Avandia affects a key cellular protein called the peroxisome proliferator-activated receptor (PPAR-gamma). In their study, the California team discovered that, in mice, activating this receptor also stimulates the production of osteoclasts, cells whose key function is to degrade bone.
Proper bone health is maintained by a balance between osteoclasts and osteoblasts, the cells that build bone up.
If either side is out of whack, so to speak, bones become thinner, more fragile and prone to fracture.
The current results are particularly disturbing in light of prior studies, the experts said.
"It was previously known that Avandia mediates bone loss by inhibiting bone formation," Evans explained. "Our work identified an additional mechanism, in which Avandia promotes bone resorption. These are the two parts of the checks-and-balance system that maintains bone in good shape. The drug weakens both sides of the balance mechanism, leading to an increased risk for osteoporosis."
"Previous research showed that Avandia reduced osteoblasts," Brandt added. "Combine the two, and you're going to get thinning of the bone."
For more on diabetes drugs, visit the U.S. Food and Drug Administration.
SOURCES: Ron Evans, Ph.D., professor, The Salk Institute for Biological Studies, and investigator, Howard Hughes Medical Institute, March of Dimes Chairman, Molecular and Developmental Biology, La Jolla, Calif.; Paul Brandt, Ph.D., associate professor, neuroscience and experimental therapeutics, Texas A&M Health Science Center College of Medicine, College Station; Dec. 2, 2007, Nature Medicine online
All rights reserved