EFFECTS OF AMINOHYDROXYBUTANE BISPHOSPHONATE ON BONE-GROWTH WHEN ADMINISTERED AFTER HINDLIMB BONE LOSS IN TAIL-SUSPENDED RATS

The effects of aminohydroxybutane bisphosphonate (AHBuBP) on bone afte r disuse osteopenia were studied in tail-suspended rats. Male Sprague- Dawley rats (weight range, 313-352 g) randomized into four groups of e ight animals received 2 ml kg-1 day-1 of either AHBuBP (0.3 mg kg-1 da y-1) or normal saline (vehicle) subcutaneously on days 14 and 15 of a 28-day experiment. The groups were 1) nonsuspended, saline; 2) suspend ed 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 rec eived 15 mg/kg (1 ml/kg) of calcein. On day 28, they were sacrificed a nd their tibias and femurs were analyzed in vitro for bone density, st rength and stiffness. The tibias were also analyzed histomorphometrica lly. The tibias and femurs from AHBuBP-treated rats were as dense as t hose in the nonsuspended group, whereas tail suspension in the untreat ed rats for 14 and 28 days caused a significant decrease in bone densi ty. However, in measurements of bone strength and stiffness, the sampl es from the rats that received AHBuBP were similar to those of untreat ed rats suspended for 14 days, suggesting the newly formed bone was we aker. In the AHBuBP group, compared with all others, static histologic measurements of the proximal tibial metaphyses showed an increased bo ne area and perimeter and a decreased percentage of osteoid perimeter without a difference in the percentage of eroded perimeter. Dynamic hi stologic studies showed a decreased bone formation rate and decreased longitudinal growth rate. The retention of the first label was greates t in this group, which indicated a marked decrease in bone resorption. Although AHBuBP reduced normal bone formation, the net bone mass incr eased because of the greater inhibition of resorption, which resulted in bone with inferior mechanical strength.