Title: ``Osteoporosis: Therapies and Use of Array Technology to Understand Mechanisms''
Speakers: Henry U. Bryant, Ph.D. and Jude E. Onyia, Ph.D.
Place: KRAN G016; October 29, 2002 Tuesday, 4:30pm


Bone is a complex structure, primarily comprised of mineralized extracellular matrix and a small, but very active, cellular component. Through the action of bone degrading osteoclasts and bone forming osteoblasts, bone regularly turns itself over - repairing old or damage bone and replacing it with newly mineralized matrix. Disorders of bone metabolism, such as osteoporosis, arise from an imbalance of this bone resorbing and bone forming activity. Pharmacological approaches to therapy of bone loss are aimed at inhibiting excessive bone resorption with anti-resorptive agents, or at inducing new formation with bone anabolic agents. A variety of anti-resorptive agents are currently available for therapy of osteoporosis, including: bisphosphonates, selective estrogen receptor modulators (SERMs), calcitonins, estrogens and calcium/vitamin D replacement. The specific pharmacological profile of one SERM, raloxifene, which produced beneficial estrogen-like effects on bone and cholesterol metabolism without producing estrogen-like stimulation of the uterus or mammary tissue, will be reviewed. While anti-resorptive agents are effective at preventing bone loss, effective treatment of osteoporosis requires agents capable of bone anabolic activity. Various bone anabolics have been evaluated in preclinical and clinical studies, including: parathyroid hormone (PTH), fluoride, and various growth factors. The nearest of these bone anabolic agents for clinical availability is PTH, which will also be in detail.

The greatest needs affecting future drug discovery efforts for anti-osteoporosis agents and drugs to battle other bone related diseases is a greater understanding of signaling in bone cells, better biomarkers of bone physiology and a better mechanistic understanding of these drugs which affect bone