Animal studies suggest that bone remodeling is under ␤-adrenergic control via the sympathetic nervous system. The purpose of this study was to examine the preventive effect of different doses of nonspecific ␤-blockers (propranolol) on trabecular and cortical bone envelopes in ovariectomized rats. Six-month-old female Wistar rats were ovariectomized (OVX, n ϭ 60) or shamoperated (n ϭ 15). Then, OVX rats were subcutaneously injected with 0.1 (n ϭ 15), 5 (n ϭ 15), or 20 (n ϭ 15) mg/kg propranolol or vehicle (n ϭ 15) for 10 weeks. Tibial and femoral bone mineral density (BMD) were analyzed longitudinally by dual-energy X-ray absorptiometry. At death, the left tibial metaphysis and L 4 vertebrae were removed, and microcomputed tomography (Skyscan 1072; Skyscan, Aartselaar, Belgium) was performed for trabecular bone structure investigation. Histomorphometry analysis was performed on the right proximal tibia to assess bone cell activities. After 10 weeks, OVX rats had decreased BMD and trabecular parameters and increased bone turnover, as well as cortical porosity compared with the sham group (p Ͻ 0.001). Bone architecture alteration was preserved by 0.1 mg/kg propranolol due to higher trabecular number and thickness (ϩ50.35 and ϩ6.81%, respectively, than OVX; p Ͻ 0.001) and lower cortical pore number (Ϫ52.38% than OVX; p Ͻ 0.001). Animals treated by 0.1 mg/kg propranolol had a lower osteoclast surface and a higher osteoblast activity compared with OVX. Animals treated by 20 mg of propranolol did not significantly differ from OVX rats. Animals treated by 5 mg of propranolol have been partially preserved from the ovariectomy. These results showed a dose effect of ␤-blockers. The lower the dose of propranolol breeding, the better the preventive effect against ovariectomy.

The bone response to physical exercise may be under control of the SNS. Using a running session in rats, we confirmed that exercise improved trabecular and cortical properties. SNS blockade by propranolol did not affect this response on cortical bone but surprisingly inhibited the trabecular response. This suggests that the SNS is involved in the trabecular response to exercise but not in the cortical response.Introduction: Animal studies have suggested that bone remodeling is under ␤−adrenergic control through the sympathetic nervous system (SNS). However, the SNS contribution to bone response under mechanical loading remains unclear. The purpose of this study was to examine the preventive effect of exercise coupled with propranolol on cancellous and cortical bone compartments in ovariectomized rats. Materials and Methods: Six-month-old female Wistar rats were ovariectomized (OVX, n ‫ס‬ 44) or shamoperated (n ‫ס‬ 24). OVX rats received subcutaneous injections of propranolol 0.1 mg/kg/day or vehicle and were submitted or not submitted to treadmill exercise (13 m/minute, 60 minutes/day, 5 days/week) for 10 weeks. Tibial and femoral BMD was analyzed longitudinally by DXA. At death, the left tibial metaphysis and L 4 vertebrae were removed, and CT was performed to study trabecular and cortical bone structure. Histomorphometric analysis was performed on the right proximal tibia. Results: After 10 weeks, BMD and trabecular strength decreased in OVX rats, whereas bone turnover rate and cortical porosity increased compared with the Sham group (p < 0.001). Either propranolol or exercise allowed preservation of bone architecture by increasing trabecular number (+50.35% versus OVX; p < 0.001) and thickness (+16.8% versus OVX; p < 0.001). An additive effect of propranolol and exercise was observed on cortical porosity but not on trabecular microarchitecture or cortical width. Biomechanical properties indicated a higher ultimate force in the OVX-propranolol-exercise group compared with the OVX group (+9.9%; p < 0.05), whereas propranolol and exercise alone did not have any significant effect on bone strength. Conclusions: Our data confirm a contribution of the SNS to the determinants of bone mass and quality and show a antagonistic effect of exercise and a ␤-antagonist on trabecular bone structure.

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 beta(2)-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.