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 for promoting bone growth in a human subject being treated with a humanized sclerostin-recognizing antibody, comprising administering an antiresorptive drug to the subject.
2. The method of claim 1 , wherein the subject has previously been treated with the antiresorptive drug.
3. The method of claim 1 , wherein the subject is being treated with the humanized sclerostin-recognizing antibody subcutaneously.
4. The method of claim 1 , wherein the antiresorptive drug is a bisphosphonate, calcitonin, Vitamin D, or selective estrogen receptor modulator (SERM).
5. The method of claim 1 , wherein the antiresorptive drug is Vitamin D.
6. The method of claim 1 , wherein the antibody is formulated in a pharmaceutical composition.
7. The method of claim 6 , wherein the pharmaceutical composition comprises a pharmaceutically acceptable carrier selected from the group consisting of: water, saline, buffers, solvents, vehicles, oils, polyethylene glycols, glycerin, propylene glycol, carbohydrates, antioxidants, chelating agents, low molecular weight proteins, proteins, amino acids, stabilizers, excipients, and antibacterial agents.
8. The method of claim 7 , wherein the buffer comprises acetate, the carbohydrate comprises sucrose, and the pharmaceutically acceptable carrier comprises a polyethylene glycol.
9. The method of claim 1 , wherein the subject is being treated with the humanized sclerostin-recognizing antibody subcutaneously, the antibody is a sclerostin blocking antibody, and the antiresorptive drug is Vitamin D.
10. The method of claim 1 , wherein the administration of the antiresorptive drug results in increased bone formation relative to bone formation prior to administration of the humanized sclerostin-recognizing antibody and the antiresorptive drug.
11. The method of claim 1 , wherein the administration of the antiresorptive drug results in increased bone formation relative to a human subject not being treated with the humanized sclerostin-recognizing antibody.
12. The method of claim 1 , wherein the antiresorptive drug comprises at least one of bisphosphonate, calcitonin, Vitamin D, or SERM.
13. The method of claim 12 , wherein the antiresorptive drug is Vitamin D.
14. The method of claim 1 , wherein the antiresorptive drug is serially administered to the human subject being treated.
15. A method for increasing bone density in a human subject with low bone mass being treated with a sclerostin-recognizing antibody, comprising serially administering an antiresorptive drug to the subject.
16. The method of claim 15 , wherein the sclerostin is human sclerostin having the sequence of SEQ ID NO:22.
17. The method of claim 15 , wherein the sclerostin-recognizing antibody is humanized.
18. The method of claim 15 , wherein the human subject has at least one of osteoporosis and low bone density.
19. The method of claim 15 , wherein the antiresorptive drug comprises at least one of bisphosphonate, calcitonin, Vitamin D, or SERM.
20. The method of claim 15 , wherein the antiresorptive drug is Vitamin D.
21. The method of claim 15 , wherein the human subject has previously been treated with an antiresorptive drug.
22. The method of claim 15 , wherein the human subject has not previously been treated with an antiresorptive drug.
23. The method of claim 15 , wherein the antiresorptive drug is administered alone.
24. The method of claim 15 , wherein the antiresorptive drug is administered alone and following the human subject with low bone mass being treated with the sclerostin-recognizing antibody.