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Researchers probe insulin growth factor, proteins for osteoporosis treatment
Elevated IGF-1 levels in animal models led to augmented bone and muscle mass.
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TORONTO — Scientists are giving greater consideration to the potential some biologic units — such as the protein Wnt and insulin growth factor-1 — may have as therapies for osteoporosis.
Speaking at the International Osteoporosis Foundation World Congress on Osteoporosis, Roland Baron, PhD, professor of orthopaedics and cell biology at Yale University School of Medicine, said he and his colleagues are studying how cell manipulation can lead to new treatment pathways.
“We have to recognize the need to develop new ways of treatment that will increase bone mass, rather than just prevent bone loss,” he said.
Baron said genetic studies would likely provide clues to developing new drugs and identifying new therapeutic pathways. “We want to identify more families that have high bone mass and those that have low bone mass and start making comparisons between the two groups” to identify potential causing genes.
Genetic missteps
He said the “signaling” of the Wnt/beta-catenin pathway clearly plays an important role in the maintenance of strong bones.
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Likewise, the loss of function of the low-density lipoprotein receptor-related protein-5 (LRP5), a co-receptor for Wnt, could lead to osteoporosis. A specific mutation in the receptor leads to high bone mass, whereas a loss of function leads to early onset osteoporosis in osteoporosispseudoglioma syndrome, Baron said. Because LRP5 functions as a co-receptor for Wnt proteins, investigators are focused on the signaling of Wnt and its purported significant role in bone biology.
In animal models, lithium has been shown to enhance bone formation and augment bone mass in mice. “It is thought that lithium does this via activation of the Wnt pathway,” he said.
Insulin growth factor-1
Endocrinologist Clifford Rosen, MD, said physicians should also consider the role insulin growth factor-1 (IGF-1) plays in bone health.
There are a few clinical trials focusing on circulating IGF-1 and its effect on bone resorption, Rosen said, but researchers have found that elevated IGF-1 levels in animal models can lead to augmented bone mass and muscle mass.
Still, “We know very little about the regulation of IGF-1 at the molecular level,” said Rosen, who is the director of the Maine Center for Osteoporosis and Education in Bar Harbor, U.S.A.
“But we know that studying IGF-1 will lead to greater understanding of cell metabolism, cell cycle proliferation and fuel conservation,” he said. “This is starting to emerge as a major story for bone.”
For more information:
- Baron R. Wnt as a target for therapy.
- Rosen C. IGF and bone health. Both presented at the IOF World Congress on Osteoporosis. June 2-6, 2006. Toronto.