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Open Access Highly Accessed Research article

The peroxisome proliferator-activated receptor (PPAR) alpha agonist fenofibrate maintains bone mass, while the PPAR gamma agonist pioglitazone exaggerates bone loss, in ovariectomized rats

Astrid K Stunes1*, Irene Westbroek2, Björn I Gustafsson13, Reidar Fossmark3, Jan H Waarsing2, Erik F Eriksen4, Christiane Petzold5, Janne E Reseland5 and Unni Syversen16

Author Affiliations

1 Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, NTNU, Trondheim, Norway

2 Internal Medicine and Orthopaedics, Erasmus MC, Rotterdam, the Netherlands

3 Department of Gastroenterology, St Olav's University Hospital HF, Trondheim, Norway

4 Hormone Laboratory, Aker University Hospital, Oslo, Norway

5 Department of Biomaterials, Institute for Clinical Dentistry, University of Oslo, Oslo, Norway

6 Department of Endocrinology, St Olav's University Hospital HF, Trondheim, Norway

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BMC Endocrine Disorders 2011, 11:11  doi:10.1186/1472-6823-11-11

Published: 26 May 2011

Abstract

Background

Activation of peroxisome proliferator-activated receptor (PPAR)gamma is associated with bone loss and increased fracture risk, while PPARalpha activation seems to have positive skeletal effects. To further explore these effects we have examined the effect of the PPARalpha agonists fenofibrate and Wyeth 14643, and the PPARgamma agonist pioglitazone, on bone mineral density (BMD), bone architecture and biomechanical strength in ovariectomized rats.

Methods

Fifty-five female Sprague-Dawley rats were assigned to five groups. One group was sham-operated and given vehicle (methylcellulose), the other groups were ovariectomized and given vehicle, fenofibrate, Wyeth 14643 and pioglitazone, respectively, daily for four months. Whole body and femoral BMD were measured by dual X-ray absorptiometry (DXA), and biomechanical testing of femurs, and micro-computed tomography (microCT) of the femoral shaft and head, were performed.

Results

Whole body and femoral BMD were significantly higher in sham controls and ovariectomized animals given fenofibrate, compared to ovariectomized controls. Ovariectomized rats given Wyeth 14643, maintained whole body BMD at sham levels, while rats on pioglitazone had lower whole body and femoral BMD, impaired bone quality and less mechanical strength compared to sham and ovariectomized controls. In contrast, cortical volume, trabecular bone volume and thickness, and endocortical volume were maintained at sham levels in rats given fenofibrate.

Conclusions

The PPARalpha agonist fenofibrate, and to a lesser extent the PPARaplha agonist Wyeth 14643, maintained BMD and bone architecture at sham levels, while the PPARgamma agonist pioglitazone exaggerated bone loss and negatively affected bone architecture, in ovariectomized rats.