No Bones About It

Anyone prescribed steroids such as cortisone for arthritis and other autoimmune conditions has probably been warned by the doctor that the drugs can weaken bones. Despite the caveat, scientists weren't really sure why this happened. Now, a new study suggests that cortisone prevents strong new bone from forming because it disables cells that break down old bone. The findings could help researchers find a way to block one of steroids' most devastating side effects.

Doctors prescribe high doses of a class of steroids called glucocorticoids to treat asthma, rheumatoid arthritis, and a number of other inflammatory and autoimmune diseases. Transplant patients also use the drugs to help thwart organ rejection. But the medication can cause patients to lose about 12% of their bone mass during the first year and about 3% every year after that.

Scientists suspected that steroids interfere with the process of bone remodeling, in which cells called osteoclasts continuously break down old bone while other cells called osteoblasts build new bone. (Old bone must be broken down first, otherwise the new bone that is added will be of inferior quality.) Studies with bone-building osteoblasts have produced conflicting results, however: In animal models, scientists found that cortisone dismantles osteoblasts, suppressing bone formation. But studies in cell culture showed that the drug fuels bone growth.

So Steven Teitelbaum, a bone cell biologist at Washington University School of Medicine in St. Louis, Missouri, decided to focus instead on the bone dismantlers, the osteoclasts. Working with fellow Washington University scientist Louis Muglia, Teitelbaum developed a line of transgenic mice with modified osteoclasts: The cells still functioned normally, but they lacked steroid receptors. When the researchers gave high doses of cortisone to these mice, the mice built typically strong and healthy bones. Mice with normal osteoclasts, however, produced inferior bones when given high doses of cortisone.

"This is a very elegant study that brings a new dimension to our understanding of glucocorticoid-induced osteoporosis," says Gerard Karsenty, a geneticist at Columbia University. The findings could aid scientists searching for therapies for such ailments as osteoporosis, says Teitelbaum, whose team reports its results today in the Journal of Clinical Investigation.

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