A RANDOMISED, DOUBLE-BLINDED CONTROLLED TRIAL OF THE EFFECT OF ALEDRONATE ON OSTEOCLASTOGENIC CYTOKINE EXPRESSION IN PATIENTS UNDERGOING REVISION SURGERY FOR ASEPTIC LOOSENING OF CEMENTED PRIMARY TOTAL HIP PROSTHESES.

Abstract

Introduction: Aseptic osteolysis represents a significant challenge to the orthopaedic surgeon as it limits the long terms survivorship of prosthetic implants.

Aim: To investigate whether the bisphosphonate aledronate alters the cytokine profile in the psuedomembrane excised from individuals undergoing revision hip arthroplasty surgery for aseptic failure.

Methods: A prospective, double-blinded, randomised controlled trial was conducted with relevant ethical approval. 10 patients were randomly assigned to receive a placebo or alendronate 70mg for a 6 week period prior to revision surgery. All individuals had aseptic failure of primary cemented femoral stems and acetabular cups with UHDPE inserts. Infection was excluded in all individuals prior to surgery. Multiple tissue samples were subsequently excised at surgery and sent for histology and culture. If either was subsequently positive for infection the individual was excluded from the study. Tissue samples were preserved using liquid nitrogen and formalin. Frozen tissue was stored at −70^oC pending Polymerase Chain Reaction analysis. Formalin preserved samples were paraffin sectioned for immunohistochemical analysis. PCR was carried out to assess expression of mRNA for Interleukins 1,6,17,18; TNF alpha, RANK-L, OPG and RANK. IHC was performed to confirm protein expression in the pseudomembrane excised from the femur and acetabulum. Multiple samples were used in each patient.

Results: In the 5 individuals who received the placebo there was expression of mRNA and protein for Interleukins 1,6,17,18; TNF alpha; RANK-L; OPG and RANK in all cases. There was no statistically significant difference in the expression of any of the aforementioned cytokines/receptors in the group receiving alendronate.

Discussion: A six seek course of oral alendronate 70mg had no effect upon osteoclastogenic cytokine expression when compared to the placebo group. This would suggest that alendronate may offer little benefit in reversing established particle induced osteolysis.