University of Arkansas for Medical Sciences 8-Jul-98
Library: SCI Keywords: STEROID-INDUCED OSTEOPOROSIS RESEARCH EXPLAINS HOW BONE LOSS OCCURS Description: The 60-year puzzle on why steroid-treated patients suffer continual bone loss is explained by scientists in the July 15 Journal of Clinical Investigation.
EMBARGOED UNTIL JULY 14, 1998 CST 4:00 p.m. CONTACTS: Central Arkansas Veterans Healthcare System, Sharon Palmer (501) 660-2001 UAMS, Bonnie Brandsgaard (501) 686-8013
(Editors: A media resource web page is available at
www.uams.edu/osteoporosis. TV PRODUCERS AND REPORTERS: An animated video, which illustrates this steroid-induced imbalance in bone maintenance, is available by request in Beta-SP and S-VHS formats. PRINT REPORTERS: Color or black-and-white photos of researchers and illustrations are available.)
Research Reveals Why Bone Loss Occurs During Steroid Treatment
LITTLE ROCK, AR - Each year millions of Americans have no choice but to begin and stay on steroid-type medications for life-threatening diseases. Such treatments protect those who receive transplants from rejecting their new organs and help people with chronic conditions such as asthma, rheumatoid arthritis, ulcerative colitis, multiple sclerosis and some blood and kidney diseases to have a normal life. Typically, the therapy is needed for many years.
But no matter what the age or gender of these patients, they all can expect the same side effect from taking steroids--serious bone loss or so called osteoporosis--a condition that slowly weakens the bones and eventually causes fractures. More than one-third of patients taking steroids for more than five years have fractures. For the past 60 years, physicians have known that steroid-induced osteoporosis is one of the medication's side effects, but why it occurs has not been clear until now.
The Central Arkansas Veterans Healthcare System and the University of Arkansas for Medical Sciences announced today that researchers of the UAMS/VAMC Center for Osteoporosis and Metabolic Bone Diseases have uncovered how steroids cause osteoporosis. Their results will appear in the July 15, 1998, issue of the prestigious Journal of Clinical Investigation.
VA Associate Director of Geriatric Research and Education Clinical Center Stavros C. Manolagas, M.D., Ph.D.-UAMS Director of the Division of Endocrinology and Metabolism and the UAMS/VAMC Center for Osteoporosis--said, "The discoveries described in this paper represent an important finding as they open the way to tackle a serious medical dilemma that involves millions of people: how to get the many benefits of steroids without devastating the skeleton. Basically, our findings revealed that when animals or humans take high doses of steroids, not only fewer bone-forming cells are made, but they are dying prematurely. This discovery follows our earlier breakthroughs explaining how women lose bone after menopause and how both women and men develop osteoporosis with old age. It confirms our general idea that the fundamental problem in all forms of osteoporosis is abnormal birth and/or death of bone cells."
Dr. Manolagas went on to say, "One very exciting prospect, now that we know the nature of this particular problem, is the development of 'designer-steroids' that will have the inflammation combating properties of the existing steroids but will not have their bone killing effects; in other words, they will be bone sparing. This idea is similar to what is already a reality in the case of postmenopausal osteoporosis, where physicians now have available for their patients 'designer estrogens' that protect the skeleton, but do not have the breast cancer risk associated with the classical estrogen."
VA Staff Endocrinologist Robert Weinstein, M.D.,--UAMS professor and first author of the paper--explained, "Our study shows that steroid-induced osteoporosis arises from changes in the number of bone cells available to maintain bone. This disrupts the stability of bone, causing eventual fractures and, also, collapse of large joints. No bone is spared from the steroid-induced bone loss, but the effects are more dramatic in the spine and in the hip. Unlike common age- and gender-related types of osteoporosis, this form of the disease occurs at any age, even in children. Not infrequently, patients that took steroids for many years end up in a wheelchair. Yet, a recent survey of physicians, showed that most underestimated the risk of glucocorticoid-induced osteoporosis in men and women. Only 25 percent ranked osteoporosis as one of the top three side effects of high-dose glucocorticoid therapy in a 45-year-old pre-menopausal woman and 8 percent ranked it as one of the top three ! side effects in a 45-year-old man."
Dr. Weinstein said that, "Like all problems, knowing the cause makes it a lot easier to figure out the proper defense. We got our clues first from studies with mice. We found that death of bone forming cells was occurring even in normal bones, but at a very low rate. We were totally amazed when we saw the devastating effect of steroids on the survival of these cells, in sections of bone under the microscope. We repeated the findings over and over again to be certain that they were exactly what we thought we were seeing and there were no quirks in our measurements. We felt very gratified and relieved when we saw exactly the same thing in biopsies from patients that had osteoporosis from taking steroids. I am very pleased that, along with the manuscript that is being published in the Journal of Clinical Investigation, the editors were excited enough about our photomicrographs from patients that they chose them for the cover of the Journal."
Two other team members who are co-authors in this paper, VA Research Scientist Robert Jilka, Ph.D., and UAMS Professor of Medicine Michael Parfitt, M.D., made important contributions to these studies. Dr. Jilka reproduced the findings in a cell culture dish and he found that steroids decreased the birth of new cells. Dr. Parfitt worked out that the rate of cell death caused by steroids was high enough to have the devastating effect seen in the bones.
"Our faculty has made an important discovery that could impact the well being of millions of people all over the world. It suggests an approach to the solution of a medical problem that together with the post-menopausal and age-related form of osteoporosis has reached epidemic proportions," said UAMS Executive Vice Chancellor and Dean of the College of Medicine, I. Dodd Wilson, M.D.
Dr. Wilson 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."
"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 disease." # # #
E-mail contact: Bonnie Brandsgaard, [email protected]
BACKGROUND INFORMATION:
-- Weighing benefits and risks is part of all medical decisions.
-- Loss of bone is one of the fundamental side effects of steroids.
-- Bones are constantly rebuilding themselves.
-- When people lose more bone than their bodies make, this process is called osteoporosis.
-- Osteoporosis is a loss of bone that leads to fragility and accounts for 1.5 million fractures annually in the United States alone.
-- Osteoporosis, "porous bone," is the most common bone disease in the world.
Stavros Manolagas, M.D., Ph.D. VA Associate Director, Geriatric Research and Education Clinical Center Director of the Center for Osteoporosis and Metabolic Bone Diseases and the Division of Endocrinology and Metabolism Professor in the Department of Internal Medicine, UAMS College of Medicine EDUCATION: Medical Degree: University of Athens Medical School, Athens, Greece Ph.D. Degree: University of Manchester, England Residency: Stepping Hill Hospital, Stockport, England Fellowship in Endocrinology: Manchester Royal Infirmary, University of Manchester, England
Robert S. Weinstein, M.D. VA Staff Endocrinologist Director of the Bone Histomorphometry Laboratory of the UAMS/VAMC Osteoporosis Center Professor in the Department of Internal Medicine, Division of Endocrinology and Metabolism, UAMS College of Medicine EDUCATION: Medical Degree: University of Illinois Medical Center Residency: Internal Medicine House Staff Michael Reese Hospital and Medical Center, Chicago Fellowship/Endocrinology: University of Miami School of Medicine, Miami
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