Methods of altering bone growth by administration of sost or wise antagonist or agonist
The present invention provides a method of promoting local bone growth by administering a therapeutic amount of a Sost antagonist to a mammalian patient in need thereof. Preferably, the Sost antagonist is an antibody or FAB fragment selectively recognizing any one of SEQ ID NOS: 1-23. The Sost antagonist may be coadministered together or sequentially with a matrix conducive to anchoring new bone growth. Orthopedic and Periodontal devices comprising an implantable portion adapted to be permanently implanted within a mammalian body and bearing an external coating of a Sost antagonist are also disclosed, as it a method of increasing bone density by administering to a mammalian patient a therapeutic amount of a Sost antagonist together with an antiresorptive drug.
1. A method of promoting local bone growth, comprising the steps of administering a therapeutic amount of a Sclerostin antagonist implanted locally to a mammalian patient in need thereof, wherein said Sclerostin antagonist comprises an antibody or FAB fragment specifically binding a peptide comprising 10 contiguous amino acids of a sequence selected from the group consisting of SEQ ID NOs: 2-13, 22 and 23, and wherein the antibody interferes with Sclerostin's ability to bind to LRP, thereby providing new local bone formation, wherein said Sclerostin antagonist is implanted in said patient while being affixed to a medical device or a matrix material.
2. The method according to claim 1 , further comprising the step of administering to said mammalian patient a biocompatible matrix or scaffold conducive to anchoring new bone growth.
3. The method according to claim 2 , wherein said biocompatible matrix or scaffold comprises a material selected from the group consisting of an osteo-conducive scaffold containing a calcium salt, calcium sulfate, autograft, hydroxyapatite, demineralized bone, allograft or tricalcium phosphate.
4. A method of promoting bone according to claim 1 , further comprising the steps of administering locally to said mammalian patient a BMP recombinant protein.
5. The method according to claim 4 , further comprising the step of administering to said mammalian patient a biocompatible matrix or scaffold conducive to anchoring new bone growth.
6. The method according to claim 5 , wherein said biocompatible matrix or scaffold comprises a material selected from the group consisting of a scaffold containing a calcium salt, calcium sulfate, autograft, hydroxyapatite, demineralized bone, allograft or tricalcium phosphate.
7. The method according to any one of claims 4 - 6 , wherein said antibody or FAB fragment is a monoclonal antibody.
8. The method according to claim 7 , wherein said antibody is a humanized antibody or FAB fragment.
9. The method according to any one of claims 1 - 6 , wherein said Sclerostin antagonist comprises an antibody or FAB fragment specifically binding SEQ ID NO:23.
10. The method according to claim 9 , wherein said antibody or FAB fragment is a monoclonal antibody.
11. The method according to claim 10 , wherein said antibody is a humanized antibody or FAB fragment.
12. A method of systemically increasing bone density, comprising the steps of administering, to a mammalian patient in need thereof, a therapeutic comprising an effective amount of a Sclerostin antagonist together with an antiresorptive drug, wherein said Sclerostin antagonist comprises an antibody or FAB fragment specifically binding a peptide comprising 10 contiguous amino acids of a sequence selected from the group consisting of SEQ ID NOs: 2-13, 22 and 23, and wherein the antibody interferes with Sclerostin's ability to bind to LRP, thereby systemically increasing bone density.
13. The method according to claim 12 , wherein the therapeutic is administered by implantation.
14. The method according to claim 12 , wherein said antiresorptive drug is denosumab, a bisphosphonate, a SERM, calcitonin, a calcitonin analog, Vitamin D, a vitamin D analog, or a Rank antagonist.
15. The method according to any one of claims 12 or 13 , wherein said antibody or FAB fragment is a monoclonal antibody.
16. The method according to claim 15 , wherein said antibody is a humanized antibody or FAB fragment.
17. The method according to claim 16 , wherein said antiresorptive drug is denosumab, a bisphosphonate, a SERM, calcitonin, a calcitonin analog, Vitamin D, a vitamin D analog, or a Rank antagonist.
18. The method according to any one of claims 12 or 13 , wherein said Sclerostin antagonist comprises an antibody or FAB fragment specifically binding SEQ ID NO: 23.
19. The method according to claim 18 , wherein said antibody or FAB fragment is a monoclonal antibody.
20. The method according to claim 19 , wherein said antibody is a humanized antibody or FAB fragment.
21. The method according to claim 20 , wherein said antiresorptive drug is denosumab, a bisphosphonate, a SERM, calcitonin, a calcitonin analog, Vitamin D, a vitamin D analog, or a Rank antagonist.
22. The method according to claim 1 , wherein said antibody or FAB fragment interferes with Sclerostin's ability to bind to LRP5 or LRP6.
23. The method according to claim 12 , wherein said antibody or FAB fragment interferes with Sclerostin's ability to bind to LRP5 or LRP6.
24. The method according to claim 15 , wherein said antiresorptive drug is denosumab, a bisphosphonate, a SERM, calcitonin, a calcitonin analog, Vitamin D, a vitamin D analog, or a Rank antagonist.
25. The method according to claim 18 , wherein said antiresorptive drug is denosumab, a bisphosphonate, a SERM, calcitonin, a calcitonin analog, Vitamin D, a vitamin D analog, or a Rank antagonist.
26. The method according to claim 19 , wherein said antiresorptive drug is denosumab, a bisphosphonate, a SERM, calcitonin, a calcitonin analog, Vitamin D, a vitamin D analog, or a Rank antagonist.
27. The method according to claim 26 , wherein said antibody is a humanized antibody or FAB fragment.