title: Long-term treatment with odanacatib maintains normal trabecular biomechanical properties in ovariectomized adult monkeys as demonstrated by micro-CT-based finite element analysis.
abstract: The cathepsin K inhibitor odanacatib (ODN) is a potent and reversible inhibitor of osteoclastic resorption activity. This drug is currently under development for the treatment of postmenopausal osteoporosis. Previously, we described data on the treatment efficacy of ODN in a preclinical estrogen-deficient model of an ovariectomized (OVX) rhesus monkey using HR-pQCT based finite element analysis (FEA) in vivo estimates of bone strength on the distal radius. To support the bone safety profile of ODN, we report ex vivo data on the apparent and hard tissue biomechanical properties of the trabecular bone of vertebrae of animals after 20 months of dosing in three treatment groups: Vehicle (VEH), ODN (2 mg/kg/day), and ALN (30 μg/kg/week). Biomechanical axial compression tests were performed on cylindrical trabecular samples cored out of the third lumbar vertebra of each animal at the end of the study. The biomechanical test results demonstrated that a normal (positive correlation between bone mineral density and bone strength) apparent material property relationship was maintained in the lumbar spine of ODN and ALN treated non-human primates (NHP). Trabecular bone hard tissue Young's modulus value was estimated using experimentally measured stiffness combined with FEA. The FEA and experimental results demonstrated that ODN treatment for 20 months maintained normal trabecular bone material hard tissue properties in the OVX-monkeys and was comparable to ALN.
authors.affiliation: MerckSharp and Dohme Corp., Whitehouse Station, NJ, USA.
authors.forename: Antonio
authors.initials: A
authors.lastname: Cabal
authors.affiliation: MerckSharp and Dohme Corp., Whitehouse Station, NJ, USA.
authors.forename: Donald S
authors.initials: DS
authors.lastname: Williams
authors.affiliation: MerckSharp and Dohme Corp., Whitehouse Station, NJ, USA.
authors.forename: Richa Y
authors.initials: RY
authors.lastname: Jayakar
authors.affiliation: MerckSharp and Dohme Corp., Whitehouse Station, NJ, USA.
authors.forename: Jingru
authors.initials: J
authors.lastname: Zhang
authors.affiliation: MerckSharp and Dohme Corp., Whitehouse Station, NJ, USA.
authors.forename: Swanand
authors.initials: S
authors.lastname: Sardesai
authors.affiliation: MerckSharp and Dohme Corp., Whitehouse Station, NJ, USA.
authors.forename: Le T
authors.initials: LT
authors.lastname: Duong
keywords: Finite element analysis; Odanacatib; micro-CT