Odanacatib, a New Drug for the Treatment of Osteoporosis: Review of the Results in Postmenopausal Women

Abstract

Osteoclasts are specialized cells that initiate the process of bone resorption, which has two phases, dissolution of the mineral component and degradation of the organic matrix, in which cathepsin K plays a key role. Cathepsin K inhibitors, which block the activity of cathepsin on bone resorption lacunae, may be a new therapeutic option in osteoporosis. Odanacatib is a nonpeptidic biaryl inhibitor of cathepsin K. Two studies have evaluated the efficacy and safety of odanacatib, a phase I study to determine the dose and a phase II study of safety and efficacy. Due to the long half-life of odanacatib and the similar effects of different doses on bone remodeling markers, a weekly dosage was chosen for the phase II trail, with the best results being obtained with a dose of 50 mg. At 36 months, increases in bone mineral density similar to those produced by other powerful antiresorptive drugs (zoledronate and denosumab) were observed but there were differences in the behaviour of bone remodeling markers. Data on fractures from the phase III trial currently in development are required to confirm these possible advantages.

Biochemical markers of bone turnover – uses and limitations

“…Cathepsin K, in particular, is expressed at the ruffled border of actively resorbing osteoclasts. 46 Osteoclasts secrete cathepsin K into bone resorption lacunae for degradation of bone matrix proteins including type I collagen, osteopontin and osteonectin, and hence, cathepsin K plays an important role in bone resorption. It is produced in a precursor form containing 329 amino acids, which is later cleaved to 215 amino acids to yield the active form.…”

Bone Restoration in Diabetic Osteolysis and Therapeutic Targets

“…Odanacatib, is a cathepsin K inhibitor, offers theoretical advantages over bisphosphonates. Since it does not reduce the number of osteoclasts and does not alter their function due the mechanism of action which different from that of other anti resorptive agents [60]. Receptor activator of NF-κ B ligand (RANKL)-induced formation of multinucleated osteoclasts is inhibited by Phloretin.…”

Risk of Fracture and Prevention and Treatment of Osteoporosis

“…Odanacatib, a new anti-resorptive drug, is a selective, reversible nonpeptidic biary1 inhibitor of cathepsin K. It has been shown to suppress bone resorption markers and increase BMD of the lumbar spine and total hip in patients with postmenopausal osteoporosis [41]. Odanacatib can suppress bone resorption whilst maintaining bone formation, an uncoupling effect in contrast to other anti-resorptive drugs [22].…”