Osteoprotegerin inhibits in vitro mouse osteoclast formation induced by joint fluid from failed total hip arthroplasty

Osteoprotegerin (OPG) is a key regulator of osteoclastogenesis. We investig ated the presence of OPG and bone-resorbing cytokines, the potential of ost eoclastic differentiation in joint fluid from failed total hip arthroplasty (THA), and the inhibitory effect of OPG on osteoclast formation in vitro i nducted by the joint fluid. The study was aimed to clarify one important st ep in the cascade of periprosthetic osteolysis in the process of implant lo osening. OPG levels in failed THA joint fluid of 20 cases were significantl y lower than osteoarthritis (OA) joint fluid of 15 cases (p < 0.001), The l evels of bone-resorbing cytokines, interleukin (IL)-1 beta, and IL-6 were s ignificantly higher in failed THA joint fluid than OA fluid (p < 0.001 and p = 0.001, respectively). Marked osteoclast formation was observed in the p resence of failed THA joint fluid in the mouse coculture system, when compa red to OA fluid (p < 0.001), The addition of 100 ng/mL OPG to the mouse coc ulture system completely inhibited osteoclast formation in the presence of failed TWA joint fluid (p < 0.001), The data suggest that low levels of OPG combined with higher IL-1 beta and IL-6 levels represent the potential of osteoclast differentiation and its activation in failed THA joint fluid. In hibition of osteoclastogenesis in vitro by OPG suggests that a low level of OPG with elevated bone resorbing cytokines contributes to periprosthetic o steolysis via osteolytic joint fluid, thus leading to THA prosthesis loosen ing. (C) 2001 John Wiley & Sons. Inc.