A drug commonly prescribed to diabetes patients may have negative effects on the bone, suggests a paper online in Nature Medicine.
Proper bone strength is maintained by a balance between the activities of the cells that degrade bone -- osteoclasts -- and the cells that build it -- osteoblasts. Rosiglitazone, which is prescribed to people with diabetes to increase their response to insulin, has been associated with increased fracture risk, owing to an inhibitory action on osteoblasts. Ron Evans and colleagues show that, in mice, rosiglitazone also results in the inappropriate maturation of osteoclasts, providing an additional explanation for why thiazolidinediones (the group of drugs including rosiglitazone) can increase fracture risk.
The team found that deletion of the gene encoding the protein PPAR-gamma, the molecular target of rosiglitazone, specifically in the cells that give rise to mature osteoclasts impaired their differentiation, leading to higher bone mass. By contrast, when they used rosiglitazone to activate PPAR-gamma, they saw more osteoclast activity and thinner bones-- osteoporosis.
These results raise the concern that long-term use of rosiglitazone to treat diabetes could lead to osteoporosis.
Ron Evans (The Salk Institute for Biological Studies, La Jolla, CA, USA)
Abstract available online.
(C) Nature Medicine press release.
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