Figure 1. Processes that lead to debris particle-induced osteolysis. As joint implants wear, debris triggers processes that lead to inflammation and osteolysis. Together, these processes cause the implant to loosen and fail.

Macrophages are the primary target of debris particles from an implant. These cells take up debris via phagocytosis and secrete cytokines and chemokines in response [a]. One of these secreted cytokines, macrophage colony-stimulating factor 1 (CSF1; M-CSF), activates colony-stimulating factor 1 receptor (CSF1R; C-FMS; CD115) on osteoclast precursors [b].

When M-CSF is present with another factor, receptor activator of NF-kB ligand (RANKL; TNFSF11), osteoclast precursors differentiate into bone-resorbing osteoclasts [c]. RANKL activates tumor necrosis factor receptor superfamily member 11a (TNFRSF11A; RANK; CD265) and is produced by other cells such as T lymphocytes.

In addition to promoting osteoclast generation, the cytokines and chemokines secreted by the macrophage also attract additional macrophages, osteoclast precursors and other proinflammatory cells to the area [d].

As reported in Mediero et al., adenosine A2A receptor (ADORA2A) agonists can block the inflammation- and osteolysis-promoting effects of wear debris particles and thus have the potential to prevent joint implant failure.