Effects of eight-month treatment with ONO-5334, a cathepsin K inhibitor, on bone metabolism, strength and microstructure in ovariectomized cynomolgus monkeys

Future directions for new medical entities in osteoporosis

“…High resolution peripheral computer tomography analyses of the distal radius also indicate an increase of cortical thickness at this site in monkeys [51] (which can be different from human radius as it is likely to be more weight-bearing in monkeys, depending on their housing conditions). Similar results on improved bone mass and in particular femur cortical bone volume have recently been reported in ovariectomized monkeys receiving ONO-5334, another potent cathepsin K inhibitor, for 8 months [52]. ONO-5334 was equivalent to alendronate on improving vertebral bone strength but superior to alendronate on femur neck strength.…”

Effects of Long-Term Odanacatib Treatment on Bone Gene Expression in Ovariectomized Adult Rhesus Monkeys: Differentiation From Alendronate

“…Surprisingly, the overall responses to each treatment showed similar patterns of gene expression regulation in both tibial regions, suggesting that the treatment‐related transcriptional changes could be predominantly driven by cellular constituents within cortical bone after 20 months of therapy. In NHPs, ALN has been reported to reduce endocortical and intracortical remodeling and shows little effect on periosteal modeling of the long bones . On the other hand, ODN has been shown to improve cortical dimension and strength in the central femur of NHPs, primarily by maintaining endocortical and increasing periosteal bone formation and mildly reducing intracortical remodeling …”

Novel therapies for osteoporosis

“…A difference of all CatK inhibitors from other antiresorptives, seen with relacatib [62], ODN [64], and ONO-5334 [65], is that despite the reduced bone resorption, the number and vitality of the osteoclasts is maintained or even increased, as evidenced by serum TRAP5b levels, a marker of osteoclast number and function [62,64,65].…”

“…In ovariectomized (OVX) rabbits or monkeys, CatK inhibitors decreased bone resorption without affecting bone formation, increased trabecular and cortical BMD, enlarged the cortical area of the femur and the cortical thickness of the proximal tibia, and improved mechanical properties at the spine and femur [62][63][64][65].…”