Wear particle-induced inflammatory bone loss (osteolysis) is the leading cause of total hip arthroplasty (THA) failure. Individual susceptibility to osteolysis is modulated by genetic variation. In this 2-stage case-control association study we examined whether variation within candidate genes in inflammatory and bone turnover signaling pathways associates with susceptibility to osteolysis and time to prosthesis failure. We examined two cohorts, comprising 758 (347 male) Caucasian subjects who had undergone THA with a metal on polyethylene bearing couple; 315 of whom had developed osteolysis. Key genes within inflammatory, bone resorption, and bone formation pathways were screened for common variants by pairwise-SNP tagging using a 2-stage association analysis approach. In the discovery cohort four SNPs within RANK, and one each within KREMEN2, OPG, SFRP1, and TIRAP (p < 0.05) were associated with osteolysis susceptibility. Two SNPs within LRP6, and one each within LRP5, NOD2, SOST, SQSTM1, TIRAP, and TRAM associated with time to implant failure (p < 0.05). Meta-analysis of the two cohorts identified four SNPs within RANK, and one each within KREMEN2, OPG, SFRP1, and TIRAP associated with osteolysis susceptibility (p < 0.05). Genetic variation within inflammatory signaling and bone turnover pathways may play a role in susceptibility to osteolysis. ß 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:193-198, 2015.Keywords: arthroplasty; genetics; hip; innate immunity; osteolysis A recent meta-analysis of worldwide joint replacement register data has shown that 12% of first (primary) THRs fail within 10 years of implantation, requiring revision surgery. 1 Adverse local tissue reactions to prosthesis materials characterized by periprosthetic osteolysis and resulting in prosthesis loosening accounts for 60% of these failures. 2 Osteolysis arises as a cell-mediated adverse inflammatory immune response to the wear debris materials shed from the implant surfaces. 3,4 Several investigators have shown that particulate debris from prosthetic materials initiate inflammatory signaling through pattern recognition receptors (PRR) including NOD-like and toll-like receptors (TLRs). [5][6][7][8][9] The NOD-like receptor NALP3 (NACHT-, LRR-, and pyrin domain-containing protein 3) is thought to play a central role in the inflammasome complex of proteins that sense and initiate pro-inflammatory responses to danger or pathogen-associated molecular patterns. 5,7 Furthermore, these PRRs are expressed in osteolytic membrane taken from patients with failing prostheses. 10,11 Bone turnover is closely regulated by the equilibrium between osteoblasts and osteoclasts that is regulated by the interplay between the Wnt and RANK signaling pathways. 12,13 P2 purinergic receptors are important regulators of both inflammation and bone remodeling. 14 Patients vary in their osteolytic response to particulate wear debris. 15 Macrophage responses to a particulate challenge in-vitro varies between indivi...
Background: The purpose of the present study was to evaluate the results of the Sheffield bone block procedure for anteroinferior bone loss in traumatic shoulder instability. In this modified open technique, the medial half of coracoid process without its soft tissue attachments is used to provide congruent augmentation of the anteroinferior glenoid and secured with two screws. Methods: In this retrospective consecutive case series , all patients having recurrent traumatic instability with glenoid bone loss > 20% and/or a large Hill-Sachs lesion were included. The shoulder function was evaluated clinically and by Oxford Shoulder Instability Score (OSIS; by post/telephone). Results: There were 84 patients in this series with a large proportion engaged in contact sports. Mean (range) age was 33 years (16 years to 45 years); male : female, 59 : 8; mean (range) follow-up period was 48 months (36 months to 84 months) and the response rate 89% (75/84). Mean postoperative OSIS was 43 (33 to 46) and one patient had re-dislocation (1.3%). No neurovascular complications/hardware failure/non-union/infections were noted. By 6 months, 85% patients had returned to pre-injury sport and 93% had returned to pre-injury work. Conclusions: The Sheffield bone block procedure provides reliable and satisfactory results in patients having recurrent instability with glenoid bone loss and/or a large Hill-Sachs lesion with minimal complications and an excellent chance of returning to original sport and occupation.
Background Periprosthetic osteolysis resulting in aseptic loosening is a leading cause of THA revision. Individuals vary in their susceptibility to osteolysis and heritable factors may contribute to this variation. However, the overall contribution that such variation makes to osteolysis risk is unknown. Questions/purposes We conducted two genome-wide association studies to (1) identify genetic risk loci associated with susceptibility to osteolysis; and (2) identify genetic risk loci associated with time to prosthesis revision for osteolysis. Methods The Norway cohort comprised 2624 patients after THA recruited from the Norwegian Arthroplasty Registry, of whom 779 had undergone revision surgery for osteolysis. The UK cohort included 890 patients previously
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