New therapeutics for osteoporosis.
Two new approaches for the treatment of osteoporosis are summarized, each having arisen out of important new discoveries in bone biology. Odanacatib (ODN) inhibits the enzyme, cathepsin K, that is essential for the resorbing activity of osteoclasts. It is effective in preventing ovariectomy-induced bone loss in preclinical studies, and a phase II clinical study has shown inhibition of resorption sustained over five years. Outcome of a phase III study is awaited. The finding from mouse and human genetics that Wnt signaling is a powerful inducer of bone formation led to developments aimed at enhancing this pathway. Of the several approaches towards this, the most advanced is with a neutralizing antibody against sclerostin, the osteocyte-derived inhibitor of Wnt signaling. Preclinical studies show a powerful bone anabolic effect, and a clinical phase II study shows dose-dependent increases in bone formation and decreases in bone resorption markers.
University of Melbourne, Department of Medicine, St. Vincent's Institute of Medical Research, 9 Princes Street, Fitzroy 3065, Victoria, Australia.
Kong Wah
KW
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University of Melbourne, Department of Medicine, St. Vincent's Institute of Medical Research, 9 Princes Street, Fitzroy 3065, Victoria, Australia. Electronic address: jmartin@svi.edu.au.
T John
TJ
Martin
D048868:Adaptor Proteins, Signal Transducing; D045930:Anabolic Agents / Q000627:therapeutic use; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology / Q000627:therapeutic use; D050071:Bone Density Conservation Agents / Q000627:therapeutic use; D019485:Bone Morphogenetic Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D056657:Cathepsin K / Q000037:antagonists & inhibitors / Q000378:metabolism; D005819:Genetic Markers; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D010024:Osteoporosis / Q000188:drug therapy* / Q000378:metabolism; D010281:Parathyroid Hormone / Q000627:therapeutic use; D051153:Wnt Proteins / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D045930:Anabolic Agents; D001713:Biphenyl Compounds; D050071:Bone Density Conservation Agents; D019485:Bone Morphogenetic Proteins; C501126:DKK1 protein, human; D005819:Genetic Markers; D036341:Intercellular Signaling Peptides and Proteins; D010281:Parathyroid Hormone; C422903:SOST protein, human; D051153:Wnt Proteins; D038362:Glycogen Synthase Kinase 3; D056657:Cathepsin K; C527128:odanacatib