Human bones are in a continuous process of remodeling that ensures renovation and maintenance of the skeletal mass. Bone remodeling has two phases that are normally coupled and balanced:
bone resorption mediated by osteoclasts and bone formation mediated by osteoblasts. An increase in
bone resorption over bone formation results in a progressive loss of bone mass and impairment of bone microarchitecture leading to
osteoporosis and its associated fractures. Recent advances in the understanding of the molecular and cellular mechanisms involved in the remodeling process have allowed the development of new targets for
osteoporosis treatment.
Cathepsin K, a
cysteine protease, is found in osteoclasts along the
bone resorption surfaces and very efficiently degrades
type I collagen, the major component of the organic bone matrix. Inhibition of
cathepsin K reduces
bone resorption but does not impair bone formation particularly at cortical sites.
Odanacatib, a potent and highly selective
cathepsin K inhibitor, showed prevention of bone loss without reduction of bone formation in preclinical and clinical trials (phase I and II).
Odanacatib is currently in a phase III fracture outcome international trial for the treatment of
postmenopausal osteoporosis.