Odanacatib (MK-0822) (Synonyms: MK-0822)

Cell experiment:

To assess cell survival, differentiated osteoclast (OC) at appr 7×104 cells/cm2 are re-seeded on bovine bone slices with or without 100 nM Odanacatib (ODN). Bone slices are fixed on days 2, 4, 6, and 12 with no media changes. Samples are stained for TRAP activity, and OC number.

Animal experiment:

Sixteen, 8-month-old, female Sprague-Dawley (SD) rats (weight, 385 ± 55 g) are given water and soft diet food ad libitum in a temperature-controlled environment with regular 12-h cycles of light and dark. The rats are randomised into 4 groups, with 4 rats in each group: sham group, OVX + Veh group, OVX + ODN-l group and OVX + ODN-h group. Following implant insertion, Odanacatib (ODN, 5 mg/mL) is administered to the OVX + ODN-l and OVX + ODN-h groups at concentrations of 1 mL/kg and 6 mL/kg, respectively, by gavaging once a day for 8 weeks. The OVX + Veh group is gavaged with 0.5% sodium carboxymethyl cellulose at a concentration of 6 mL/kg over the same duration. After the gavage administration, the rats of each group are sacrificed by injecting sodium pentobarbital intravenously. The implants are harvested and fixed in 10% buffered formalin together with the surrounding bone.

References:

[1]. Jacques Yves Gauthier, et al. The discovery of odanacatib (MK-0822), a selective inhibitor of cathepsin K. Bioorg Med Chem Lett. 2008 Feb 1;18(3):923-8.
[2]. Leung P, et al. The effects of the cathepsin K inhibitor odanacatib on osteoclastic bone resorption and vesicular trafficking. Bone. 2011 Oct;49(4):623-635.
[3]. Ng KW. Potential role of odanacatib in the treatment of osteoporosis. Clin Interv Aging. 2012;7:235-47.
[4]. Yi C, et al. Inhibition of cathepsin K promotes osseointegration of titanium implants in ovariectomised rats. Sci Rep. 2017 Mar 17;7:44682.