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Inhibiting cathepsin K in mice: impact on fracture repair


Cathepsin K inhibitors (CatK-Is) are able to prevent bone loss in animal models and in patients with osteoporosis; in this study Soung et al. investigated whether L-006235(L-235), a lysosomotropic CatK-I, was able to facilitate bone repair in a mouse model of bone fracture. Its effects were compared to those of the bisphosphonate alendronate (ALN).

Radiographic studies, including micro-CT analyses at days 0, 7, 10, 14, 21 and 28 after experimentally induced fracture, showed that treatment with L-235 delayed bone remodeling compared to ALN and controls, but did not inhibit callus formation or bridging. Mice treated with L-235 showed enhanced bone formation, but the remodeling of cartilaginous callus during fracture repair was slower than in mice treated with ALN. L-235 also inhibited osteoclastic activity while increasing the numbers of tartrate-resistant acid phosphatase positive osteoclasts present.

Levels of serum N-terminal propeptide of type I procollagen were lower and the osteoblast surface of the calluses formed during healing was smaller in ALN-treated mice compared to controls and those treated with L-235.

Editor’s comment: This study is interesting as it documents similar effects on callus size and mineralization using a CatK-I and ALN. However, bone formation in the CatK-I group was better maintained in the calluses and the rest of the skeleton. The potential advantages on mechanical properties require exploration.

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