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BEHAVIORAL PHARMACOLOGY

Dose Effects of Propranolol on Cancellous and Cortical Bone in Ovariectomized Adult Rats

Institut National de la Santé et de la Recherche Médicale U658, Caracterisation du Tissu Osseux par Imagerie, Techniques, et Applications, Hopital Regional d'Orléans, Université d'Orléans, Orleans, France (N.B., E.D., C.L.B., D.C.); Institut National de la Santé et de la Recherche Médicale E366, St. Etienne, France; Laboratoire de Biologie du Tissu Osseux, Université Jean Monnet, St. Etienne, France; and IFR62 Laennec, Lyon, France (N.L., L.V.)

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 = 60) or sham-operated (n = 15). Then, OVX rats were subcutaneously injected with 0.1 (n = 15), 5 (n = 15), or 20 (n = 15) mg/kg propranolol or vehicle (n = 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 L₄ 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 < 0.001). Bone architecture alteration was preserved by 0.1 mg/kg propranolol due to higher trabecular number and thickness (+50.35 and +6.81%, respectively, than OVX; p < 0.001) and lower cortical pore number (–52.38% than OVX; p < 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.

Address correspondence to: Dr. Nicolas Bonnet, Institut National de la Santé et de la Recherche Médicale U658, CHR Orleans, 1 rue Porte Madeleine, 45000 Orleans, France. E-mail: nicolas.bonnet15{at}wanadoo.fr