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During the last 40 years, understanding of bone biology and the pathogenesis of osteoporosis, the most common and impactful bone disease of old age, has improved dramatically thanks to basic and clinical research advances, genetic insights from humans and rodents, and newer imaging technologies. Culprits of osteoporosis are no longer a matter of speculation based on in vitro observations. Instead, they can be identified and dissected at the cellular and molecular level using genetic approaches; and their effect on distinct bone envelopes and anatomic regions can be functionally assessed in vivo. The landscape of pharmacotherapies for osteoporosis has also changed profoundly with the emergence of several potent anti-resorptive drugs as well as anabolic agents, displacing estrogen replacement as the treatment of choice. In spite of these major positive developments, the optimal duration of the available therapies and their long-term safety remain matters of conjecture and some concern. Moreover, anti-resorptive therapies are used indiscriminately for patients of all ages on the assumption that suppressing remodeling is always beneficial for bone, but rebound remodeling upon their discontinuation suggests otherwise. In this lecture, I highlight the latest state of knowledge of bone-intrinsic and extrinsic mechanisms responsible for the development of osteoporosis in both sexes; differences between the mechanisms responsible for the effects of aging and estrogen deficiency; and the role of old osteocytes in the development of cortical porosity. In addition, I highlight advances towards the goal of developing drugs for several degenerative diseases of old age at once, including osteoporosis, by targeting shared mechanisms of aging. Ideas discussed were presented by the author in his 2017 Louis Avioli lecture at the annual ASBMR meeting in Denver, CO.
Stavros Manolagas, M.D., Ph.D.
The Thomas E. Andreoli, M.D., MACP Clinical Scholar Chair in Internal Medicine
Distinguished Professor of Medicine and Professor of Orthopedics
Director, Division of Endocrinology and Metabolism
Director, the UAMS/VA Center for Osteoporosis and Metabolic Bone Diseases
Vice Chair for Research
Department of Internal Medicine
University of Arkansas for Medical Sciences
12:00 pm at Van Andel Institute
Conference Room 3104/3105
For questions, please contact Kim Cousineau at 616.234.5684.