In vivo, autopsy, and clinical studies have shown that bulk cement or polymethylmethacrylate appears to be very well tolerated and does not appear to induce a significant foreign body reaction. Examination of autopsy material shows no adverse effect on human endosteal bone, and osseo-integration can and does occur. Long-term clinical studies support these conclusions and clearly demonstrate the importance of technique when using surgical bone cement. Fragmentation of bone cement results in the generation of particulate debris, which is phagocytosized by macrophages. Either through cell activation or cell injury, a variety of enzymes, prostaglandins, and cytokines, capable of stimulating osteoclasts, resulting in bone resorption, are released. Also, there is new evidence that suggests “activated macrophages” may play a direct role in bone resorption.