(LITTLE ROCK, AR) -- Scientists at the University of Arkansas for Medical Sciences (UAMS) and Central Arkansas Veterans Healthcare System (CAVHS) have published findings in The Journal of Clinical Investigation (JCI) on the mechanism of bone regeneration that could change the nature of research into a cure for osteoporosis.
In an accompanying JCI commentary, Janet Hock of Lilly Research Labs in Indianapolis concluded, "[UAMS/VA researchers] have contributed to our understanding that apoptosis may have a role in the varied mechanisms by which PTH regulates [bone regeneration]."
"Osteoporosis, the disease that results from bone loss, causes bone fractures in millions of elderly people worldwide. All existing therapies for osteoporosis only prevent or retard additional bone loss. None of these drugs is capable of rebuilding bone after it is lost. Our findings redefine the course for future drug discovery in the treatment of osteoporosis," said Stavros C. Manolagas, MD, Ph.D., director of the Division of Endocrinology and Metabolism at the Center for Osteoporosis and Metabolic Bone Diseases. "No longer are we talking about just treating this disease; this research has opened a pathway to a cure."
First author of the paper, Robert L. Jilka, Ph.D., CAVHS research scientist and UAMS professor, explained that it has been known for a long time that parathyroid hormone (PTH), a hormone normally made in the body--when it is given as daily injections--stimulates bone formation. But, it wasn't known how it worked. "Now we know that it works by inhibiting apoptosis, the programmed death of cells in bone-forming cells. It has long been known that PTH--given to animals and humans--forms new bone, but it has been a mystery as to how it does so. What we discovered is that PTH extends the life of osteoblasts -- the cells that create new bone tissue -- and therefore enables these cells to build more bone tissue."
"Because the adult human skeleton is continually renewed throughout life, every day, teams of bone-destroying cells (osteoclasts) and bone-forming cells (osteoblasts) restore bone. Like road crews at millions of locations, osetoclasts remove weak old bone, and osteoblasts rebuild the skeletal 'asphalt' with patches of new bone tissue," Jilka said.
"Once their mission is fulfilled, the majority of osteoblasts die. We thought if we could keep the bone-forming cells alive longer, we could build up bone mass in people with weak bones, PTH does that and prevents osteoblast death," he said.
Manolagas said that the discovery has implications for ongoing research to develop treatments and cures for other organ diseases, such as heart failure, that are thought to be caused by cell degeneration.
Four other research team members who are co-authors in this paper include Robert S. Weinstein, MD; Teresita Bellido, Ph.D.; Paula Roberson, Ph.D.; and A. Michael Parfitt, MD. In their findings, the authors concluded, "The increased bone mass is most likely the cumulative result of the repeated daily postponement of apoptosis over several generations of osteoblasts."
"Our faculty has made a very important discovery that impacts the well being of millions of people all over the world. It paves the way for the solution of a medical problem that has reached epidemic proportions," said UAMS Executive Vice Chancellor and Dean of the College of Medicine, I. Dodd Wilson, MD. He added, "Thanks to the partnership of the UAMS College of Medicine and the Central Arkansas Veterans Healthcare System, we have on our campus one of the largest and most successful centers for osteoporosis and metabolic bone diseases in the country. We are very proud of this."
The research was supported by National Institutes of Health and Department of Veterans Affairs. The research team, jointly established by the VA and UAMS, has long been involved in the study of osteoporosis. On September 22, 1999, Manolagas will receive the AlliedSignal Award for Research on Aging for his work toward finding an osteoporosis cure. The award, cosponsored by AlliedSignal Corp. and the Alliance for Aging Research, provides $200,000 for future research.
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Media contact: Bonnie Brandsgaard 501-686-8013 [email protected]
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