PATHOGENESIS AND PREVENTION OF ASEPTIC LOOSENING AFTER TOTAL HIP ARTHROPLASTY

Abstract

Aseptic loosening arises when periprosthetic bone loss results in mechanical failure at the host-implant interface, and is the main factor limiting implant survival after total hip arthroplasty (THA). The aims of this study were to determine whether genetic variation is a risk factor for loosening, explore the metabolic mechanisms of periprosthetic bone loss, and determine whether bisphosphonates may prevent bone loss and enhance implant mechanical stability after THA. In a genetic association study (J Bone Mineral Res2003; 18:1995–2001) we found that carriage of the −238A allele within the promoter region of the TNF gene was an independent risk factor for aseptic loosening. A subsequent reporter gene assay showed differential TNF gene responsiveness between the –238A and –238G alleles to polyethylene particule stimulation (Calcified Tissue Int 2003; 72: 251-273). In a cross-sectional study (J Orthop Res 2003; 214: 691–696) we found that subjects with aseptic loosening had lower bone mineral density (BMD) in the region of the femoral calcar and higher urinary excretion of cross-linked collagen breakdown products than their counterparts with fixed femoral implants. In a randomised controlled trial we found that a single dose infusion of a bisphosphonate (pamidronate) reduced femoral bone loss over 2 years after THA, but did not affect pelvic bone loss or implant migration (J Bone Miner Res2002; 17: 1328). Transient increases in bone turnover markers occurred after surgery and were highly predictive of later femoral BMD change. The main predictor of early implant migration was patient age, but not periprosthetic BMD change. In summary, genetic as well as environmental factors affect implant survival after THA. Aseptic loosening is associated with regional changes in bone mass and turnover as well as focal osteolytic lesions. Bisphosphonate therapy is well tolerated after THA and has a clear biological effect. However, the impact of preventing early bone loss on late aseptic loosening remains unclear and awaits long term study.

[Winner, Robert Jones Gold Medal and Association Prize, 2003]