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J Clin Endocrinol Metab. 2017 Mar 1;102(3):914-922. doi: 10.1210/jc.2016-3237.

Pioglitazone and Risk for Bone Fracture: Safety Data From a Randomized Clinical Trial.

Author information

1
Yale School of Medicine, New Haven, Connecticut 06510.
2
National Institute of Neurological Disorders and Stroke, Bethesda, Maryland 20892.
3
Alpert Medical School of Brown University, Providence, Rhode Island 02903.
4
Maine Medical Center, Portland, Maine 04102; and.
5
Division of Neurology, Cook County Health and Hospitals System, Chicago, Illinois 60612.

Abstract

Context:

Pioglitazone reduces cardiovascular risk in nondiabetic patients after an ischemic stroke or transient ischemic attack (TIA) but is associated with increased risk for bone fracture.

Objective:

To characterize fractures associated with pioglitazone by location, mechanism, severity, timing, and sex.

Design, Setting, and Patients:

Patients were 3876 nondiabetic participants in the Insulin Resistance Intervention after Stroke trial randomized to pioglitazone or placebo and followed for a median of 4.8 years. Fractures were identified through quarterly interviews.

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 to 1.89). In each group, ∼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, nonpathological), the risk increment was 1.6% (4.7% vs 3.1%; HR, 1.47; 95% CI, 1.03 to 2.09). Increased risk for any fracture was observed in men (9.4% vs 5.2%; HR, 1.83; 95% CI, 1.36 to 2.48) and women (14.9% vs 11.6%; HR, 1.32; 95% CI, 0.98 to 1.78; interaction P = 0.13).

Conclusions:

Fractures affected 8.8% of placebo-treated patients within 5 years after an ischemic stroke or TIA. Pioglitazone increased the absolute fracture risk by 1.6% to 4.9% and the relative risk by 47% to 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.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT00091949.

PMID:
27935736
PMCID:
PMC5460686
DOI:
10.1210/jc.2016-3237
[Indexed for MEDLINE]
Free PMC Article

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