Small molecule inhibitors of IkappaB kinase signaling inhibit osteoclast formation in vitro and prevent ovariectomy-induced bone loss in vivo.

The NFκB pathway plays a critical role in the regulation of osteoclast activity, and activation of the pathway is dependent on IκB kinase (IKK), which phosphorylates IκB, targeting it for proteasomal degradation. Pharmacological inhibitors of IKK exhibit anti-inflammatory properties and prevent bone erosions in models of inflammatory arthritis. However, the effects of these agents on osteoblast function and ovariectomy-induced bone loss remain unknown.