A review of UHMWPE wear-induced osteolysis: the role for early detection of the immune response

Abstract

In a world where increasing joint arthroplasties are being performed on increasingly younger patients, osteolysis as the leading cause of failure after total joint arthroplasty (TJA) has gained considerable attention. Ultra-high molecular weight polyethylene wear-induced osteolysis is the process by which prosthetic debris mechanically released from the surface of prosthetic joints induces an immune response that favors bone catabolism, resulting in loosening of prostheses with eventual failure or fracture. The immune response initiated is innate in that it is nonspecific and self-propagating, with monocytic cells and osteoclasts being the main effectors. To date, detecting disease early enough to implement effective intervention without unwanted systemic side effects has been a major barrier. These barriers can be overcome using newer in vivo imaging techniques and modules linked with fluorescence and/or chemotherapies. We discuss the pathogenesis of osteolysis, and provide discussion of the challenges with imaging and therapeutics. We describe a positron emission tomography imaging cinnamoyl-Phe-(D)-Leu-Phe-(D)-Leu-Phe-Lys module, specific to macrophages, which holds promise in early detection of disease and localization of treatment. Further research and increased collaboration among therapeutic and three-dimensional imaging researchers are essential in realizing a solution to clinical osteolysis in TJA.

Figure 1

Hormonal regulation of osteoclastogenesis. Upon M-CSF and RANKL stimulation, OCPs undergo differentiation into giant, mature osteoclasts expressing TRAP and CATK.

Figure 2

Effects of major cytokines involved in osteolysis. Note the repetitive and propagative properties of the immune response. RANKL, TNF-α, and IL-1β also inhibit osteoclast apoptosis.

Figure 3

Binding assay of NIRF probe cFLFLF-PEG-Cy7 to RAW264.7 cells stimulated by 1 μg·mL⁻¹ lipopolysaccharide vs no treatment (NT). (a) Various concentrations of the probe were applied to the assay, including (from top to bottom) 1.0, 0.5, 0.1 and 0.05 μmol·L⁻¹. Results indicate that fluorescent intensity strengthened with increasing doses of the probe, and that LPS was able to enhance binding affinity of the probe for cells. (b) A blocking test was performed with cFLFLF and a Scramble peptide (cLFFFL), revealing that the binding signal was blocked by cFLFLF but not controls.