Promoting blood vessel growth in bone could treat osteoporosis

The drugs that are on the market to treat osteoporosis work by either blocking cells that break down bone or by boosting osteoblasts—the cells that build bone. Despite the popularity of these drugs, osteoporosis still causes 9 million fractures per year, says the International Osteoporosis Foundation.

Researchers at Weill Cornell Medicine in New York say they’ve discovered a potential new target for treating osteoporosis—the blood vessels inside of bones. And they have promising results in mice showing a molecule that promotes the growth of those blood vessels reverses the weakening of bones and helps fractures heal.

The molecule is a protein called SLIT3, which is best known for boosting nerve growth, according to a statement from Weill Cornell. The scientists discovered it by examining mice that had abnormally high bone mass as a result of being engineered to lack another protein, called SHN3.

When they studied the osteoblasts from those animals, they found that the cells secreted stable amounts of virtually every substance that’s known to promote the growth of blood vessels in bone. But they also produced unusually high amounts of SLIT3.

"We next asked if we could use SLIT3 to treat mice with skeletal disease, especially osteoporosis and fracture healing," said co-author Matthew Greenblatt, M.D., an assistant professor of pathology and laboratory medicine at Weill Cornell, in the statement.

So they tried it in a mouse model of postmenopausal osteoporosis. It worked, counteracting bone loss the mice had suffered. The researchers published their results in the journal Nature Medicine.

The effort to combat osteoporosis by finding new ways to restore bone-building has been lucrative for some companies. Among them is Amgen, which is expected to bring in $4 billion in sales this year for its bone-strengthening drug Prolia. Earlier this week, Amgen won FDA approval for Prolia’s fifth indication, to treat patients with glucocorticoid-induced osteoporosis.

Still, there have been some setbacks in osteoporosis research. Last year, Amgen and UCB announced that their experimental osteoporosis drug Evenity (romosozumab) reduced fracture risk by 27%, but questions about whether the drug raises the risk of cardiovascular side effects cast doubts on its blockbuster potential.

Greenblatt believes drugs targeting the SLIT3 pathway could hold promise for treating seniors with osteoporosis either on their own or in combination with existing drugs. They could also benefit young people with hard-to-treat bone injuries. "Some of those people’s fractures don’t heal because they can’t grow the right type of blood vessels at the site of the fracture," he explained.

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