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.