Originally created 05/16/02

Dense-boned family may hold key to treating osteoporosis



BOSTON -- Scientists studying a family with a strange and rare genetic condition that gives members square jaws and superdense bones have pinpointed a protein that could advance the quest for better osteoporosis drugs.

Current treatments for osteoporosis, like calcium and hormones, largely focus on preventing bone loss. But doctors are looking for better ways to actually build bone, especially in patients with severe loss.

Bone-weakening osteoporosis affects 10 million Americans - most of them women - and leads to more than 1.5 million fractures a year, according to the National Institutes of Health.

Researchers at Yale University focused on a family with the opposite problem: bones about twice as dense as usual. Their genetic condition is so rare it is unnamed.

It gives family members square jaws and bony growths on the roofs of their mouths. It does not impair their daily lives, other than making it difficult to float.

The condition was discovered in the family when a middle-aged member got into a serious traffic accident.

"They took routine X-rays, and he had unbelievably dense bones - no fractures," said Dr. Richard Lifton, leader of the research team.

The researchers, who reported their findings in Thursday's New England Journal of Medicine, first found that the family members all carried a mutation of a gene known as LRP5. They were also found to have unusually high levels of bone-building proteins.

The researchers then located a specific protein, called Dkk-1, that appears to act as a brake on the bone-building chemical process set in motion by LRP5.

They reasoned that if the Dkk-1 protein could be altered by a drug so it no longer brakes this bone-building process, osteoporosis patients could form new bone.

"What's so exciting about this is it points to a system that seems to build bones," said Dr. Karl Insogna, a bone specialist on the research team. "It provides a direct molecular target."

Already, at least one drug developed for osteoporosis seems to build bone, but it is not clear exactly how it works.

In an accompanying editorial, two doctors at Baylor College of Medicine in Houston, Millan Patel and Gerard Karsenty, cautioned that more study is needed to know if it is practical to disable the Dkk-1 protein.

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On the Net:

http://www.nejm.org for New England Journal of Medicine

http://www.niams.nih.gov/hi/topics/osteoporosis/opbkgr.htm for background on osteoporosis