Inhibition of bone resorption with rankl binding peptides

A method for prevention and/or treatment of bone diseases and/or disorders by inhibiting bone resorption or osteoclast activity comprising administering a polypeptide that specifically binds Receptor Activator of Nuclear Factor kappa B Ligand (RANKL) to a subject, wherein the amount of the polypeptide administered is effective to change one or more markers of bone metabolism and/or bone homeostasis selected from cross-linking telopeptide of type I collagen (CTX-1), N-terminal telopeptide of type I collagen (NTX-1), tartrate-resistant acid phosphatase isoform 5b (TRACP5b), N-terminal propeptide of type I procollagen (P1NP) and bone-specific alkaline phosphatase (BAP), for at least 30 days after administration,

• wherein the polypeptide comprises two or more immunoglobulin single variable domains that specifically bind RANKL and that essentially consist of 4 framework regions (FR1 to FR4, respectively) and 3 complementarity determining regions (CDR1 to CDR3, respectively), in which CDR1 is chosen from SEQ ID NO:
• 1, CDR2 is chosen from SEQ ID NO:
• 2, and CDR3 is chosen from SEQ ID NO:
• 3, and
• wherein
• the polypeptide is administered in an amount from about 0.003 mg/kg to about 0.03 mg/kg and the serum levels of CTX-1 are reduced by 30% for at least about 30 days after administration;
• the polypeptide is administered in an amount from about 0.01 mg/kg to about 0.1 mg/kg and the serum levels of CTX-1 are reduced by 30% for at least about 120 days after administration;
• the polypeptide is administered in an amount from about 0.1 mg/kg to about 1 mg/kg and the serum levels of CTX-1 are reduced by 30% for at least about 270 days after administration;
• the polypeptide is administered in an amount of less than or equal to 0.03 mg/kg and the serum levels of CTX-1 are reduced by at least 45% for at least about 30 days after administration;
• the polypeptide is administered in an amount from about 0.01 mg/kg to about 3 mg/kg, preferably in an amount from about 0.01 mg/kg to about 0.1 mg/kg and the serum levels of CTX-1 are reduced by at least 45% for at least about 60 days after administration;
• the polypeptide is administered in an amount from about 0.01 mg/kg to about 0.3 mg/kg, preferably 0.03 mg/kg to about 0.3 mg/kg and the serum levels of CTX-1 are reduced by at least 45% for about 30 days to 3 months, preferably for at least about 90 days after administration;
• the polypeptide is administered in an amount from about 0.1 mg/kg to about 1 mg/kg and the serum levels of CTX-1 are reduced by at least 45% for at least about 120 days after administration;
• the polypeptide is administered in an amount from about 0.3 mg/kg to about 1 mg/kg and the CTX-1 is reduced by at least 45% for about 3 months to 6 months after administration;
• the polypeptide is administered in an amount of less than or equal to 0.3 mg/kg and the CTX-1 is reduced by at least 45% for about 3 months to 6 months after administration;
• the polypeptide is administered in an amount of less than or equal to 1 mg/kg and the serum levels of CTX-1 are reduced by at least 45% for about 6 months after administration;
• the polypeptide is administered in an amount from about 0.03 mg/kg to about 0.3 mg/kg and the serum levels of CTX-1 are reduced by at least 70% for at least about 30 days after administration;
• the polypeptide is administered in an amount from about 0.1 mg/kg to about 1 mg/kg and the serum levels of CTX-1 are reduced by at least 70% for at least about 120 days after administration;
• the polypeptide is administered in an amount from about 0.01 mg/kg to about 0.1 mg/kg and the levels of NTX-1 are reduced by at least 30% for at least 60 days after administration;
• the polypeptide is administered in an amount from about 0.03 mg/kg to about 0.3 mg/kg and the levels of NTX-1 are reduced by at least 30% for at least about 90 days after administration;
• the polypeptide is administered in an amount from about 0.1 mg/kg to about 1 mg/kg and the levels of NTX-1 are reduced by at least 30% for at least about 120 days after administration;
• the polypeptide is administered in an amount from about 1 mg/kg to about 10 mg/kg and the levels of NTX-1 are reduced by at least 30% for at least about 180 days (or 6 months), preferably at least 10 months, or even at least 12 months after administration;
• the polypeptide is administered in an amount from about 0.01 mg/kg to about 3 mg/kg, preferably in an amount from about 0.01 mg/kg to about 0.1 mg/kg and the levels of NTX-1 are reduced by at least 45% for at least about 30 days after administration;
• the polypeptide is administered in an amount from about 0.03 mg/kg to about 0.3 mg/kg and the levels of NTX-1 are reduced by at least 45% for at least about 60 days after administration;
• the polypeptide is administered in an amount from about 0.01 mg/kg to about 3 mg/kg, preferably, 0.01 mg/kg to about 0.3 mg/kg, or 0.03 mg/kg to about 0.3 mg/kg and the levels of NTX-1 are reduced by at least 45% for at least about 30 days to 3 months after administration;
• the polypeptide is administered in an amount of less than or equal to 0.03 mg/kg and the levels of NTX-1 are reduced by at least 45% for at least about 30 days to 3 months after administration;
• the polypeptide is administered in an amount from about 0.1 mg/kg to about 1 mg/kg and the levels of NTX-1 are reduced by at least 45%, compared to pre-treatment or normal levels, for at least about 150 days after administration;
• the polypeptide is administered in an amount from about 0.3 mg/kg to about 1 mg/kg and the levels of NTX-1 are reduced by at least 45% for about 3 months to 6 months after administration;
• the polypeptide is administered in an amount of less than or equal to 0.3 mg/kg and the levels of NTX-1 are reduced by at least 45% for about 3 months to 6 months after administration;
• the polypeptide is administered in an amount from about 1 mg/kg to about 10 mg/kg, preferably in an amount from about 1 mg/kg to about 3 mg/kg the levels of NTX-1 are reduced by at least 45% for at least 6 months to 1 year after administration;
• the polypeptide is administered in an amount of less than or equal to 1 mg/kg and the levels of NTX-1 are reduced by at least 45% for at least about 180 days (or 6 months) after administration;
• the polypeptide is administered in an amount from about 0.1 mg/kg to about 1 mg/kg and the levels of NTX-1 are reduced by at least 70% for at least about 30 days after administration;
• the polypeptide is administered in an amount from about 0.3 mg/kg to about 3 mg/kg and the levels of NTX-1 are reduced by at least 70% for at least about 90 days after administration;
• the polypeptide is administered in an amount from about 1 mg/kg to about 10 mg/kg and the levels of NTX-1 are reduced by at least 70% for at least about 120 days after administration;
• the polypeptide is administered in an amount from about 0.1 mg/kg to about 1 mg/kg, preferably in an amount from about 0.3 mg/kg to about 3 mg/kg, more preferably in an amount from about 0.3 mg/kg to about 1 mg/kg and the levels of NTX-1 are reduced by at least 80% for at least about 30 days (to 3 months) after administration;
• the polypeptide is administered in an amount from about 1 mg/kg to about 10 mg/kg and the levels of NTX-1 are reduced by at least 80%, compared to pre-treatment or normal levels, for at least about 90 days after administration;
• the polypeptide is administered in an amount from about 0.03 mg/kg to about 0.3 mg/kg and the serum levels of TRACP5b are reduced by at least 30% for at least about 60 days after administration;
• the polypeptide is administered in an amount from about 0.1 mg/kg to about 1 mg/kg and the serum levels of TRACP5b are reduced by at least 30% for at least about 90 days after administration;
• the polypeptide is administered in an amount from about 0.3 mg/kg to about 3 mg/kg and the serum levels of TRACP5b are reduced by at least 30% for at least about 120 days after administration;
• the polypeptide is administered in an amount from about 0.1 mg/kg to about 1 mg/kg and the serum levels of TRACP5b are reduced by at least 45% for at least about 30 days after administration;
• the polypeptide is administered in an amount from about 0.3 mg/kg to about 3 mg/kg and the serum levels of TRACP5b are reduced by at least 45%, compared to pre-treatment or normal levels, for at least about 90 days after administration;
• the polypeptide is administered in an amount from about 0.003 mg/kg to about 0.03 mg/kg and the serum levels of P1NP are reduced by at least 30% for at least about 90 days after administration;
• the polypeptide is administered in an amount from about 0.01 mg/kg to about 0.1 mg/kg and the serum levels of P1NP 1 are reduced by at least 30% for at least about 120 days after administration;
• the polypeptide is administered in an amount from about 0.03 mg/kg to about 0.3 mg/kg and the serum levels of P1NP are reduced by at least 45% for at least about 90 days after administration;
• or
• the polypeptide is administered in an amount from about 0.1 mg/kg to about 1 mg/kg and the serum levels of P1NP are reduced by at least 70% for at least about 90 days after administration.