Glitazone Bone-Loss Trigger Found

By Liddle, Rachel

The suspected link between glitazones and bone loss may be due to increased production of bone-destroying osteoclasts, studies in mice have suggested. The findings add to fears that patients taking glitazones for type-2 diabetes could be at increased risk of osteoporosis.

Clinical trials, such as A Diabetes Outcome Progress in Trial, have already shown significant loss in bone density of patients taking glitazones.

A study carried out at the Howard Hughes Medical Institute in California, now offers a potential explanation.

It focused on peroxisome proliferator-activator receptor-gamma (PPAR-gamma), the molecular target that is activated by glitazones.

It is known to block osteoblast differentiation but its effect on osteoclasts is unknown.

Mice were genetically engineered to lack PPAR-gamma in osteoclasts. They went on to develop increased bone mass.

By contrast, when mice were given rosiglitazone, which activates PPAR-gamma, they developed osteoporosis.

The researchers argue that activating PPAR-gamma accelerates osteoclast differentiation and bone resorption.

“These findings have potential clinical implications that long- term rosiglitazone use in treatment of type-2 diabetes and insulin resistance could cause osteoporosis, owing to a combination of decreased bone formation and increased bone resorption,’ the researchers commented.

Findings may also offer a novel therapeutic target for osteoporosis and even rheumatoid arthritis. Selective modulators of PPAR-gamma may be able to boost bone mass in these diseases.

rachel.liddle@haymarket.com

Brittle bone link to diabetes drug

Nature Med 2007; Online First

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Copyright Haymarket Business Publications Ltd. Dec 7, 2007

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