BoneKEy Reports | BoneKEy Watch
Odanacatib, a cathepsin K inhibitor, superior to alendronate
DOI:10.1038/bonekey.2013.160
Cabal et al. compared the treatment efficacy of 2 mg/kg/day odanacatib (ODN) with 30 μg/kg/week alendronate (ALN) in non-human primates, using high-resolution peripheral CT (HR-pQCT), to test for bone strength, quality and density at the ultradistal radius 3, 6, 9, 12 and 18 months from baseline. Significant increases in total bone volume fraction (13.5%), cortical thickness (24.4%), integral volumetric bone mineral density (13.5%), peak stress (17.1%) and finite element analysis (FEA)-estimated peak force (26.6%) were observed in the animals treated with ODN at the 18-month time point. Each of these increases was significantly higher than the corresponding value measured in animals treated with ALN.
In a separate study, Williams et al. compared ODN and ALN treatment in ovariectomized rhesus monkeys. Animals that received a dose of ODN comparable with a human therapeutic dose showed significant improvement in cortical bone mineral density at the femoral neck, and increased cortical bone mineral content and cortical thickness at the sub-trochanteric proximal femur compared to those treated with ALN (P<0.05).
Editor’s comment: These two studies provide further evidence of the quantitatively different effects of ODN (a selective and reversible inhibitor of cathepsin K) and the bisphosphonate ALN on radius and hip cortical bone. Of particular note is the significantly greater increase of cortical thickness that occurs with ODN. Taken together with the results from an HR-pQCT study in post-menopausal women, they support ODN as the more effective therapy for improving bone strength at these sites.
This work is licensed under a
Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 United States License.