Osteoclasts have been identified as a key cellular target in the treatment of many diseases including osteoporosis, particle-induced osteolysis in total joint arthroplasty, and tumor-induced osteolysis. As such, anti-osteoclastic agents are a hot topic of orthopaedic research.
Calcitonin and Osteoprotegerin are naturally occuring cytokines which act either on cell surface receptors (calcitonin receptor) or bind soluable mediators (RANK-L) to inhibit osteoclasts. While two forms of bisphosphonates exist, both function to induce osteoclast apoptosis (programmed cell death). Denosumab is a monoclonal antibody to RANK-L which when given subcutaneously, binds and sequesters RANK-L, preventing it from stimulating RANK, a pro-osteoclastic receptor.
Schoppet et al wrote a comprehensive review of osteoprotegerin or OPG, a cytokine produced by many cells including osteoblasts and marrow stromal cells. It is a vital component in regulating bone resorption as it inhibits both osteoclast activation and differentiation by acting as a decoy receptor for RANK-L. The mechanism of RANK-L is seen in Illustration A.
Schoppet M, Preissner KT, Hofbauer LC. RANK ligand and osteoprotegerin: paracrine regulators of bone metabolism and vascular function. Arterioscler Thromb Vasc Biol. 2002 Apr 1;22(4):549-53.
PMID: 11950689 (Link to Abstract)