December 3, 2007

Avandia Causes Osteoporosis and Broken Bones--But Actos Does TOO!

This week's medical news is full of reports about a study that explains why Avandia causes osteoporosis.

Here's a report that gives more than the usual amount of detail about this study:

Avandia Researchers Find Reason Behind Bone Fracture, Osteoporosis Side Effects

I have already blogged about Avandia's connection with a doubling of the incidence of fractures this last year HERE.

But what concerns me now is that the way this new story is being reported makes it sound as if the osteoporosis is only a side effect of Avandia, a drug that for all practical purposes is dead after the press discovered the long-known fact that research proved it increases heart attacks.

But as the article I link above makes clear, the reason Avandia causes the bones to thin is because of the way it affects the PPAR-gamma receptor. To quote the report cited above, "the new research found that Avandia also appears to affect a key cellular protein called the peroxisome proliferator-activated receptor (PPAR-gamma). In their study, the California team discovered that activating this receptor in mice also stimulates the production of osteoclasts, cells whose key function is to degrade bone."

Those of you who study diabetes drugs know that it is NOT news that both Avandia and Actos stimulate PPAR-gamma. In fact, this PPAR-gamma stimulation has been the mechanism used to explain how these drugs work ever since the drug companies started selling them over a decade ago. So this finding that Avandia's effect on PPAR-gamma destroys bone suggests strongly that Actos, too, may cause osteoporosis and fractures.

The way the media has spun the Avandia story until now has been that Avandia is bad but Actos, its competitor, is still a good choice. But this new finding should make us think twice about using Actos at all.

The prescribing information for Actos clearly cites that osteoporosis and a doubling of bone fractures has been found by research to be an Actos side effect.

Here is what the FDA-mandated Prescribing Information for ACTOS tells us:

Fractures: In a randomized trial (PROactive) in patients with type 2 diabetes (mean duration of diabetes 9.5 years), an increased incidence of bone fracture was noted in female patients taking pioglitazone. During a mean follow-up of 34.5 months, the incidence of bone fracture in females was 5.1% (44/870) for pioglitazone versus 2.5% (23/905) for placebo. This difference was noted after the first year of treatment and remained during the course of the study. The majority of fractures observed in female patients were nonvertebral fractures including lower limb and distal upper limb. No increase in fracture rates was observed in men treated with pioglitazone 1.7% (30/1735) versus placebo 2.1% (37/1728). The risk of fracture should be considered in the care of patients, especially female patients, treated with pioglitazone and attention should be given to assessing and maintaining bone health according to current standards of care.

Note that these studies only lasted a few years. Over time it is likely that a higher incidence of broken bones and osteoporosis would be found with this drug. Men have thicker bones than women and it would take longer for bone thinning in males to be diagnosed.

Bottom line: Broken hips are one of the biggest killers of older people whose bones naturally thin with age. Hastening the degeneration of your bones is suicide. Don't take either Avandia or Actos. These drugs do not provide anywhere near enough benefit to outweigh their dangerous side effects.


Anonymous said...

Have you seen Avandia and/or Actos to cause bone lesions?

sharma k said...

I took avandia 4mg once a day for 23 months ended up with fracture of hand then after 6 months other fracture of ankle.then i took 4mg two times a day and ended up with compression fracture of lumbar vertebra.then undergo bone density test in spine institute and was diagnosed as osteoporosis and doctor put me on alendron ate vit- d and calcium for one year