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Modeling Osteoporosis: Parathyroid Hormone Receptor Binding Kinetics

Carolyn R. Cho
Bioinformatics and Bone & Cartilage Biology
SmithKline Beecham Pharmaceuticals R&D
King of Prussia, PA 19406, USA
Carolyn_R_Cho@sbphrd.com

 

Joint work with Vincent Lemaire, Larry D. Greller, Frank L. Tobin, George Stroup, and Larry J. Suva.

The need for therapeutic agents to treat osteoporosis has focused research on anabolic agents which stimulate bone formation. One of the most potent bone forming agents is parathyroid hormone (PTH), when is it delivered intermittently. However, continuous PTH infusion is destructive to bone. We believe that the anabolic activity of pulsatile PTH is fundamentally a phenomenon mediated by the kinetics of PTH binding to its PTH receptor in osteoblasts, the cell population responsible for formation of bone. We show that plausible PTH receptor binding kinetics, based on a Segel, et al., J. Theoret. Biol. (1986) scheme for receptor-mediated adaptation to stimuli, can discriminate pulsatile from continuous dosing. These studies will provide important insight into the mechanisms underlying skeletal remodeling, which are the basis for the treatment of metabolic bone disease.

 

Connecting Women in Mathematical Sciences to Industry

2000-2001 Program: Mathematics in Multimedia
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