Effects of aminohydroxybutane bisphosphonate on bone growth when administered after hind-limb bone loss in tail-suspended rats.
The effects of aminohydroxybutane bisphosphonate (AHBuBP) on bone after disuse osteopenia were studied in tail-suspended rats. Male Sprague-Dawley rats (weight range, 313-352 g) randomized into four groups of eight animals received 2 ml kg-1 day-1 of either AHBuBP (0.3 mg kg-1 day-1) or normal saline (vehicle) subcutaneously on days 14 and 15 of a 28-day experiment. The groups were 1) nonsuspended, saline; 2) suspended on days 14 to 28, saline; 3) suspended on days 0 to 28, AHBuBP; and 4) suspended on days 0 to 28, saline. On days 19 and 26, all rats received 15 mg/kg (1 ml/kg) of calcein. On day 28, they were sacrificed and their tibias and femurs were analyzed in vitro for bone density, strength and stiffness. The tibias were also analyzed histomorphometrically. The tibias and femurs from AHBuBP-treated rats were as dense as those in the nonsuspended group, whereas tail suspension in the untreated rats for 14 and 28 days caused a significant decrease in bone density. However, in measurements of bone strength and stiffness, the samples from the rats that received AHBuBP were similar to those of untreated rats suspended for 14 days, suggesting the newly formed bone was weaker. In the AHBuBP group, compared with all others, static histologic measurements of the proximal tibial metaphyses showed an increased bone area and perimeter and a decreased percentage of osteoid perimeter without a difference in the percentage of eroded perimeter. Dynamic histologic studies showed a decreased bone formation rate and decreased longitudinal growth rate.(ABSTRACT TRUNCATED AT 250 WORDS)
Apseloff
G
G
Department of Pharmacology, College of Medicine, Ohio State University, Columbus.
Girten
B
B
Weisbrode
S E
SE
Walker
M
M
Stern
L S
LS
Krecic
M E
ME
Gerber
N
N
D019386:Alendronate; D000818:Animals; D015519:Bone Density / Q000187:drug effects*; D001846:Bone Development / Q000187:drug effects*; D001851:Bone Diseases, Metabolic / Q000188:drug therapy*; D004164:Diphosphonates / Q000494:pharmacology*; D006614:Hindlimb; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D004164:Diphosphonates; D019386:Alendronate