RANKL in the osteolysis of AES total ankle replacement implants.

Area of Science:

• Orthopedic Surgery
• Biomaterials Science
• Immunology

Background:

• Failed total ankle replacements (TAR) often exhibit early peri-implant osteolysis.
• The underlying mechanisms of this osteolysis are not fully understood.
• Receptor activator of nuclear factor kappa B ligand (RANKL) is implicated in bone resorption.

Purpose of the Study:

• To investigate the role of RANKL in peri-implant tissue reactions in failed TAR.
• To determine if RANKL mediates osteolysis by targeting implant debris or host tissues.

Main Methods:

• Analysis of peri-prosthetic tissues from failed TAR implants.
• Immunohistochemical staining for macrophages, RANKL, RANK, and osteoprotegerin (OPG).
• Comparison with control tissue samples.

Main Results:

• Failed TAR implants were surrounded by inflammatory tissues, including necrotic areas.
• CD163(+) macrophages and RANK(+) cells were frequently observed, often in proximity to RANKL(+) mesenchymal cells.
• Implant-derived wear debris was minimal; RANKL appeared to stimulate fusion of RANK-expressing cells, forming foreign body giant cells.
• OPG was mainly found in vascular endothelial cells.

Conclusions:

• Peri-implant osteolysis in early TAR failure is driven by RANKL-mediated chronic foreign body inflammation.
• This inflammation targets necrotic autologous tissues, not implant-derived particles.
• RANKL promotes the formation of multinuclear foreign body giant cells, contributing to osteolysis.