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Updated: Aug 16, 2026
Trabecular Bone Microarchitecture Evaluation in an Osteoporosis Mouse Model
Published on: September 8, 2023
Severe bone alterations under beta2 agonist treatments: bone mass, microarchitecture and strength analyses in female
N Bonnet1, C L Benhamou, B Brunet-Imbault
1Inserm U 658, CTI and ATOSEP, Orleans Regional Hospital and University of Orleans, 1, rue porte Madeleine, France. nicolas.bonnet15@wanadoo.fr
Aims:
Beta2 adrenergic agonists are widely used in therapeutics and as doping agents by athletes. However, their effects on bone tissue, especially bone microarchitecture, remain poorly understood. Using three-dimensional (3D) microtomography, dual-energy X-ray absorptiometry, biomechanical testing and enzyme-linked immunosorbent assay, we evaluated the effects of two beta2 agonists, clenbuterol and salbutamol, on bone in growing rats.
Methods:
Twelve-week-old Wistar female rats (N = 39), divided in 3 groups, received during 6 weeks either salbutamol (4 mg/kg/day), clenbuterol (2 mg/kg/day) or normal saline (0.5 ml/kg/day) by subcutaneous injections.
Results:
After 6 weeks, the salbutamol and clenbuterol groups displayed lower bone mineral content (BMC), femoral length and cortical width than controls. Clenbuterol treatment further reduced bone mineral density. Bone microarchitecture was clearly altered by clenbuterol, as evidenced by lower trabecular number (-40.40%; P < 0.001), connectivity and trabecular bone volume (-42.85%; P < 0.001), leading to lower ultimate force. Clenbuterol significantly increased muscle mass (P < 0.01) and reduced fat mass when compared to controls. Salbutamol did not seem to have any effect on bone microarchitecture or body composition. Both beta2 agonists increased the bone resorption marker (C-terminal collagen crosslinks) without any change of a bone formation marker. At the end of the treatment, a drop in leptin was seen in the clenbuterol group only. Leptin levels were correlated with BMC (r = 0.69, P = 0.003).
Conclusion:
These results confirm the deleterious effect of beta2 agonists on bone mass and show the negative effects of clenbuterol on trabecular bone microarchitecture. Bone loss occurred independently from muscle mass but was related to fat mass. A leptin-mediated effect on bone tissue seems likely. These pathophysiological effects may have important consequences in human therapeutics and doping.
Insights
Beta2 agonists like clenbuterol negatively impact bone microarchitecture and mass in rats. Clenbuterol, but not salbutamol, caused significant bone loss and altered body composition, suggesting potential risks in therapeutics and doping.
Area of Science:
- Bone Biology
- Pharmacology
- Endocrinology
Background:
- Beta2 adrenergic agonists are utilized in medicine and as performance-enhancing substances by athletes.
- The impact of these agonists on bone tissue, particularly microarchitecture, is not well-understood.
Purpose of the Study:
- To investigate the effects of clenbuterol and salbutamol on bone tissue in growing rats.
- To assess changes in bone microarchitecture, bone mineral content, and body composition.
Main Methods:
- Growing female rats received subcutaneous injections of salbutamol (4 mg/kg/day), clenbuterol (2 mg/kg/day), or saline for 6 weeks.
- Evaluations included 3D microtomography, DXA, biomechanical testing, and ELISA for bone markers and leptin.
Main Results:
- Clenbuterol and salbutamol reduced bone mineral content, femoral length, and cortical width.
- Clenbuterol significantly worsened bone microarchitecture, decreasing trabecular bone volume and number, and lowering ultimate force.
- Clenbuterol increased muscle mass, reduced fat mass, and decreased leptin levels, which correlated with bone mineral content.
Conclusions:
- Beta2 agonists have detrimental effects on bone mass, with clenbuterol negatively impacting trabecular bone microarchitecture.
- Bone loss was independent of muscle mass but related to fat mass, with a potential leptin-mediated mechanism.
- Findings highlight potential risks associated with beta2 agonist use in human therapeutics and doping.
