(LITTLE ROCK, AR) - The November 2 cover of The Journal of Clinical Investigation highlights the findings by Arkansas scientists on the mechanism that prevents bone fractures in commonly used medications, such as Fosamax and Miacalcin.
"We found that these therapies prevent the death of osteocytes, the cells that detect the need for bone repair and transmit signals for its renewal," explained senior author, Teresita Bellido, PhD, assistant professor, and first author, Lilian I. Plotkin, PhD, post-doctoral fellow, University of Arkansas for Medical Sciences (UAMS).
"Osteoporosis, the disease that results from bone loss and causes bone fractures in millions of people worldwide, requires medications--which work to control fractures. We have now found an explanation of why these medications prevent fractures," said Stavros C. Manolagas, MD, PhD, VA Chief of Endocrinology Section and UAMS Director of the Division of Endocrinology and Metabolism at the Center for Osteoporosis and Metabolic Bone Diseases.
The four other research team members are Manolagas; Robert S. Weinstein, MD, VA and UAMS researcher; A. Michael Parfitt, MD; and Paula Roberson, PhD. In the paper, the authors concluded, "The evidence indicates that preservation of the osteocyte network could be one mechanism by which anti-resorptive agents decrease bone fragility."
The researchers examined the hypothesis that anti-resorptive therapies, such as bisphosphonates and calcitonin, suppress the death of osteocytes and osteoblasts. For this purpose they used in vitro cell cultures of bone cells. They discovered that after treating them with these medications, they were protected from death induced by insulting agents. They confirmed that this survival effect also occurred in vivo; thus, when mice were treated with these agents, the prevalence of osteocyte/osteoblast death was reduced. The researchers established that these medications rapidly activate intracellular survival signals.
These results suggest that the therapeutic efficacy of anti-resorptive agents may be due in part to their ability to preserve osteocyte and osteoblast integrity.
Their work is supported by the National Institute of Health and the 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 was honored by AlliedSignal for the team's work on discovering new therapies that increase bone mass, in other words, cure, as opposed to manage, of osteoporosis. He received the Research on Aging Award, which provided $200,000 for future research.
"Our faculty has made an important contribution to a medical problem that has reached epidemic proportions," said UAMS Executive Vice Chancellor and Dean of the College of Medicine, I. Dodd Wilson, MD. "Thanks to the partnership of UAMS 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."
"Through the years, VA research has made major contributions toward improving healthcare, not only for veterans, but for all Americans," said Director of the Central Arkansas Veterans Healthcare System, George H. Gray, Jr. "This study demonstrates the commitment of these outstanding investigators to search for cause, treatment and cure of bone disease."
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