Apoptosis in interface membranes of aseptically loose total hip arthroplasty

The terminal events leading to periprosthetic osteolysis are multifactorial in nature and modulation of this process after the stage of osteolytic med iator release has been futile. Recently, the demonstration of the ability o f bisphosphonates to inhibit bone resorption that is mediated by particle-s timulated macrophages and their induction of osteoclast apoptosis suggests a potent area for modulation of osteolysis at the prosthesis-bone interface . The purpose of this study was to determine the mode of cell death that oc curs at the osteolytic interface of failed total hip arthroplasty (THA). TU NEL staining, DNA laddering, and immunodetection of poly(ADP-ribose)polymer ase (PARP) protein were used to identify the presence of apoptosis in inter face membranes from 25 patients aged 28-88 years old (mean, 58 years) harve sted at the time of hip revision surgery. Our results demonstrated positive TUNEL stain in 100% of specimens with an average 37% of cells (range 12-60 %) positively stained for TUNEL whereas less than 8% of control tissue cell s showed positive staining. DNA laddering, a characteristic feature of apop totic cells, was observed in 82% (28/34) of specimens studied at both the a cetabular and femoral side of aseptically loose THAs. No laddering was obse rved in control tissues. Finally, using Western blot analysis, we observed the appearance of the 89 kDa PARP fragment associated with apoptosis in 92% of specimens (30/33). Our results demonstrate the presence of apoptotic ce ll death in interface membranes of THAs suggesting that apoptosis-related e vents are indeed associated with periprosthetic osteolysis and could serve as a specific target point for therapeutic modulation. (C) 2001 Kluwer Acad emic Publishers.