β-1 Adrenergic Agonist Mitigates Unloading-Induced Bone Loss by Maintaining Formation

• Published in: Medicine and science in sports and exercise 2013-09, Vol.45 (9), p.1665-1673
• Main Authors: SWIFT, JOSHUA M., HOGAN, HARRY A., BLOOMFIELD, SUSAN A.
• Format: Article
• Language: English
• Subjects: Absorptiometry, Photon; Adrenergic beta-1 Receptor Agonists - pharmacology; Animals; Biological and medical sciences; Biomechanical Phenomena - physiology; Bone Density - drug effects; Bone Resorption - physiopathology; Bone Resorption - prevention & control; Diseases of the osteoarticular system; Dobutamine - pharmacology; Fundamental and applied biological sciences. Psychology; Hindlimb Suspension; Human physiology applied to population studies and life conditions. Human ecophysiology; Male; Medical sciences; Osteogenesis - drug effects; Osteoporosis. Osteomalacia. Paget disease; Rats; Rats, Sprague-Dawley; Space life sciences; Tibia - diagnostic imaging; Tibia - drug effects; Tibia - physiopathology; Tomography, X-Ray Computed; Vertebrates: body movement. Posture. Locomotion. Flight. Swimming. Physical exercise. Rest. Sports
• ISSN: 0195-9131; 1530-0315
• DOI: 10.1249/MSS.0b013e31828d39bc

INTRODUCTIONRecent 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). METHODSMale 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). RESULTSIn 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. CONCLUSIONIn 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.