Received for publication March 29, 2006.
Revised May 24, 2006.
Accepted for publication May 31, 2006.

Dose effects of propranolol on cancellous and cortical bone in ovariectomized adult rats

Abstract

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 non specific 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 propranolol 0.1mg.kg-1 (n=15), 5mg.kg-1 (n=15), 20mg.kg-1 (n=15) or vehicle (n=15) for 10 weeks. Tibial and femoral BMD were analyzed longitudinally by dual-energy x-ray absorptiometry (DEXA). At death, the left tibial metaphysis and L4 vertebrae were removed and microcomputed tomography (Skyscan 1072) 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, trabecular parameters and increased bone turnover, as well as cortical porosity compared to the Sham group (p < 0.001). Bone architecture alteration was preserved by propranolol 0.1mg.kg-1, due to higher trabecular number and thickness, (respectively +50.35%, +6.81% than OVX p < 0.001), and lower cortical pore number (-52.38% than OVX; p < 0.001). Animals treated by propranolol 0.1mg.kg-1 had a lower osteoclast surface, and a higher osteoblast activity compared to OVX. Animals treated by propranolol 20mg did not significantly differ from OVX rats. Animals treated by propranolol 5mg 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.

Key words: architecture, b blocker, cortical bone, histomorphometry, osteoporosis, trabecular bone