An imbalance in bone formation relative to bone resorption results in the net bone loss that occurs in osteoporosis and inflammatory bone diseases. Although it is well known that RANKL/RANK stimulate bone resorption by activating nuclear factor-kB (NF-kB) in osteoclasts, the molecular mechanisms that mediate impaired bone formation are poorly understood.

The authors of a recent study [1] show that the time- and stage-specific inhibition of endogenous inhibitor of kB kinase (IKK)-NF-kB in differentiated osteoblasts substantially increases trabecular bone mass and bone mineral density without affecting osteoclast activities in young mice. Moreover, inhibition of IKK–NF-kB in differentiated osteoblasts maintains bone formation, thereby preventing osteoporotic bone loss induced by ovariectomy in adult mice. Inhibition of IKK–NF-jB enhances the expression of Fos-related antigen-1 (Fra-1), an essential transcription factor involved in bone matrix formation in vitro and in vivo.

Taken together, these results suggest that targeting IKK–NF-kB may help to promote bone formation in pathological situations such as osteoporosis and other bone diseases.

1. Chang J et al. Nature Med. 2009;15:682-689.