Analysis of surgically retrieved periproslhetic lissue and investigation with experimental models of debris-indueed osteolysis strongly suggest that osteodast lineage eells, either mononuelear or multinuclcar, are involved in periprosthetie osteolysis (66).

As ostcoclasl lineage cells require RANK-RANKL, signaling for survival, one conceptually attractive approach to halt or prevent cell-mediated, debris induced periprosthetie osteolysis is through in vivo blockade of RANK-RANKL signaling (66).

A third molecule, osteoprotegrin (OPG), has been discovered. This molecule negatively regulates RANKL signaling. OPG is a soluble tumor necrosis factor (TNF) receptor family molecule that can sequester RANKL and therefore inhibit RANK'S capacity to signal through RANKL. The absence of the interaction of RANKL with RANK induces apoptosis in osteo-cHsts_an_d osteoclast progenitors, resulting in death of _osteoclast lineage cells (Fig. 23) (66).

Osteoclast precursors

Wear Particles

RAN

Osteoproteqerm (OPG)

RANKb

Stromal eel!

1

Fig. (23) Cellular mechanism of osieolysis (66)

Elucidation of the roles of OPG and RANKL in the regulation of osteoclastogenesis has provided an ideal drug target to prevent osteolysis

(71).