October 1, 2015

Avandia Ups Bone Fracture Risk

Avandia is back in the news, and not in a good way. Inside our bones there is fat. Diabetes increases the amount of this marrow fat. A study from the UNC School of Medicine shows how some diabetes drugs substantially increase bone fat and thus the risk of bone fractures.

The study, published in the journal Endocrinology, also shows that exercise can decrease the volume of bone fat caused by high doses of the diabetes drug rosiglitazone, which is sold under the brand name Avandia.

These drugs aren’t first or second-line choices of treatment for type-2 diabetes, but some patients do take them,” said study first author Maya Styner, MD, assistant professor of medicine. “And we know there are drugs in development that target the same cellular pathways as rosiglitazone does. We think doctors and patients need to better understand the relationship between diabetes, certain drugs, and the often dramatic effect on bone health.”

According to Styner’s study, Avandia affects bone fat by enhancing a critical transcription factor called PPAR – peroxisome proliferator-activated receptor – which regulates the expression of specific genes in the nuclei of cells. Essentially, rosiglitazone takes glucose out of blood to lower blood sugar and treat diabetes. But that glucose is then packaged into lipid droplets – fat. Other researchers showed that some of that fat is stored in tissue, such as belly fat. Styner’s latest research showed that the drug also causes fat to be stored inside bone.”

The author did state the researchers were surprised at the large amount of bone fat caused by Avandia. They also were somewhat surprised that exercise could reduce this fat. But, that should be expected in a rodent study.

Many patients have been surprised that some diabetes drugs adversely affect bone health. However, diabetes by itself can harm bones.

Yet, other drugs under development that could be close to FDA-approval lower blood sugar by enhancing the PPAR pathway. These drugs are referred to as fibroblast growth factor-21 agonists. “Early reports show that the same bone concerns are popping up with these new drugs,” Styner said. “Doctors and patients need to be aware of this.” Bone fat, in general, isn’t nearly as well understood as other fat depots.”

Our field is just beginning to investigate bone fat and its implications for patients,” Styner said. But she said that more bone fat means less actual bone, which increases the risk of bone fractures.

Styner said her findings are not yet directly relatable to human activity. For humans, running isn’t nearly as natural. But she said she would still advise patients at risk of declining bone health to find an exercise that suits them; the default would be taking very long walks.

Then in an article in Endocrinology Advisor, the FDA is adding a warning to canagliflozin, the SGLT2-inhibitor that this drug increases the risk of bone fracture. Apparently, bone fractures are another source of concern for some of the oral diabetes drugs.

This is why I will stay with insulin and avoid oral medications.

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