Bone fractures, Actos and bladder cancer in women

Actos is an equal opportunity Type 2 diabetes drug that causes bladder cancer in men and women. While both sexes are at risk, men are more at risk.

However, women who take Actos for type 2 diabetes not only are at risk for bladder cancer but are also at risk for fractures known as secondary osteoporosis.

What is worse? Women, what’s worse diabetes or the cure? Type 2 diabetes is manageable with a complementary prescription drug and nutrition. But bladder cancer and bone fractures?

At the School of Medicine, Health Policy and Practice, University of East Anglia in Norwich, UK, their study aimed to determine the risk of fractures associated with thiazolidinedione therapy and to evaluate the effect on bone density. Pioglitazone (Actos) and Rosiglitazone (Avandia) are in the thiazolidinedione (TZD) class of drugs.

For the purpose of the blog post, let’s focus on Actos.

The study analyzed data from 10 randomized controlled trials involving 13,715 participants and from two observational studies involving 31,679 participants. In the thiazolidinedione class of drugs there was a significant increased risk of fractures overall in the 10 randomized controlled trials Five randomized controlled trials showed a significantly increased risk of fractures among women. Bone mineral density in women exposed to thiazolidinediones was significantly reduced at the lumbar spine and hip in two randomized controlled trials.

Interpretation: Long-term thiazolidinedione use doubles the risk of fractures among women with type 2 diabetes, without a significant increase in risk of fractures among men with type 2 diabetes.

In animal models, TZDs induce bone loss by affecting the bone remodeling process; TZDs suppress new bone formation by osteoblasts and increase bone resorption by osteoclasts.

In yet another study, there was evidence that both the TZD class of drugs causes bone loss and increase fracture risk, specifically in women. Observational studies using data from the Health, Aging, and Body Composition cohort reported that older postmenopausal TZD users experience bone loss at the rate of -0.61% annually compared with non-TZD users.

TZD-induced bone loss includes unbalanced bone remodeling processes resulting from decreased bone formation and increased bone resorption. Human and animal studies suggest that aging and estrogen deficiency confound TZD-induced bone loss. Improvement of bone safety of TZD-based therapy may be achieved by using combination therapy with other anti-diabetic therapies, or preventing bone loss by using available anti-osteoporotic drugs, or development of a new class of selective TZDs, which may have sparing or even beneficial effects on skeleton.

Women beware of Actos, bladder cancer, and bone fractures.

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