Osteoprotegerin (OPG) has been reported to be a novel protein that can suppress osteoclast differentiation and activation. This study examined the therapeutic effects of OPG on established periprosthetic osteolysis in a rat model.

A bone cement prosthesis was inserted into the rat femur and polyethylene particles were continuously infused into the knee joint using an osmotic pump. After osteolysis was established in four weeks, rats were intravenously injected with vehicle (control group) or 1 mg/kg of OPG (OPG-1 group) or 10 mg/kg of OPG (OPG-10 group) every week until they were sacrificed at 8 weeks. Effects of direct injections of OPG into the knee joint were also investigated. Periprosthetic bone resorption was evaluated with bone mineral density and histomorphometric analysis of membranes composed of total area of interface membrane and inflammatory grading. Radiographs were evaluated for focal osteolysis with a blind manner.

Periprosthetic bone resorption was significantly suppressed in OPG-10 group compared to the other groups (p < 0.05). Histomorphometric analyses showed less total area as well as less inflammatory grading of the interface membrane in OPG-10 group compared to other groups (p < 0.01). Radiographic osteolysis appeared to decrease in number in OPG-10 group. Direct injections of OPG into the knee joint appeared to be more effective compared to intravenous injections.

The present study demonstrates that OPG has significantly restored the established periprosthetic osteolysis in our animal model. OPG may be a possible agent to retain the bone stock before revision surgery for failed prostheses. Conclusion: This study demonstrates that osteoprotegerin suppresses the progression of periprosthetic osteolysis and restores bone stock in a rat model.

This study examined the inhibitory effects of anti-TNF-a antibody (anti-TNF) and a new bisphosphonate (TRK-530) on peri-implant oseteolysis in a rat model with continuous infusion of polyethylene particles. TRK-530 is a novel synthetic bisphophonate to have a direct effect on osteoclastic bone resorption as well as suppressive effects on bone resorbing cytokines from macrophages.

Materials and methods: Sixty Wister rats were randomized to three groups (n=20 each). In each rat, a Kirshner wire (K-wire) was inserted into the femur and polyethylene particles (HDPE, mean size; 2 microns) were continuously infused into the knee joint using an osmotic pump. The animals were subcutaneously injected with saline (control group) or 1 mg/kg of TRK (TRK group) or intraperitoneally injected with 100 mg of anti-TNF (anti-TNF group) every second day after surgery until 8 weeks. At 4 weeks or 8 weeks after surgery, rats were sacrificed. Rdiographs were evaluated for the presence of osteolysis, thereafter, garnulation tissues were stored for PCR analysis for IL-1 mRNA as well as TNF-a mRNA. Then, femurs were prepared for the histology.

Results: Radiographic peri-implant osteolysis was seen more frequently in TRK group compared to other two groups (p< 0.01). The interfacial membrane was significantly thinner in TRK and anti-TNF group compared to the control group (p< 0.01). The average number of osteoclasts around K-wire was significantly fewer in the TRK group compared to the other groups (p< 0.01). The expression of IL-1 mRNA and TNF-a mRNA was significantly suppressed in the TRK group at 8 weeks after surgery.

Discussion: The present study demonstrates that cumulative effects of TRK such as the suppression of bone resorbing cytokines as well as direct suppression of osteoclasts reduce the polyethylene induced peri-implant osteolysis. In addition, single anti-cytokine therapy appears not to be enough to inhibit peri-implant osteolysis in our model.