The National
Spinal Cord
Injury Association

Disability in the News.

Study Reveals Why Bone Loss Occurs During Steroid Treatment.

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. 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 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," said Stavros C. Manolagas, M.D., Ph.D., the associate director of the VA Geriatric Research and Education Clinical Center, and UAMS Director of the Division of Endocrinology and Metabolism and the UAMS/VAMC Center for Osteoporosis.

"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," continued Manolagas.

Dr. Manolagas says further, "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 classical estrogen," added Manolagas.

"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," explained Robert Weinstein, M.D., a staff endocrinologist at the VA Central Arkansas Healthcare System. He is also a UAMS professor and first author of the paper.

"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," continued Weinstein.

"Not infrequently, patients who take 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.

"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."

Weinstein said the UAMS/VA team repeated the findings to be certain that they were exactly what they were seeing, and there were no quirks in their measurements. The researchers were gratified and relieved when they saw exactly the same thing in biopsies from patients who had osteoporosis from taking steroids.

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 determined that the rate of cell death caused by steroids was high enough to have the devastating effect seen in the bones.  
 

Back to Disability in the News.

Browse the News Room Archives