Aminohydroxybutane bisphosphonate and clenbuterol prevent bone changes and retard muscle atrophy respectively in tail-suspended rats.
Hind-limb unloading by tail suspension of rats, an established model of simulated microgravity, was used to examine the efficacy of aminohydroxybutane bisphosphonate (AHBuBP) and clenbuterol in preventing bone loss and muscle atrophy, respectively. Male Sprague-Dawley rats (299-372 g) were randomized into six groups of six: 1) unsuspended, saline, 2) unsuspended, saline, pair fed with group 3, 3) suspended, saline, 4) suspended, 0.03 mg/kg/day x 2 of AHBuBP, 5) suspended, 0.3 mg/kg/day x 2 of AHBuBP and 6) suspended, 0.3 mg/kg/day x 2 of AHBuBP + clenbuterol (0.5 mg/kg/day i.p. x 6, then 1 mg/kg/day i.p. x 6). Animals in groups 3 to 6 were tail suspended for 14 days from a system of double pulleys and allowed free mobility with their hind limbs unloaded. On days -2 and -1, before suspension on day 0, all rats received a single s.c. injection of either 2 ml/kg of normal saline (vehicle) or AHBuBP. All rats were tested for exercise tolerance before day -2 and on day 10, and grip strength before day -2 and on day 13. On day 14, the rats were euthanized and their humeri, tibias and femurs analyzed in vitro for bone density (by single-photon absorptiometry), strength and stiffness (by 3-point bending). Muscles were analyzed for weight, protein concentration and enzyme activity. Pair feeding had no effect other than on food consumption and body weight. AHBuBP caused a dose-dependent increase in bone density in humeri, tibias and femurs, even in tail-suspended rats, relative to control unsuspended animals, with no significant difference in bone strength or stiffness between AHBuBP groups and unsuspended animals.(ABSTRACT TRUNCATED AT 250 WORDS)
Apseloff
G
G
Department of Pharmacology, College of Medicine, Ohio State University, Columbus.
Girten
B
B
Walker
M
M
Shepard
D R
DR
Krecic
M E
ME
Stern
L S
LS
Gerber
N
N
D019386:Alendronate; D000818:Animals; D015519:Bone Density / Q000187:drug effects; D001842:Bone and Bones / Q000187:drug effects*; D002976:Clenbuterol / Q000494:pharmacology*; D004164:Diphosphonates / Q000494:pharmacology*; D008297:Male; D009132:Muscles / Q000187:drug effects / Q000201:enzymology; D009133:Muscular Atrophy / Q000517:prevention & control*; D005082:Physical Exertion; D011506:Proteins / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D014893:Weightlessness
D004164:Diphosphonates; D011506:Proteins; D019386:Alendronate; D002976:Clenbuterol