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

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

Initially, it was thought that rosiglitazone, the generic term for the drug that is marketed as Avandia, was serving as a governor to the bone-building process. In other words, as bones evolve in the human body (much like skin), it was originally thought that Avandia somehow contributed towards an inability to effectively regenerate bone lost in the natural regenerative process.

However, this latest conclusion-arrived at quite by accident-reveals that rosiglitazone actually contributes to bones loss over long treatment periods. Rather then prevent bone from regenerating, Avandia contributes to actual bone loss.

The finding leads to “a better understanding of the challenges associated with long-term treatment of patients with Type II diabetes,” according to Ronald M. Evans of the Salk Institute for Biological Studies in La Jolla, Calif., lead author of the report.

Researchers were conducting studies on diabetic mice, when they stumbled upon their surprising conclusion. Their findings offer hope that this aspect of Avandia as a contributor to bone loss could be further studied and isolated and, one day, ‘dialed-out’ of a future generation of drugs dedicated to the treatment of Type 2 Diabetes.

The Howard Hughes Medical Institute, and the National Institutes of Health funded the research. The findings appeared in this week’s online issue of Nature Medicine.

Researchers found that rosiglitazone-Avandia-stimulates the cells that break down bone in the body, for future regeneration. Osteoporosis occurs when the body loses more bone that it has the capacity to regenerate. Osteoporosis is of particular concern to older women, and this latest research suggests that Avandia should not be prescribed to patients with a history of osteoporosis.

Further, for Avandia patients who also suffer from chronic osteoporosis, there is now the possibility of a contributing cause to the bone loss.

It may not just be from aging. Avandia may be helping it along.

SOURCE: Avandia Recall › Avandia now linked to Osteoporosis

New research raises the possibility that long-term treatment with rosiglitazone, as Avandia is also called, could lead to osteoporosis. The diabetes drug is used to improved response to insulin.

While bones seem solid, they constantly are being broken down and rebuilt by the body. Researchers found that in mice, the drug increased the activity of the cells that degrade bones, according to a report in this week’s online issue of Nature Medicine.

Avandia recently was labeled with warnings about the risk of heart failure in some patients. GlaxoSmithKline, which markets the drug, already has acknowledged that a study found a higher risk of fractures among women who take the drug. But this report is the first to attempt to explain the link between the drug and fractures.

The finding “has led to a better understanding of the challenges associated with long-term treatment of patients with Type II diabetes,” said Ronald M. Evans of the Salk Institute for Biological Studies in La Jolla, Calif., lead author of the report.

“It also provides a basis for the development of a ‘next generation’ of drug that can specifically dial out this side effect and a new insight into a previously unrecognized aspect of bone physiology that has important medical consequences,” he said in an interview via e-mail.

Nearly 21 million people in the United States have diabetes. Rosiglitazone is widely used in people with Type II, or adult onset diabetes, the most common form of the disease.

Evans said the discovery was fortuitous. Researchers were looking at different aspects of the diabetic mice and did not realize they would be able to change the bone-removing activity.

The assumption had been that more brittle bones in diabetics were the result of a reduced bone-building activity, not increased bone removal.

“Considering the widespread use of these drugs and the known action in people it is surprising that such a key observation had been missed,” he said.

“The long-term use of rosiglitazone should be cautious in patients with higher risk of fractures such as older women,” he added. Using it in combination with anti-osteoporosis drugs could be beneficial, he said.

The research was funded by the Howard Hughes Medical Institute and the National Institutes of Health.

December 3rd, 2007 by Randolph E. Schmid with Associated Press

SOURCE: Avandia Recall › Diabetes drug may increase bone thinning