The Receptor Activator for Nuclear Factor kappa B Ligand is believed to be an important molecule of bone metabolism. This is a natural and necessary surface-bound molecule on several types of cells, and serves to activate osteoclasts. Overproduction of RANKL is implicated in a variety of degenerative diseases. In patients with neuropathy, the RANKL/OPG pathway is thought to mediate the development of Neuropathic Osteoarthropathy or “Charcot Joint” An illustrative depiction of the RANKL pathway is as follows: Cellular stress or injury may result in expression of RANK Ligand on the surface of activated ostoblasts and T cells. In this example, an activated T cell is contacting a pre-osteoclast. Because this RANKL presenting cell is in an activated form, RANKL will become expressed, thus activate an uninhibited RANK receptor on the Surface of an Osteoclast. What is important to note, is that osteoprotegerin is a natural inhibitor of RANK and is thought to mediate a protective balance. Denosumab, and several other drugs, are being studied for their effects in preventing further transduction on the RANKL pathway and could prove to be useful in preventing disease progression. As the transduction cascade continues, IkB kinase is activated and subsequently phosphorylates the Inhibitor of kappa B, leaving Nuclear Factor kappa B free to diffuse uninhibited. Upon entering the nuclear membrane, Nuclear Factor kappa B will serve as a rapid-acting transcription factor, and will …
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