Bone Center Department of Internal Medicine 333 Cedar Street P.O. Box 208020 New Haven, CT 06520-8020 USA Email: karl.insogna@yale.edu Telephone: (203) 737-2871

• B.A., University of Connecticut, Storrs, CT, 1972
• M.D. University of Connecticut School of Medicine, 1976

Dr. Insogna is a tenured Associate Professor at Yale and an internationally recognized expert in the field of metabolic bone disease. He is referred patients from around the world. He has published widely on the topic in the field's leading scientific journals and is quoted often in the lay press as well as frequently appearing on radio and television. He was a member of the National Institutes of Health Consensus Conference which established new recommendations for the optimal level of calcium intake for all Americans, now adopted nationwide. He is a leading researcher in the causes of bone loss in such diseases as osteoporosis and primary hyper-parathyroidism and is currently conducting studies in, among other areas, the role of diet in the development of osteoporosis. He was recently elected a Fellow of the American Association for the Advancement of Science.

Dr. Insogna is the Director of the Yale Bone Center, a multidiciplinary group comprised of internists, pediatricians, dietitians, and physical therapists who provide comprehensive care for osteoporosis, Pagets disease of bone and a wide range of inherited and acquired skeletal diseases. The Yale Bone Center is listed by the National Osteoporosis Foundation as a major treatment center in Connecticut for patients with osteoporosis. Office hours are held every Tuesday on Dana 3 (789 Howard Avenue).

Research

Dr. Insogna's clinical work currently focuses on the of the role of circulating cytokines, in particular interleukin-6, in the pathogenesis of bone loss in states of parathyroid excess. A prospective study examining the relationship between circulating levels of pro-resorptive cytokines and bone loss in patients with primary hyperparathyroidism is currently underway.

Dr. Insogna is the Director of the Yale Core Center for Musculoskeletal Disorders. The Center is funded by the NIH and serves to help investigators at Yale develop and study animal models for musculoskeletal disorders. More formation about the Center can be found at the Center's web page.

He has begun studies to extend these initial clinical observations. He has shown that neutralizing interleukin-6 in vivo blocks PTH-induced bone resorption and has observed that PTH-induced IL-6 production is greatly increased following estrogen withdrawal both in vivo and in vitro. In the aggregate, these findings suggest that interdicting the actions of IL-6 in bone may be an effective clinical strategy for preventing PTH-induced bone loss.

Dr. Insogna is also exploring the role of CSF-1 in mediating PTH-induced bone resorption. CSF-1 is the principal colony stimulating factor released by osteoblasts in response to PTH and his group, over the last five years, has undertaken detailed studies on the molecular mechanisms by which PTH induces transcriptional activation of the CSF-1 gene. A newly funded initiative is to explore the effects of CSF-1 on mature osteoclasts. Dr. Insogna has shown that CSF-1 induces rapid and dramatic cytoskeletal effects in osteoclasts and is exploring in detail, the signaling mechanisms responsible for these cytoskeletal changes.

Dr. Insogna, in collaboration with Dr. Jane Kerstetter at the University of Connecticut, is studying the role of dietary protein in bone loss using state-of-the-art stable calcium isotopic techniques.

Selected Recent Publications

1. Grey A, Mitnick MA, Shapses S, Ellison A, Gundberg C, Insogna KI. Circulating levels of interleukin-6 are elevated in primary hyperparathyroidism and correlate with markers of bone resorption. J Clin Endocrinol Metab 10:3450-3454, 1996.
2. Kerstetter J, Caseia D, Mitnick M, Ellison A, Gay L, Liskov T, Carpenter T, Insogna K. Increased circulating levels of parathyroid hormone in healthy young women consuming a protein-restricted diet. Amer J. Clin Nutrit. 66:1188-1196, 1997.
3. Insogna K, Sahni M, Grey A, Tanaka S, Horne W, Neff L, Mitnick M, Levy J, Baron R. Colony-stimulating factor-1 induces cytoskeletal reorganization and c-src-dependent tyrosine phosphorylation of selected cellular proteins in rodent osteoclasts. J. Clin. Invest. 100:2476-2485, 1997.
4. Yao G-Q, Sun B, Hammond E, Spencer E, Horowitz M, Insogna K, Weir E. The cell-surface form of colony stimulating factor-1 (CSF-1) is regulated by osteotropic agents and supports formation of multinucleated osteoclast-like cells. J Biol Chem 273:4119-4128, 1998.

A comprehensive list of Dr. Insogna's publications is available via COS.