Marrow transplant fights bone disease.

Children born with a hereditary disease called osteogenesis imperfecta can face a lifetime of bone deformities, fractures, and short stature. These children produce faulty collagen--the white, fibrous protein that forms the framework for bone, tendons, and ligaments.

The skeletons of severely affected children are so weak that parents have been known to break a child's leg accidentally while changing a diaper. There is no known cure for osteogenesis imperfecta. Treatment consists of inserting metal rods into the largest bones as reinforcements.

Now, initial findings in a study of three children with the disease who received bone marrow transplants from healthy siblings reveal sharp increases in the recipients' bone mass, fewer fractures, and some height gain. The work, reported in the March NATURE MEDICINE, raises the prospect of a treatment that attacks osteogenesis imperfecta at its core.

Three months after receiving the marrow transplants, only 1.5 to 2.0 percent of the patients' osteoblasts--cells that make collagen--stemmed from donated marrow. Yet that small amount seems to have made a difference, says study coauthor Edwin M. Horwitz, a pediatric hematologist and oncologist at St. Jude Children's Research Hospital in Memphis, Tenn.

Horwitz admits to being "a bit surprised" when analysis showed that the three children had added 21, 28, and 29 grams of bone in the 100 days after the transplant. Healthy children of these ages--two of the patients were 13 months old and the other 32 months old--showing the same modest weight gain would have been expected to add less than 4 g of bone, he says.

The children chosen for this study were shockingly fragile. One of the 13-month-old infants had already had at least 37 fractures. This baby had only 3 fractures during the 6 months following the marrow transplant. The other 13-month-old baby had had at least 20 fractures before treatment but only 2 during the follow-up period. The third child had had 3 fractures in the 6 months preceding transplant and none during the next 6 months.

During the 6-month follow-up period, the two younger children grew 8.0 and 6.5 centimeters, roughly on a par with healthy babies that age. The older child, who hadn't grown at all during the 6 preceding months, grew 1.5 cm--38 percent of the normal rate.

One in 20,000 babies born in the United States has osteogenesis imperfecta. Those with severe cases--such as the children in the new study--usually don't survive beyond their 20s, Horwitz says. Some with less severe disease live longer, but many need wheelchairs to get around.

Marrow transplants--most commonly used to fight blood cancers and certain genetic diseases--had never been tried against osteogenesis imperfecta for fear that the procedure would place too great a strain on the children. Better transplant techniques have made marrow donation safer, says Stanton L. Gerson, a hematology oncologist at Case Western Reserve University in Cleveland. The treatment seems to work, but until doctors give it to more children, it is "premature to talk about this as a clinical success," he says.