Odanacatib reduces bone turnover and increases bone mass in the lumbar spine of skeletally mature ovariectomized rhesus monkeys

Odanacatib (ODN) is a selective and reversible inhibitor of cathepsin K (CatK) currently being developed as a once‐weekly treatment for osteoporosis. In this study, we evaluated the effects of ODN on bone turnover, bone mineral density (BMD), and bone strength in the lumbar spine of estrogen‐deficie...

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Bibliographic Details
Published in:Journal of bone and mineral research 2012-03, Vol.27 (3), p.509-523
Main Authors: Masarachia, Patricia J, Pennypacker, Brenda L, Pickarski, Maureen, Scott, Kevin R, Wesolowski, Gregg A, Smith, Susan Y, Samadfam, Rani, Goetzmann, Jason E, Scott, Boyd B, Kimmel, Donald B, Duong, Le T
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Biphenyl Compounds - pharmacology
Bone Density Conservation Agents - pharmacology
Bone Remodeling - drug effects
CATHEPSIN K INHIBITOR
Female
Fundamental and applied biological sciences. Psychology
Lumbar Vertebrae - drug effects
Macaca mulatta
NONHUMAN PRIMATE
Organ Size - drug effects
OSTEOCLAST
OSTEOPENIA
OSTEOPOROSIS
Ovariectomy
Primates
Skeleton and joints
Vertebrates: osteoarticular system, musculoskeletal system
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Summary:Odanacatib (ODN) is a selective and reversible inhibitor of cathepsin K (CatK) currently being developed as a once‐weekly treatment for osteoporosis. In this study, we evaluated the effects of ODN on bone turnover, bone mineral density (BMD), and bone strength in the lumbar spine of estrogen‐deficient, skeletally mature rhesus monkeys. Ovariectomized (OVX) monkeys were treated in prevention mode for 21 months with either vehicle, ODN 6 mg/kg, or ODN 30 mg/kg (p.o., q.d.) and compared with intact animals. ODN treatment persistently suppressed the bone resorption markers (urinary NTx [75% to 90%] and serum CTx [40% to 55%]) and the serum formation markers (BSAP [30% to 35%] and P1NP [60% to 70%]) versus vehicle‐treated OVX monkeys. Treatment with ODN also led to dose‐dependent increases in serum 1‐CTP and maintained estrogen deficiency–elevated Trap‐5b levels, supporting the distinct mechanism of CatK inhibition in effectively suppressing bone resorption without reducing osteoclast numbers. ODN at both doses fully prevented bone loss in lumbar vertebrae (L1 to L4) BMD in OVX animals, maintaining a level comparable to intact animals. ODN dose‐dependently increased L1 to L4 BMD by 7% in the 6 mg/kg group (p 
ISSN:0884-0431
1523-4681
DOI:10.1002/jbmr.1475