Different schedules of administration of (3 amino-1-hydroxypropylidene)-1, 1 bisphosphonate induce different changes in pig bone remodeling

Intermittent administration of antiosteoclastic agents has been proposed in order to increase trabecular bone volume (TBV). We evaluated the effect of two different intermittent schedules of administration of (3 amino-1-hydroxypropylidene)-1, 1 bisphosphonate (AHPrBP) on pig bone remodeling for a period of 60 days. AHPrBP (1.6 mumol/kg/injection) was given subcutaneously daily (group A1), or 5 consecutive days out of 21 days (group A2), or 1 out of every fourth day (group A3). Compared to control animals, group A1 significantly increased trabecular bone volume (TBV) (+62%) with a marked decrease in bone resorption assessed by interstitial bone thickness. Bone formation assessed by mean wall thickness (MWT) was also decreased due to a decrease in the number and activity of osteoblasts. There was not a delay in the coupling mechanism as assessed by the reversal surfaces. The two groups receiving intermittent schedules had markedly different results. Group A2 had very similar changes to group A1 despite receiving four time less drug. Compared to group A1 and A2, group A3 had smaller decrease in resorption and higher bone formation rate with identical MWT. These differences between group A2 and A3 were associated with similar levels of parathyroid hormone and vitamin D metabolites. Different bone concentrations induced by the two different schedules of AHPrBP may explain the greater effect on bone resorption and osteoblast recruitment in group A2 and thus a milder effect of the AHPrBP administration once every fourth day.