Calcium phosphate cements comprising an osteoclastogenic agent

Abstract

Methods and compositions are provided for producing flowable compositions, e.g. pastes, that set into calcium phosphate products that include an osteoclastogenic agent. In the subject methods, dry reactants that include a calcium source and a phosphate source are combined with a setting fluid and an osteoclastogenic agent, e.g., RANKL or a mimetic thereof, and the combined reactants are mixed to produce the flowable composition. Also provided are the compositions themselves as well as kits for preparing the same. The subject methods and compositions produced thereby find use in a variety of applications, including hard tissue repair applications.

1 . A method of producing a flowable composition that sets into a calcium phosphate containing product, said method comprising: 
 combining:    (a) a setting fluid;    (b) dry reactants comprising a calcium source and a phosphate source; and    (c) an osteoclastogenic agent;    in a ratio sufficient to produce said flowable material.    
     
     
         2 . The method according to  claim 1 , wherein said setting fluid comprises said osteoclastogenic agent.  
     
     
         3 . The method according to  claim 1 , wherein said dry reactants comprise said osteoclastogenic agent.  
     
     
         4 . The method according to  claim 1 , wherein said osteoclastogenic agent comprises a modulator of the RANK mediated osteoclastogenesis induction pathway.  
     
     
         5 . The method according to  claim 4 , wherein said mediator is an ligand for RANK.  
     
     
         6 . The method according to  claim 5 , wherein said ligand for RANK is a RANKL polypeptide or mimetic thereof.  
     
     
         7 . The method according to  claim 4 , wherein said ligand is a RANKL polypeptide.  
     
     
         8 . The method according to  claim 7 , wherein said RANKL polypeptide is a human RANKL or a RANK binding fragment thereof.  
     
     
         9 . The method according to  claim 6 , wherein said ligand is a small molecule mimetic of RANKL.  
     
     
         10 . The method according to  claim 1 , wherein said ratio ranges from about 0.2:1 to 0.7:1.  
     
     
         11 . The method according to  claim 10 , wherein said flowable composition is a paste.  
     
     
         12 . The method according to  claim 1 , wherein said setting fluid is a solution of a soluble silicate.  
     
     
         13 . The method according to  claim 1 , wherein said flowable composition sets into said calcium phosphate containing product in a period of time ranging from about 5 to 10 minutes.  
     
     
         14 . The method according to  claim 1 , wherein said calcium phosphate containing product has a compressive strength ranging from about 25 to 100 MPa.  
     
     
         15 . A method of producing a paste that sets into a calcium phosphate containing product, said method comprising: 
 (a) combining: 
 (i) dry reactants comprising a calcium source and a phosphate source;  
 (ii) a setting fluid; and  
 (iii) an osteoclastogenic agent;  
 wherein said dry reactants, setting fluid and osteoclastogenic agent are combined in a ratio sufficient to provide for said paste; and  
   (b) mixing said combined reactants and setting fluid for a sufficient period of time to produce a paste capable of setting into a calcium phosphate containing product.    
     
     
         16 . The method according to  claim 15 , wherein said setting fluid comprises said osteoclastogenic agent.  
     
     
         17 . The method according to  claim 15 , wherein said dry reactants comprise said osteoclastogenic agent.  
     
     
         18 . The method according to  claim 15 , wherein said osteoclastogenic agent comprises a ligand for RANK.  
     
     
         19 . The method according to  claim 15 , wherein said ligand is a RANKL polypeptide or mimetic thereof.  
     
     
         20 . The method according to  claim 15 , wherein said setting fluid is a solution of a soluble silicate.  
     
     
         21 - 29 . (canceled)