Inhibition of cathepsin K for treatment of osteoporosis.
Cathepsin K is the protease that is primarily responsible for the degradation of bone matrix by osteoclasts. Inhibitors of cathepsin K are in development for treatment of osteoporosis. Currently available antiresorptive drugs interfere with osteoclast function. They inhibit both bone resorption and formation, due to the coupling between these processes. Cathepsin K inhibitors, conversely, target the resorption process itself and may not interfere with osteoclast stimulation of bone formation. In fact, when cathepsin K is absent or inhibited in mice, rabbits, or monkeys, bone formation is maintained or increased. In humans, inhibition of cathepsin K is associated with sustained reductions in bone resorption markers but with smaller and transient reductions in bone formation markers. The usefulness of cathepsin K inhibitors in osteoporosis is now being examined in phase 2 and phase 3 clinical trials of postmenopausal osteoporotic women.
Leuven University Division of Geriatric Medicine and Centre for Metabolic Bone Diseases, UZ Leuven campus Gasthuisberg, Herestraat 49, B-3000 Leuven, Belgium. steven.boonen@uzleuven.be
Steven
S
Boonen
Elizabeth
E
Rosenberg
Frank
F
Claessens
Dirk
D
Vanderschueren
Socrates
S
Papapoulos
D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology / Q000627:therapeutic use; D015519:Bone Density / Q000187:drug effects / Q000502:physiology; D016723:Bone Remodeling / Q000187:drug effects* / Q000502:physiology*; D001862:Bone Resorption / Q000503:physiopathology; D056657:Cathepsin K / Q000037:antagonists & inhibitors* / Q000502:physiology; D006801:Humans; D010024:Osteoporosis / Q000188:drug therapy* / Q000503:physiopathology; D015663:Osteoporosis, Postmenopausal / Q000097:blood; D053778:Thiazolidines / Q000494:pharmacology / Q000627:therapeutic use
D001713:Biphenyl Compounds; C560865:ONO-5334; D053778:Thiazolidines; D000469:Alkaline Phosphatase; D056657:Cathepsin K; C527128:odanacatib