@article{ref1,
title="Pioglitazone and risk for bone fracture: safety data from a randomized clinical trial",
journal="Journal of clinical endocrinology and metabolism",
year="2016",
author="Viscoli, Catherine M. and Inzucchi, Silvio E. and Young, Lawrence H. and Insogna, Karl L. and Conwit, Robin and Furie, Karen L. and Gorman, Mark and Kelly, Michael A. and Lovejoy, Anne M. and Kernan, Walter N.",
volume="102",
number="3",
pages="914-922",
abstract="CONTEXT: Pioglitazone reduces cardiovascular risk in non-diabetic patients after an ischemic stroke or transient ischemic attack (TIA) but is associated with increased risk for bone fracture. <br><br>OBJECTIVE: To characterize fractures associated with pioglitazone by location, mechanism, severity, timing, and sex. DESIGN, SETTING AND PATIENTS: Patients were 3876 non-diabetic participants in the Insulin Resistance Intervention after Stroke trial randomized to pioglitazone or placebo after an ischemic stroke or TIA and followed for a median of 4.8 years. Fractures were identified through quarterly interviews. <br><br>RESULTS: At 5 years, the increment in fracture risk between pioglitazone and placebo groups was 4.9% (13.6% vs. 8.8%; hazard ratio [HR], 1.53; 95% confidence interval [CI], 1.24-1.89). In each group, approximately 80% of fractures were low-energy (i.e., resulted from fall) and 45% were serious (i.e., required surgery or hospitalization). For serious fractures most likely to be related to pioglitazone (low-energy, non-pathological), the risk increment was 1.6% (4.7% vs. 3.1%; HR, 1.47; 95% CI, 1.03-2.09). Increased risk for any fracture was observed in men (9.4% vs. 5.2%; HR, 1.83; 95% CI, 1.36-2.48) and women (14.9% vs 11.6%; HR, 1.32; 95% CI, 0.98-1.78; interaction p-value = 0.13). No skeletal region was affected more than another. <br><br>CONCLUSIONS: Fractures affected 8.8% of placebo-treated patients within five years after an ischemic stroke or TIA. Pioglitazone increased the absolute fracture risk by 1.6%-4.9% and the relative risk by 47-60%, depending on fracture classification. Our analysis suggests that treatments to improve bone health and prevent falls may help optimize the risk/benefit ratio for pioglitazone.<p /> <p>Language: en</p>",
language="en",
issn="0021-972X",
doi="10.1210/jc.2016-3237",
url="http://dx.doi.org/10.1210/jc.2016-3237"
}