STUDIES OF THE MECHANISM BY WHICH THE MECHANICAL FAILURE OF POLYMETHYLMETHACRYLATE LEADS TO BONE-RESORPTION

The purpose of this study was to examine the relationship between the mechanical failure of polymethylmethacrylate and bone resorption at the bone-cement interface of a prosthesis. Evaluation of tissue that had been retrieved from the cement-bone interface of eighteen femoral components of total hip prostheses that were loose without associated infection revealed that a critical factor associated with bone resorption was the presence of particles that were small enough (one to twelve micrometers) to be phagocytized by macrophages. To study this phenomenon in vitro, macrophages in tissue culture were exposed to three preparations of polymethylmethacrylate cement. A novel method of cement preparation was used with control for solid and soluble contaminants, which provided a sensitive and specific technique for the determination of which mediators were released from the macrophages. Electron microscopy demonstrated phagocytosis of particles of less than twelve micrometers in size, regardless of the type of cement preparation. Exposure to all three cement preparations resulted in toxicity, as reflected by inhibition of H-3-thymidine incorporation. Exposure also led to increased release of tumor necrosis factor, but none of the three preparations resulted in release of prostaglandin E2. Division of the cement preparations into two groups on the basis of the size of the particles demonstrated that exposure to particles that were small enough to be phagocytized led to inhibition of H-3-thymidine incorporation and release of tumor necrosis factor, while exposure to particles that were too large to be phagocytized did not. Neither exposure to small particles nor exposure to large particles of cement led to release of prostaglandin E2. Our results show that when the mechanical failure of cement produces particles that are small enough to be phagocytized, phagocytosis of the particles results in the increased production of tumor necrosis factor by the macrophages, which may in turn lead to bone resorption and prosthetic loosening. These small particles also decrease H-3-thymidine uptake by the macrophages. CLINICAL RELEVANCE: The information obtained from this study and the use of this model may provide a means for the evaluation of the potential efficacy of pharmacological agents in terms of their capacity to slow the loosening process by selectively inhibiting the mediators of bone resorption that are produced after phagocytosis of polymethylmethacrylate particles. In addition, this model may be useful in the development of alternatives to cement in that it allows a comparison of the toxicity of polymethylmethacrylate with that of the test material. It also permits a comparison of the mediator production by macrophages exposed to polymethylmethacrylate with that of macrophages exposed to the test material. If these strategies delay the onset of clinical loosening, they might eliminate the need for revision operations in some patients and extend the indications for arthroplasty with cement to a younger age-group.