Quantitative morphometric evaluation of the inhibitory activity of new aminobisphosphonates on bone resorption in the rat.
Three new bisphosphonates of various chain length, namely, 4-amino-1-hydroxybutylidene-1,1-bisphosphonate (AHBuBP), 5-amino-1-hydroxypentylidene-1,1-bisphosphonate (AHPeBP), and 6-amino-1-hydroxyhexylidene-1,1-bisphosphonate (AHHexBP) were compared with 3-amino-1-hydroxypropylidene-1,1-bisphosphonate (AHPrBP), and dichloromethylene bisphosphonate as to their effect on metaphyseal bone remodeling in the rat. The parameters assessed were growth in length, mineralization, metaphyseal density, mean trabecular diameter, and number of trabeculae. Both metaphyseal density, an index of metaphyseal Ca balance, and number of trabeculae, an index of bone resorption, showed the following sequence of potency: AHBuBP greater than AHPrBP = AHPeBP = AHHexBP greater than Cl2MBP. All compounds decreased trabecular diameter somewhat, an index of bone formation, with AHBuBP decreasing the least. AHBuBP and possibly AHHexBP appear to be interesting new bisphosphonates for future clinical use.
D000818:Animals; D001862:Bone Resorption / Q000187:drug effects*; D004164:Diphosphonates / Q000494:pharmacology* / Q000633:toxicity; D004353:Drug Evaluation, Preclinical; D005260:Female; D008903:Minerals / Q000378:metabolism; D009336:Necrosis; D051381:Rats; D011919:Rats, Inbred Strains; D012867:Skin / Q000187:drug effects / Q000473:pathology; D013329:Structure-Activity Relationship; D013977:Tibia / Q000033:anatomy & histology / Q000187:drug effects / Q000254:growth & development
D004164:Diphosphonates; D008903:Minerals