Future therapeutic targets in osteoporosis.
OBJECTIVE
To describe new agents for the treatment of osteoporosis, discuss a conceptual framework of agents that are antiresorptive or anabolic, and review pathways that affect bone turnover and steps in those pathways that are targets for new therapeutic agents.


RESULTS
Novel antiresorptive agents are being developed. Denosumab, a fully human mononoclonal antibody to receptor activator of nuclear factor kappa B ligand, has completed its major fracture trial. Assessment of odanacatib, an inhibitor of cathepsin K, an osteoclast enzyme required for resorption of bone matrix, is underway. Glucagon-like peptide 2 is an intestinal peptide that prevents the nocturnal rise in bone resorption. Anabolic agents act by stimulating new bone formation. Novel anabolic agents in development include antibodies that target molecules (sclerostin and Dkk1) involved in Wnt signaling, a pathway that regulates gene transcription of proteins that are important for osteoblast function. An antagonist to the calcium-sensing receptor and an activin receptor fusion protein, which functions as an activin antagonist, have shown promise as anabolic agents in early human trials.


CONCLUSIONS
This review discusses potential future advances in drug therapy for osteoporosis including novel antiresorptive and anabolic agents that may become available in the coming years.
Deal
Chad
C
Center for Osteoporosis and Metabolic Bone Disease, Department of Rheumatology, Orthopedic and Rheumatology Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA. dealc@ccf.org
D028341:Activins / Q000037:antagonists & inhibitors / Q000378:metabolism; D045930:Anabolic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D050071:Bone Density Conservation Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D056657:Cathepsin K; D002403:Cathepsins / Q000037:antagonists & inhibitors / Q000378:metabolism; D053767:Glucagon-Like Peptide 2 / Q000494:pharmacology; D006801:Humans; D010024:Osteoporosis / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D053245:RANK Ligand / Q000037:antagonists & inhibitors / Q000378:metabolism; D051153:Wnt Proteins / Q000187:drug effects / Q000378:metabolism
D045930:Anabolic Agents; D050071:Bone Density Conservation Agents; D053767:Glucagon-Like Peptide 2; D053245:RANK Ligand; C505688:TNFSF11 protein, human; D051153:Wnt Proteins; D028341:Activins; D002403:Cathepsins; C534130:CTSK protein, human; D056657:Cathepsin K