Wayne State University School of Medicine researcher receives NIH grant to combat osteoporosis
A Wayne State University School of Medicine researcher has received a $228,000 national grant to investigate the mechanism of a hormone and related peptide in the battle against osteoporosis.
Nabanita Datta, M.S., Ph.D., assistant professor in the Department of Internal Medicine’s Division of Endocrinology and a resident of Ann Arbor, Mich., received the grant from the National Institute of Diabetes and Digestive and Kidney Diseases, a branch of the National Institutes of Health, to investigate the mechanism of MAP kinase phosphatase-1 and the role of parathyroid hormone in the treatment of bone disease.
“We hope to facilitate new and novel therapeutic targets for the prevention and reversal of osteoporosis and bone-related diseases,” Datta said. “Osteoporosis is a major health concern in the United States and globally.”
According to the National Osteoporosis Foundation (NOF), 10 million Americans have the disease and another 34 million are at risk. Sixty-eight percent of those are women. About one in two women and one in four men over age 50 in the United States will break a bone due to osteoporosis. Though most persons with osteoporosis are women, each year 80,000 American men suffer hip fractures, and one-third of them die within a year of the injury.
Data from NOF indicates osteoporosis is the cause of 1.5 million bone fractures annually in the United States. The estimated cost for those fractures is $14 billion. Both the number of osteoporosis fractures and their costs are expected to escalate as the baby boomer generation continues to swell the ranks of the nation’s elderly.
Human bone is a dynamic tissue that is continuously destroyed by osteoclasts (bone-resorbing cells) and renewed by osteoblasts (bone-forming cells). A new therapeutic approach for the treatment of osteoporosis includes anabolic agents that promote “osteoblastic differentiation” that leads to increased bone formation. Parathyroid hormone, or PTH, and PTH-related peptide play crucial roles during skeletal development and remodeling.
“So far, human PTH(1-34), or teriparatide, is the only bone anabolic agent approved by the U.S. Food and Drug Administration for the treatment of osteoporosis,” Datta said. “The effects of this agent on bone formation plateau after two years of therapy and there are limits to its safe use. Among these are hypercalcemia, which means elevated calcium levels in the bloodstream, and hypercalcemia, or elevated calcium levels in urine. Hypercalcemia can lead to a number of symptoms including muscle weakness, joint aches and fatigue. Hypercalciurea can impair kidney function.”
Datta is leading research to better understand the molecular mechanism of MAP kinase phosphatase-1 and ERK-MAP kinase in the PTH and PTHrP anabolic action in bone. Her studies, published in the Journal of Bone and Mineral Research, and recently in Cellular Signaling, demonstrate the involvement of MAP kinases and osteoblast cell cycle regulatory proteins in PTH and PTHrP anabolic action in bone.
“Dissecting the molecular mechanisms of this peptide hormone is essential to understanding bone diseases and minimizing adverse effects,” said Datta, who also is advisor of education in the Endocrinology Post-Doctoral Training Program. “The intent of our research is to contribute to the goal of developing more effective therapeutic strategies and to design new curative targets for patients with bone defects, including osteoporosis.”
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