3-Amino-1-hydroxypropylidine-1-bisphosphonate (AHPrBP) suppresses not only the induction of new, but also the persistence of existing bone-forming surfaces in rat cancellous bone

Abstract

Although bone formation is coupled to resorption in both man and the rat, it is not known whether similar mechanisms are involved in these two species. To investigate this, we have attempted to further characterise the suppression of bone formation by the potent bone resorption inhibitor 3-amino-1-hydroxypropylidine-1-bisphosphonate (AHPrBP) in ovariectomised adult female rats. To see whether AHPrBP affects the activity of preexisting bone forming surfaces, as opposed to preventing the induction of new forming surfaces, three consecutive fluorochrome labels were administered 3, 10, and 17 days prior to sacrifice. The percentage of trabecular surface covered by first and second labels only (arrested surface), second and third labels only (induction surface), and all three labels (persisting surface) were recorded at the secondary spongiosa of the proximal tibial metaphysis. As expected, ovariectomy increased the proportion of induction surfaces, with AHPrBP preventing this increase. However, AHPrBP also reduced the proportion of persisting surfaces, implying inhibition of the activity of preexisting boneforming surfaces. We conclude that resorption inhibitors such as AHPrBP inhibit bone formation in the rat in a manner which appears inconsistent with the site-specific coupling seen in the adult human skeleton.