Early Trial Offers Hope Treating Rare ‘Brittle Bone’ Disease

Amy Norton

MONDAY, February 21, 2022 (HealthDay News) — A small preliminary study suggests that an experimental drug may help build bone mass in some adults with a rare brittle bone disease.

The disease is called imperfect osteogenesis. Osteogenesis imperfecta (OI) is present at birth and can leave children with soft bones that deform or break easily, although the severity varies widely.

While experts know the culprit genes involved in osteogenesis imperfecta, a new study points to the mechanism of the disease process: increased activity of a protein called TGF-beta.

And when the researchers injected eight adult patients with a drug that inhibits the protein, five showed an increase in bone density. Brendan Lee, professor of molecular and human genetics at Baylor College of Medicine in Houston.

“You have to be careful,” he said, “because more bone doesn’t necessarily mean better bone.”

But the broader hope is that by understanding the mechanisms of OI, it can develop better treatments, perhaps with benefits beyond the bone, Li said.

“It’s not just a bone disease,” he said. “It’s a connective tissue disease.”

Depending on the severity of the condition, people may also suffer from joint instability, muscle weakness, easily bruised skin, hearing loss, or underdevelopment of the lungs. According to the US National Institutes of Health, osteogenesis imperfecta is rare, occurring in 1 in every 10,000 to 20,000 births worldwide. But the medications for osteoporosis, called bisphosphonates, are the basis for treating children with imperfect osteogenesis.

The drugs can increase bone density in children and help them be more active, says Dr. Kathleen Raggio, a pediatric orthopedic surgeon at the Hospital for Special Surgery in New York.

This means they target the symptom rather than the disease process itself, said Raggio, who researches and treats osteogenesis imperfecta.

She agreed that medications targeting the “pathway” in the OI process can “treat the underlying problem rather than the symptoms.”

A study recently published in the Journal of Clinical Research consists of two parts. First, the researchers analyzed bone samples from a small group of children with and without the brittle bone disease.

It turned out that it was.

The researchers then gave eight adult patients a single infusion of fresolimumab, a laboratory-developed antibody that inhibits TGF-beta. The drug has been studied as a treatment for certain types of cancer, among other conditions.

He and colleagues found that five patients with more moderate OI experienced an increase in bone density three to six months after fresolimumab infusion. In the three remaining patients with more severe disease, bone density remained unchanged or decreased.

Past studies of fresolimumab in other conditions have identified some potential risks, including bleeding and skin tumors.

In this study, the patients had no severe side effects from a single infusion, according to Li’s team.

The study was supported by the Fragile Bones Consortium and a research agreement with Sanofi Genzyme, the manufacturer of fresolimumab.

The company will conduct a more extensive study of adults with osteogenesis imperfecta to further test the drug’s safety and its effect on bones.

If the adult studies turn out to be positive, then the question would be whether the drug could help children with OI, possibly added to bisphosphonates, Raggio said.

For now, she says, parents should know that researchers are working to understand the mechanisms of the disease and translate that into treatments.

“No one is saying that fresolimumab or any single drug will help with a disease as complex as OI,” Li said.

“Rarely in medicine, one size fits all,” Lee said.

More information

The OI Foundation has more information on osteogenesis imperfecta.

SOURCES: Brendan Lee, MD, Professor and Chair of the Department of Molecular and Human Genetics, Baylor College of Medicine, Houston; Kathleen L. Raggio, MD, Pediatric Orthopedic Surgeon, Hospital for Special Surgery, New York; Journal of Clinical Research, February 3, 2022, online