&bgr;-1 Adrenergic Agonist Mitigates Unloading-Induced Bone Loss by Maintaining Formation
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INTRODUCTION: Recent data indicate a direct relationship between the sympathetic nervous system and bone metabolism. The purpose of this study was to evaluate the effects of a beta-1 adrenergic (Adrb1) agonist, dobutamine (DOB), on disuse-induced changes in bone integrity during 28 d of hindlimb unloading (HU). METHODS: Male Sprague-Dawley rats, age 6 months, were assigned to either a normal cage activity (CC) or HU (n = 24/group). Animals were given one daily bolus dose (4 mg·kg body weight a day) of DOB (n = 12) or an equal volume of saline (VEH, n = 12). RESULTS: In vivo peripheral quantitative computed tomography scans revealed a 9% loss in proximal tibia metaphysis (PTM) volumetric bone mineral density (vBMD) over 28 d of disuse. DOB administration during HU significantly attenuated reductions in PTM vBMD and inhibited reductions in mid-diaphysis tibia cross-sectional moment of inertia. A significant decline in PTM bone formation rate in the HU-VEH group (-56% vs CC-VEH) was completely abolished in the HU-DOB group. Significant reductions in strength of the femoral shaft and neck in the HU-VEH group (14% and 15%, respectively) were prevented with DOB treatment. CONCLUSION: In conclusion, DOB administration during HU effectively attenuates significant declines in total vBMD at PTM by mitigating associated decrements in bone formation rate. Positive effects of DOB were observed only in unloaded animals, with no effects observed in normal weight-bearing rats. These data provide evidence for the importance of Adrb1 signaling in maintaining osteoblast function during periods of mechanical unloading.
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SWIFT, J. M., HOGAN, H. A., & BLOOMFIELD, S. A.