title: [Reducing bone resorption by cathepsin K inhibitor and treatment of osteoporosis].
abstract: Cathepsin K is a lysosomal cysteine protease, secreted from osteoclasts. It plays a major role in the osteoclastic bone resorption by cleaving type 1 collagen, the major bone matrix protein, under acidic pH. In cathepsin K knockout mice, bone mineral density (BMD) is increased, bone resorption is decreased without reduction in the number of osteoclast whereas bone formation is decreased. Based on these results, cathepsin K inhibitors have been developed for the treatment of osteoporosis. Odanacatib is one of them and is perhaps closest for launching. In phase 1 and 2 trials, it markedly reduced bone resorption with a transient reduction in bone formation, thus resulted in a robust increase in both trabecular and cortical BMD in osteoporotics. Currently, Odanacatib is in phase 3 fracture prevention trial, of which results are anticipated in 2014.
authors.affiliation: Third Department of Medicine, Teikyo University Chiba Medical Center, Japan.
authors.forename: Reiko
authors.initials: R
authors.lastname: Watanabe
authors.forename: Ryo
authors.initials: R
authors.lastname: Okazaki
mesh_terms: D000818:Animals; D001713:Biphenyl Compounds / Q000627:therapeutic use; D015519:Bone Density / Q000187:drug effects* / Q000502:physiology; D016723:Bone Remodeling / Q000187:drug effects / Q000502:physiology; D001862:Bone Resorption / Q000188:drug therapy / Q000378:metabolism; D056657:Cathepsin K / Q000037:antagonists & inhibitors* / Q000235:genetics; D006801:Humans; D010024:Osteoporosis / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D001713:Biphenyl Compounds; D056657:Cathepsin K; C527128:odanacatib