Two decades ago, researchers identified numerous members of the tumor necrosis factor (TNF) superfamily of cytokine receptors. Among them, the receptor activator of nuclear factor kappa B (RANK) has since emerged as a central player in bone physiology and beyond.
Maintaining the Bone Niche
In order to repair and maintain the skeleton and ensure adequate levels of calcium in the body, bone is constantly being synthesized and destroyed. This complex process of remodeling is orchestrated by 2 major cell types: the osteoblasts (which build up the bone) and the osteoclasts (which break it down).
Table. Selected Clinical Trials of Denosumab in Cancer
aTrial ongoing but not recruiting participants.
bTrial not yet open for recruitment.
A plethora of different molecules produced by the bone and its surrounding environment maintain a tight balance of osteoblast and osteoclast function. As researchers sought to tease out the underlying molecular mechanisms, the RANK receptor, a member of the TNF superfamily, and its only known receptor RANKL, emerged front and center in the bone remodeling process through their effects on osteoclasts.
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