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Bone Disorder Finding - 2002-01-12

Researchers have found the cause of a rare bone disorder in children that may eventually lead to a treatment for osteoporosis, a common disease that causes weak and brittle bones in the elderly.

Researchers at Johns Hopkins University School of Medicine in Baltimore, Maryland, and three other centers found that defects in a gene that's sensitive to hormones can lead to progressive osseus heteroplasia, or POH.

"I think that this disease, progressive osseus heteroplasia, represents a model for us to understand the factors, genetic and biochemical, that may trigger the development of new bone," says Michael Levine, a professor of pediatrics and medicine at Johns Hopkins. Dr. Levine headed a multi-center study that looked at the hormone sensitive gene, GNAS. The investigators found that children with POH had defects in GNAS that results in the production of too little of a protein called Gs-alpha, which plays a critical role in cells' ability to communicate with other cells.

The result, according to Dr. Levine, is a communication breakdown. "This unusual syndrome is an example of a disorder in biology where a patient begins to grow bone in places where there shouldn't grow bone. And the bone is absolutely normal except for its location," he says. "And what it represents is a mis-wiring of signals that regulate primitive cells and differentiation, so that cells that should become muscle and connective tissue, or fat or even skin somehow are being triggered to become bone cells."

By understanding the mechanism by which children with POH produce too much bone tissue, researchers think they may be able to strengthen the frail bones of osteoporosis patients. Again, John's Hopkins' University's Dr. Michael Levine. "Ultimately we can learn how bone regenerates, and what signals cause primitive cells to generate into bone cells, we may be able to develop rational therapies that we can then apply to osteoporosis," he says.

Dr. Levine and colleagues published their work on POH in the "New England Journal of Medicine."

The disorder strikes approximately one in 100,000 children. Doctors at Washington University in St. Louis, Missouri sent the genetic material from two children to Baltimore to be analyzed. Dr. Michael Whyte, a co-author of the New England Journal Study, says researchers made a fascinating finding. "A very wonderful revelation came from the clinical investigation concerning a genetic phenomenon known as imprinting, where depending upon whether you inherit a gene defect from either parent, depending upon whether it's coming from a mother or father, you can end up with a different expression of a disorder," he says. "And that's what's talked about in this paper. At last an explanation based on imprinting based on who might develop POH and who might develop Albright's hereditary osteo-dystrophy."

Until researchers looked closely at the genes of children with what appeared to be different bone overgrowth diseases, doctors thought they were separate disorders. They have discovered otherwise.