Alteration of trabecular bone under chronic beta2 agonists treatment.
OBJECTIVE
beta2 adrenergic agonists are widely used as doping agents. Their side effects on bone, especially microarchitecture, remain unknown. The purpose of this study was to evaluate the effects of chronic clenbuterol and salbutamol treatment on bones of growing rats.


METHODS
Twelve-week-old Wistar female rats were divided into three groups: salbutamol (4 mg.kg(-1).d(-1)), clenbuterol (2 mg.kg(-1).d(-1)), and normal saline (0.5 mL.kg(-1).d(-1)) and treated for 6 wk. Proximal tibia and lumbar spine L4 were analyzed by absorptiometry and by 3D microcomputed tomography. Bending and compression tests were used to measure their mechanical properties.


RESULTS
After 6 wk, the salbutamol and clenbuterol groups had lower bone mineral density (BMD) in the tibia, proximal tibia, and vertebrae. Trabecular number and bone volume for the vertebrae were lower in animals treated with clenbuterol (Tb.N: -14.31%, P < 0.001; BV/TV: -21.07%, P < 0.001) or salbutamol (TbN: -12.7%, P < 0.001; BV/TV: -19.7%, P < 0.001) than in controls. Mechanical properties of the tibia were affected by clenbuterol with a lower ultimate force (P = 0.02) and a trend in lower energy to ultimate force (P = 0.053). In vertebrae, salbutamol and clenbuterol induced lower ultimate force. Clenbuterol significantly increased muscle mass (+58.83%, P < 0.01) and reduced fat mass (-28.75%, P < 0.01) compared with controls +17.07 and -7.34%, respectively.


CONCLUSIONS
This study shows a negative effect of clenbuterol and salbutamol on the mechanical properties and microarchitecture of trabecular bone. In the clenbuterol group it was notable that the bone loss contrasts with the anabolic effect on muscle mass. Clearly an increase of muscle mass with enhanced bone fragility augments the risk of fractures for humans or animals treated with beta2 agonists as part of a doping regimen.
Bonnet
Nicolas
N
Bone Microarchitecture Tissue and Physical Exercise and Architecture Bone Tissue, School of Sports Sciences and Physical Education, Orleans Regional Hospital and University of Orleans, France. nicolas.bonnet15@wanadoo.fr
Brunet-Imbault
Barbara
B
Arlettaz
Alexandre
A
Horcajada
Marie N
MN
Collomp
Katia
K
Benhamou
Claude L
CL
Courteix
Daniel
D
D000273:Adipose Tissue / Q000187:drug effects; D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000420:Albuterol / Q000494:pharmacology*; D000818:Animals; D001696:Biomechanical Phenomena; D001835:Body Weight / Q000187:drug effects; D015519:Bone Density / Q000187:drug effects; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D002976:Clenbuterol / Q000494:pharmacology*; D004195:Disease Models, Animal; D004300:Doping in Sports / Q000379:methods*; D004305:Dose-Response Relationship, Drug; D005260:Female; D008159:Lumbar Vertebrae / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D018482:Muscle, Skeletal / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D013977:Tibia / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure
D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists; D000420:Albuterol; D002976:Clenbuterol