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

Related Articles

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

J Clin Endocrinol Metab. 2016 Dec 09;:jc20163237

Authors: Viscoli CM, Inzucchi SE, Young LH, Insogna KL, Conwit R, Furie KL, Gorman M, Kelly MA, Lovejoy AM, Kernan WN, IRIS Trial Investigators

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.
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.
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.
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.

PMID: 27935736 [PubMed - as supplied by publisher]

http://ift.tt/2hj94yg