Figure 3.

Potential therapeutic strategies to treat bone resorption: agents that block the differentiation or activity of osteoclasts are potential therapeutic agents. Osteoprotegerin (OPG) inhibits the differentiation of osteoclasts through its action as a decoy receptor that blocks receptor activator of nuclear factor-kappa B (NF-κB) ligand (RANKL) and RANK juxtacrine interaction. Non-steroidal anti-inflammatory drugs (NSAIDs) and other anti-inflammatory molecules (including p38 mitogen-activated protein kinase inhibitors, c-jun N-terminal kinase inhibitors, NF-κB inhibitors, and the specific, high-affinity IL-1 inhibitor IL-1 [TRAP]) can inhibit the formation of hemato-progenitor cells to preosteoclasts. Antibodies to RANKL can also block this interaction. MMP inhibitors reduce the protease degradation of the organic matrix, and anti-integrins block the initial osteoclast adhesion to the matrix. Bisphosphonates and MMP inhibitors work at the site of the osteoclast adhesion zone to the mineralized matrix in blocking bone resorption. M-CSF = macrophage colony-stimulating factor; sRANKL = soluble RANKL; TNFsRC = TNF soluble receptor. Adapted with permission from Blackwell Publishing.¹⁵