Methods and compositions for stimulating bone growth using nitric oxide releasing bisphosphonate conjugates (no-bisphosphonate)

Abstract

The invention relates to compositions and methods for use in treating skeletal system disorders in a vertebrate at risk for bone loss, and in treating conditions that are characterized by the need for bone growth, in treating fractures, and in treating cartilage disorders. More specifically, the invention concerns the use of NO-bisphosphonate assembly for enhancing bone growth.

1 . A compound comprising NO-(4-amino-1-hydroxybutylidene)bis-phosphonate (NO-alendronate), NO-(3-Amino-1-hyroxypropylidene)bis-phosphonate (NO-pamidronate), NO-(Dichloromethylene)-bis-phosphonate, (NO-clodronate), NO-[1-Hydroxy-2(3-pyridinyl)-ethylidene]-bis-phosphonate (NO-risedronate), NO-[1-Hydroxy-2-(1H-imidazole-1-yl)ethylidene]-bis-phosphonate (NO-zolondronate), NO-(1-Hydroxyethylidene)-bis-phosphonate (NO-etidronate), NO-[1-Hydroxy-3-(methylpentylamino)propylidene]-bis-phosphonate (NO-ibandronate), NO-[[(4-Chlorophenyl)thio]methylene]-bis-phosphonate (NO-tiludronate), NO-(6-Amino-1-hydroxyhexylidene)-bis-phosphonate (NO-neridronate), NO-([3-(Dimethylamino)-1-hydroxypropylidene]-bis-phosphonate (NO-olpadronate), NO-[(Cycloheptylamino)-methylene]-bis-phosphonate (NO-icadronate), or NO-[1-Hydroxy-2-imidazo-(1,2-a)pyridine-3-ylethylidene]-bis-phosphonate (NO-YH529).  
     
     
         2 . A pharmaceutical compound comprising the compound of  claim 1  and a pharmaceutically acceptable carrier or excipient.  
     
     
         3 . The pharmaceutical compound of  claim 2 , further comprising an additional agent formulated in a single pharmaceutical formulation.  
     
     
         4 . The pharmaceutical compound of  claim 3 , wherein the additional agent enhances bone growth or decreases bone resorption.