Mutant Mice Mimic Osteoporosis

A new strain of mice with weak bones and stunted growth may become an important tool for researchers to study how bones gradually disintegrate in people who suffer from osteoporosis. The mice, described in this month's issue of Nature Genetics, also may provide a quick way to screen potential drugs for the disease, a disabling condition that afflicts more than a third of U.S. women over the age of 60.

For years, researchers have been looking for genetic links to osteoporosis. Prime candidates have been a group of proteins called proteoglycans, which regulate the process of maintaining bone mass. Earlier studies ruled out several of these proteins, so researchers at the National Institute of Dental Research (NIDR) in Bethesda, Maryland, and several other institutions focused on a proteoglycan called biglycan.

The team developed a strain of mice deficient in Bgn, the gene that makes biglycan. Although the mice seemed normal at birth, after about 3 months they had less bone growth and bone mass compared to normal mice. After 6 months, their inner bone structures were only half the weight of controls. The bones were shaped slightly differently in the mutant mice, and strength tests showed that Bgn-deficient bones were weaker. "Biglycan is the first bone matrix protein we've found that plays a role in bone formation," says NIDR osteoporosis specialist Marian F. Young, who led the study.

Although scientists are still probing how biglycan influences bone formation, the protein may prove an attractive target for possible osteoporosis drugs, says John Termine, a specialist on the disease at Lilly Research Laboratories in Indianapolis. He cautions, however, that biglycan may not be the primary player in the human form of the disease.