Fsh and fsh receptor modulator compositions and methods for inhibiting osteoclastic bone resorption and bone loss in osteoporosis

Abstract

The invention discloses compositions and methods for decreasing osteoclast which are useful for the treatment of a variety of bone loss disorders.

1 .- 8 . (canceled) 
     
     
         9 . A pharmaceutical composition for decreasing osteoclast activity and/or osteoclast differentiation in a subject, comprising:
 at least one of a follicle stimulating hormone modulator (FSHM) or a follicle stimulating hormone receptor modulator (FSHRM) in an amount effective to reduce bioactivity or bioavailability of follicle stimulating hormone in a subject,   at least one second therapeutic agent that treats a bone loss disorder in a subject; and   a pharmaceutically acceptable carrier.   
     
     
         10 . The composition of  claim 9 , wherein the at least one follicle stimulating hormone modulators or follicle stimulating hormone receptor modulators are selected from the group consisting of small molecules, proteins, peptides, antibodies, nucleic acids, and combinations thereof. 
     
     
         11 . The composition of  claim 9 , wherein the at least one follicle stimulating hormone modulators or follicle stimulating hormone receptor modulators are selected from the group consisting of siRNA, antibodies, and combinations thereof. 
     
     
         12 . The composition of  claim 9 , wherein the follicle stimulating hormone receptor modulator comprises (7-[4-[Bis-(2-carbamoyl-ethyl)-amino]-6-chloro-(1,3,5)-triazin-2-ylamino)-4-hydroxy-3-(4-methoxy-phenylazo)-naphthalene]-2-sulfonic acid. 
     
     
         13 . The composition of  claim 9 , wherein the follicle stimulating hormone modulator comprises an aminoalkylamide FSH antagonist. 
     
     
         14 . The composition of  claim 9 , wherein the follicle stimulating hormone receptor modulator comprises a thiazolidinone FSH receptor antagonist. 
     
     
         15 . The composition of  claim 9 , wherein the at least one second therapeutic agent is selected from the group consisting of estrogen, estrogen agonists, estrogen antagonists, estrogen receptor modulators, bisphosphonates, calcitonin, parathyroid hormone, cathepsin K inhibitors, integrin inhibitors, src inhibitors, V-ATPase inhibitors, bone binding transition metals, chloride channel inhibitors, GnRH modulators and combinations thereof. 
     
     
         16 . The composition of  claim 9 , wherein the at least one second therapeutic agent comprises estrogen. 
     
     
         17 . A composition for decreasing osteoclast activity and/or osteoclast differentiation in a subject, comprising:
 at least one of an anti-follicle stimulating hormone antibody or an anti-follicle stimulating hormone receptor antibody; and   at least one second therapeutic agent that treats a bone loss disorder in a subject.   
     
     
         18 . The composition of  claim 17 , wherein at least one of the anti-follicle stimulating hormone antibody or the anti-follicle stimulating hormone receptor antibody is a monoclonal antibody. 
     
     
         19 . The composition of  claim 17 , wherein at least one of the anti-follicle stimulating hormone antibody or the anti-follicle stimulating hormone receptor antibody is a humanized antibody. 
     
     
         20 . The composition of  claim 17 , wherein at least one of the anti-follicle stimulating hormone antibody or the anti-follicle stimulating hormone receptor antibody is a human antibody. 
     
     
         21 . The composition of  claim 17 , wherein the second therapeutic agent comprises one or more follicle stimulating hormone modulators or follicle stimulating hormone receptor modulators selected from the group consisting of small molecules, proteins, peptides, nucleic acids, and combinations thereof. 
     
     
         22 . The composition of  claim 21 , wherein the follicle stimulating hormone modulator or follicle stimulating hormone receptor modulator comprises siRNA. 
     
     
         23 . The composition of  claim 21 , wherein the follicle stimulating hormone receptor modulator comprises (7-[4-[Bis-(2-carbamoyl-ethyl)-amino]-6-chloro-(1,3,5)-triazin-2-ylamino)-4-hydroxy-3-(4-methoxy-phenylazo)-naphthalene]-2-sulfonic acid. 
     
     
         24 . The composition of  claim 21 , wherein the follicle stimulating hormone modulator comprises an aminoalkylamide FSH antagonist. 
     
     
         25 . The composition of  claim 21 , wherein the follicle stimulating hormone receptor modulator comprises a thiazolidinone FSH receptor antagonist. 
     
     
         26 . The composition of  claim 17 , wherein the second therapeutic agent is selected from the group consisting of estrogen, estrogen agonists, estrogen antagonists, estrogen receptor modulators, bisphosphonates, calcitonin, parathyroid hormone, cathepsin K inhibitors, integrin inhibitors, src inhibitors, V-ATPase inhibitors, bone binding transition metals, chloride channel inhibitors, GnRH modulators and combinations thereof. 
     
     
         27 . The composition of  claim 17 , wherein the second therapeutic agent comprises estrogen. 
     
     
         28 . A kit for decreasing osteoclast activity and/or osteoclast differentiation in a subject, comprising:
 one or more dosages of at least one of an anti-follicle stimulating hormone antibody or an anti-follicle stimulating hormone receptor antibody;   one or more dosages of a second therapeutic agent; and   instructions for administering to a subject the one or more dosages of the at least one of an anti-follicle stimulating hormone antibody or an anti-follicle stimulating hormone receptor antibody, and the one or more dosages of the second therapeutic agent.   
     
     
         29 . A packaged formulation for decreasing osteoclast activity and/or osteoclast differentiation in a subject, comprising:
 a therapeutically effective amount of at least one of an anti-follicle stimulating hormone antibody or an anti-follicle stimulating hormone receptor antibody;   a therapeutically effective amount of a second therapeutic agent; and   a pharmaceutically acceptable carrier.