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
3H-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
3H-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 3H-thymidine uptake by the macrophages.