New Diabetes Drugs Bad for Bones
Avandia -- and Probably Actos -- Speeds Up Bone Loss
Dec. 3, 2007 -- The diabetes drug Avandia promotes osteoporosis not only by slowing bone growth but also by speeding up bone loss. Actos, the only other drug in the same class, likely does this as well.
The finding, from mouse experiments by Salk Institute researcher Ronald M. Evans, PhD, and colleagues, helps explain why clinical studies show increased bone fracture risk in people taking Avandia.
Bones stay healthy through an ongoing process called remodeling. The body is constantly breaking down and rebuilding bone. This system of resorption and deposition is tightly controlled with many checks and balances.
"The drug shifts this balance on both sides," Evans tells WebMD. "People taking this drug have somewhat decreased bone deposition -- that is a known action of the drug, resulting in mild bone loss. But what we discovered is it increases bone resorption in a fairly robust way."
Avandia belongs to the glitazone class of drugs, which enhances a chemical signal called PPAR-gamma. One effect of the drug is to increase the body's sensitivity to insulin. But another effect, Evans and colleagues now show, is to activate the bone-eating cells called osteoclasts.
"I would expect to see the same thing with Actos, although we did not actually do that experiment," Evans says. "But it is almost certainly a drug-class effect because the mediator of this effect is the target of both drugs."
Bone Risk From Avandia, Actos
"This is not meant to scare people," Evans asserts. "Only Avandia and Actos act in this unique way, and these drugs are an overall benefit for the patients who take them."
But bone expert J. Edward Puzas, PhD, professor of orthopaedics at the University of Rochester, N.Y., says the new finding confirms something bone researchers have been worrying about.
"This is a nicely done study of how these drugs stimulate the cells that eat away at bone. This leads to lower bone mass and higher bone fragility," Puzas tells WebMD.
Puzas is worried because bone changes occur very slowly, so researchers may only be beginning to appreciate the scope of the problem.
Philip T. Rodgers, PharmD, clinical associate professor of pharmacy at the University of North Carolina, hopes the new findings will make doctors pay more attention to the bone risks posed by Avandia and Actos.
"There is an underappreciation of the risks of osteoporosis with these drugs," Puzas says. "I don't think doctors are paying enough attention to testing the bone-mineral density of people on these drugs."
Mary Anne Rhyne, a spokeswoman for Avandia maker GlaxoSmithKline, says the company is already aware of the drug's bone risks. She notes that the company recently updated the drug's label to reflect new data on fracture risk.
"We have a comprehensive, ongoing clinical program to better understand the mechanism of fractures," Rhyne tells WebMD.
While they worry about the bone risks from Avandia and Actos, both Puzas and Rodgers note that the drugs' benefits outweigh the risks for many patients.
Both suggest that doctors should screen patients for osteoporosis before starting them on Avandia or Actos therapy. And both suggest that patients taking the drugs should discuss bone-protection strategies with their doctors.
Meanwhile, Evans says the new findings should help researchers come up with new diabetes drugs that improve insulin sensitivity without stimulating bone loss.
Evans and colleagues report their findings in this week's advance online issue of Nature Medicine.