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J Appl Physiol 102: 1502-1509, 2007. First published December 21, 2006; doi:10.1152/japplphysiol.00815.2006
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Doping dose of salbutamol and exercise: deleterious effect on cancellous and cortical bones in adult rats

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

1Caracterisation du Tissu Osseux par Imagerie, Techniques et Applications and Architecture du Tissu Osseux-Exercise Physiology, Institut National de la Santé et de la Recherche Médicale U658, School of Sports Sciences and Physical Education, Orleans Regional Hospital and University of Orleans, Orleans, and 2Laboratoire de Biologie du Tissu Osseux, Institut National de la Santé et de la Recherche Médicale E366, University of St. Etienne, France

Submitted 25 July 2006 ; accepted in final form 18 December 2006

Animal studies suggest that bone remodeling is under beta-adrenergic control via the sympathetic nervous system. To our knowledge, the impact of beta-agonist substances, at doping doses, has not been studied in adult rats. The purpose of this study was to examine the effects of salbutamol injections with or without treadmill exercise on trabecular and cortical bone in adult rats. Adult (36 wk of age) female Wistar rats (n = 56) were treated with salbutamol (3 mg·kg–1·day–1 sc, 5 days/wk) or vehicle (sham) with or without subsequent treadmill exercise (13 m/min, 60 min/day, 5 days/wk) for 10 wk. Tibial and femoral bone mineral density was analyzed by dual-energy X-ray absorptiometry. Metaphysic trabecular bone structure was analyzed by micro-CT at the time of the animals' death. Bone cell activities were assessed histomorphometrically. After 10 wk, the increase in bone mineral density was less in salbutamol-treated than in sham rats (+3.3% vs. +12.4%, P < 0.05), and trabecular parameters were altered and bone resorption was increased in salbutamol-treated rats compared with controls. The negative effect on bone architecture in salbutamol-treated rats persisted, even with treadmill exercise. These results confirm the deleterious effect of beta2-agonists on bone mass during chronic treatment and describe its effects on bone mechanical properties in adult rats. Bone loss occurred independently of a salbutamol-induced anabolic effect on muscle mass and was equally severe in sedentary and exercising rats, despite a beneficial effect of exercise on the extrinsic and intrinsic energy to ultimate strain. These bone effects may have important consequences in athletes who use salbutamol as a doping substance.

beta-agonist; architecture; histomorphometry; doping



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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N. Bonnet, N. Laroche, H. Beaupied, L. Vico, E. Dolleans, C. L. Benhamou, and D. Courteix
Doping dose of salbutamol and exercise training: impact on the skeleton of ovariectomized rats
J Appl Physiol, August 1, 2007; 103(2): 524 - 533.
[Abstract] [Full Text] [PDF]




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