title: Cathepsin K inhibitors: a novel target but promising approach in the treatment of osteoporosis.
abstract: Osteoporosis is a pathologic process characterized by low bone mass with skeletal fragility and an increased risk of fracture. It occurs due to an imbalance between bone resorption and formation. Although current antiresorptive therapy halts bone loss, it does not cure the condition as it also inhibits bone formation. Recent preclinical and clinical trials suggest that the inhibition of resorption by cathepsin K inhibitors increases bone formation. Cathepsin K is a papainlike cysteine protease with high potent collagenase activity and predominantly expressed in osteoclasts. While allowing demineralization, cathepsin K inhibitors suppress the degradation of type I collagen (the major organic matrix of bone) and thus enhancing bone formation. Many of these inhibitors have passed preclinical studies and are presently in clinical trials at different stages of advancement. This review explores the promising role of cathepsin K as a novel antiresorptive for the treatment of osteoporosis.
authors: Pharmacology Department, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, 50300 Kuala lumpur, Malaysia. isa@medic.ukm.my.
authors: Asadul Mazid
authors: AM
authors: Helali
authors: Farhana Matin
authors: FM
authors: Iti
authors: Isa Naina
authors: IN
authors: Mohamed
mesh_terms: D000818:Animals; D015519:Bone Density / Q000187:drug effects; D001862:Bone Resorption / Q000188:drug therapy*; D056657:Cathepsin K / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002986:Clinical Trials as Topic; D024042:Collagen Type I / Q000378:metabolism; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D010010:Osteoclasts / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects; D015663:Osteoporosis, Postmenopausal / Q000175:diagnosis / Q000188:drug therapy*
chemical_list: D024042:Collagen Type I; D015853:Cysteine Proteinase Inhibitors; D056657:Cathepsin K