The findings of a study published recently in the open access journal, PLoS Medicine, suggest that there is a link between a type of drug introduced in the 1990s to treat type 2 diabetes (thiazolidinediones) and bone fracture.

The study is the work of Ian Douglas of the London School of Hygiene and Tropical Medicine and colleagues. They reviewed the UK General Practice Research Database which is a computerized record of clinical records from over six million patients registered at 400 general practice surgeries in the United Kingdom.

The authors categorized 1,819 individuals aged 40 years or older who had a recorded bone fracture and who had been prescribed a thiazolidinedione at least once. They conducted a self-controlled case-series study. They evaluated how often an event, such as bone fracture, occurs in a population of people during the time when they are taking a particular medication which is in this case a thiazolidinedione drug. They then compared it against the period when those individuals are not taking the medication. They considered the age factor since with age the risk of bone fracture is higher. Findings indicated in the group of people identified that there were nearly one and half times as many fractures when people were taking thiazolidinediones than when they were not taking these drugs.

In both men and women, the increased risk of fracture was observed. In addition, it applied to a broad range of fracture sites on the body. The findings also indicated that the risk of fracture increased as the duration of treatment with the drug increased.

The major benefit of the study design is that it eliminates the likelihood that differences between people who do and do not get prescribed a drug alter the results. The researchers recognize that like any study, there could be additional sources of predisposition because it is observational and not a randomized trial. However, the findings are in accordance with the conclusions of recent trials that suggested an association between thiazolidinediones and bone fracture.

The researchers write in conclusion that the results “should be taken into consideration in the wider debate surrounding the possible risks and benefits of treatment with thiazolidinediones.”

This work was funded by a grant from the Wellcome Trust obtained by Professor Smeeth. The Wellcome Trust played no part in the design and conduct of the study; collection, management, analysis and interpretation of the data; and preparation, review or approval of the manuscript.

“The Risk of Fractures Associated with Thiazolidinediones: A Self-controlled Case-Series Study”
Douglas IJ, Evans SJ, Pocock S, Smeeth L (2009)
PLoSMed 6(9): e1000154.
doi:10.1371/journal.pmed.1000154
PLoS Medicine

Written by Stephanie Brunner (B.A.)