The maker of the drug, GlaxoSmithKline (GSK), disputes the osteoporosis finding. The company said in a statement today that their ADOPT studies showed no increase in spine or hip fractures which are associated with osteoporosis.

The company says they will be looking further into the subject.There are other possibly safer alternative treatments for diabetes, according to Paul Brandt, an associate professor of neuroscience and experimental therapeutics at Texas A&M Health Science Center College of Medicine. “Anyone who is already at risk for osteoporotic fractures should consider an alternative anti-diabetic drug.”

Amanda Gardner of HealthDay News reports that Avandia affects a key cellular protein called the peroxisome proliferator-activated receptor (PPAR-gamma). The mice studies by the Salk Institute for Biological Studies in La Jolla California found that activating this receptor stimulates the production of osteoclasts. These osteoclasts degrade bone.

Avandia recently received some bad press concerning the relation of the drug with heart problems. Avandia, along with four other drugs in the same class, were given blackbox warnings by the Food and Drug Administration (FDA). These warnings are the strictest advisories offered by the FDA for products that they have approved. The drug was linked to heart failure in some patients.

SOURCE: Avandia Recall › Type 2 diabetes drug Avandia linked to osteoporosis and bone loss

Compared with other diabetes pills, Avandia’s use was associated with a 60 percent higher risk of heart failure, 40 percent higher risk of heart attack and 30 percent higher risk of death in patients 65 and older, the researchers found.

“The risks associated with these drugs may outweigh the benefits, at least for older populations,” said Dr. Lorraine L. Lipscombe, the lead author of the study and a researcher at a health research agency funded by the Ontario government.

The findings, published in the influential Journal of the American Medical Association, will probably intensify pressure on the government to restrict sales of the oral diabetes medicine.

“It should come off the market,” said Dr. Sidney M. Wolfe, director of health research at Public Citizen, a liberal interest group preparing to petition the Food and Drug Administration to pull the drug.

Sales of Avandia have plummeted since Dr. Steven Nissen, a prominent cardiologist, reported in May that it raised the risk of heart attack. His report prompted congressional hearings and demands to stop sales.

The FDA decided against that last month, instead adding a label warning that urges users to consult a doctor if they have serious heart problems.

The decision divided agency staff. Ultimately, FDA officials decided the scientific evidence wasn’t conclusive, and they asked Avandia’s manufacturer to conduct a long-term study.

In a statement, the FDA said it would review the results from the Canadian study, but it needs more evidence before taking any further action. “This new study we have just seen today does not change FDA’s recommendations,” the agency said.

GlaxoSmithKline, Avandia’s maker, dismissed the Canadians’ findings as limited and misleading because the elderly studied might have been at higher risk of heart problems.

The Philadelphia company, which is conducting a long-term study of Avandia’s side effects, said in a statement that many other studies show Avandia is safe and effective.

The new study is the first to review side effects in real patients, rather than test subjects, according to Lipscombe, a researcher at the Institute for Clinical Evaluative Sciences in Toronto.

Beginning in March, Lipscombe and her colleagues analyzed health care records for all elderly Ontario residents who took an oral diabetes medicine between 2002 and 2006.

Lipscombe said they focused on the elderly because 40 percent of diabetes patients in Ontario are 65 and older, but the elderly tend to be underrepresented in scientific drug studies.

The researchers didn’t find a higher heart risk among users of Actos, an Avandia competitor that belongs to the same class of diabetes drugs, but Lipscombe said there weren’t enough Actos users to draw a firm conclusion.

December 12th, 2007 by Jonathan D. Rockoff with baltimoresun.com

SOURCE: Avandia Recall › Avandia risks highlighted

Experts fear that, over the long term, Avandia (rosiglitazone) may speed osteoporosis, the thinning of the bones that can lead to dangerous and even fatal fractures.

The findings appear in the Dec. 2 online issue of Nature Medicine.
“Our study suggests that long-term rosiglitazone usage in the treatment of type II diabetes may cause osteoporosis due to both increased bone resorption and decreased bone formation,” said study senior author Ron Evans, a professor at the Salk Institute for Biological Studies in La Jolla, Calif. “Because Avandia is effective in controlling glucose and restoring the body’s sensitivity to insulin, we do not recommend that people stop their treatment. You must balance the benefits against the complications.”

“Anyone who is already at risk for osteoporotic fractures should consider an alternative anti-diabetic drug,” added Paul Brandt, an associate professor of neuroscience and experimental therapeutics at Texas A&M Health Science Center College of Medicine, in College Station. “There are many alternatives, ” he said.

“It may [also] be possible to blunt some of Avandia’s effects with anti-osteoporosis drugs such as bisphosphonates, raloxifene, vitamin D and calcium,” Brandt added.

Earlier this year, Avandia and four other diabetes drugs from the same class were given a “black box” warning by the U.S. Food and Drug Administration. That warning advises users of an increased risk of heart failure while on the drug.

The black box message is the FDA’s strongest label warning.

With an estimated 3.5 million or more U.S. patients taking Avandia, the public health impact from the point of view of both heart failure and bone degradation could be substantial, experts say.

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.”

December 2nd, 2007 by Amanda Gardner with U.S. News

SOURCE: Avandia Recall › Diabetes drug Avandia could weaken bones

The moves by Prime Therapeutics and HealthTrans mark the latest example of U.S. healthcare providers deciding to limit access to the drug, following an earlier decision by the U.S. Department of Veterans Affairs to severely restrict use.

Such actions, particularly if followed by others, may further undermine sales of the once-popular medicine, which have been hit hard recently by a report linking it to heart attacks.

Prime and HealthTrans said in separate statements they had made their decisions after a thorough analysis of the clinical literature examining the safety and efficacy of Avandia.

“Prime takes drug safety warnings very seriously and our primary concern is the safety of our members,” said Craig Mattson, senior director of drug technology assessment and formulary development.

Britain-based Glaxo, Europe’s biggest drugmaker, said it was surprised and disappointed.

“It limits options for treatment and could be detrimental for patients. The FDA (Food and Drug Administration) has said the data remains inconclusive and therefore to limit patients’ options in this is disappointing,” a spokeswoman said.

Concerns about the safety of Avandia were triggered in May by a U.S. analysis linking it to a 43 percent higher risk of heart attack. Avandia was Glaxo’s second-biggest drug in 2006, with worldwide revenue of 1.6 billion pounds ($3.2 billion), but sales have plunged since May, with revenue in the United States down 48 percent in the third quarter from the year-ago period.

SOURCE: Avandia Recall › Two U.S. healthcare providers drop Glaxo’s Avandia

The reason is that while short term studies have linked Avandia to an increased heart attack risk, longer term studies have been inconclusive.

In the meantime, experts suggest that people with heart disease take something other than Avandia.

November 15th, 2007 by Staff with Health News

SOURCE: Avandia Recall › Confusing new warning label on Avandia