The findings presented herein are consistent with the lack of effect of L-006235 on bone erosion in a model of inflammatory arthritis,41 which contrast the beneficial effects of OPG-Fc on this feature in the inflammatory arthritis model.34 Overall, the differences in the effects of OPG-Fc vs L-006235 on joint features in these models of 2 different types of arthritis suggest that mechanisms additional to cathepsin K also contribute to changes in joint structure. This evidence concerns the gene TNFRSF11B and arthritic joint disease.