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J Appl Physiol 103: 524-533, 2007. First published May 3, 2007; doi:10.1152/japplphysiol.01319.2006
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Doping dose of salbutamol and exercise training: impact on the skeleton of ovariectomized rats

N. Bonnet,1 N. Laroche,2 H. Beaupied,1 L. Vico,2 E. Dolleans,1 C. L. Benhamou,1 and D. Courteix1

1INSERM U658, Caracterisation du Tissu Osseux par Imagerie, Techniques et Applications and Architecture du Tissu Osseux—Exercise Physiology, School of Sports Sciences and Physical Education, Orleans Regional Hospital and University of Orleans, Orleans; and 2INSERM E366, Laboratoire de Biologie du Tissu Osseux, University of St. Etienne, St. Etienne, France

Submitted 21 November 2006 ; accepted in final form 26 April 2007

Previous studies in healthy rats have demonstrated a deleterious bone impact of beta-agonist treatment. The purpose of this study was to examine the trabecular and cortical effects of beta2-agonists at doping dose on treadmill exercising rats with estrogen deficiency. Adult female rats were ovariectomized (OVX; n = 44) or sham operated (n = 12). Then, OVX rats received a subcutaneous injection of salbutamol (SAB) or vehicle with (EXE) or without treadmill exercise for 10 wk. Bone mineral density (BMD) was analyzed by densitometry. Microcomputed tomography and histomorphometric analysis were performed to study trabecular bone structure and bone cell activities. After 10 wk, SAB rats presented a much more marked decrease of BMD and trabecular parameters. Exercise did not change the high level of bone resorption in OVX EXE SAB compared with OVX SAB group (both on COOH-terminal collagen cross-links and osteoclast number). These results confirm the deleterious effect of beta2-agonists on bone quantity (femoral BMD gain: OVX EXE, +6.8%, vs. OVX EXE SAB, –1.8%; P < 0.01) and quality (–8.0% of femoral trabecular thickness in OVX EXE SAB vs. OVX EXE), indicating that SAB suppresses the effect of EXE in OVX rats. Furthermore, we notice that the slight beneficial effect of exercise was mainly localized in the tibia. These findings indicate the presence of a bone alteration threshold below which there is no more alteration in structural bone quantity and quality. The negative effects of SAB on bone observed in this study in trained rats may indicate potential complications in doping female athletes with exercise-induced amenorrhea.

beta-agonist; estrogen deficiency



Address for reprint requests and other correspondence: N. Bonnet, Inserm U658, CHR Orleans, 1, rue porte Madeleine, 45000 Orleans, France (e-mail: nicolas.bonnet15{at}wanadoo.fr)




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