RESUMO
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 recruited from hospitals in the north of England, 317 who either had radiographic evidence of and/or had undergone revision surgery for osteolysis. All participants had received a fully cemented or hybrid THA using a small-diameter metal or ceramic-on-conventional polyethylene bearing. Osteolysis susceptibility case-control analyses and quantitative trait analyses for time to prosthesis revision (a proxy measure of the speed of osteolysis onset) in those patients with osteolysis were undertaken in each cohort separately after genome-wide genotyping. Finally, a meta-analysis of the two independent cohort association analysis results was undertaken. RESULTS: Genome-wide association analysis identified four independent suggestive genetic signals for osteolysis case-control status in the Norwegian cohort and 11 in the UK cohort (p ≤ 5 x 10). After meta-analysis, five independent genetic signals showed a suggestive association with osteolysis case-control status at p ≤ 5 x 10 with the strongest comprising 18 correlated variants on chromosome 7 (lead signal rs850092, p = 1.13 x 10). Genome-wide quantitative trait analysis in cases only showed a total of five and nine independent genetic signals for time to revision at p ≤ 5 x 10, respectively. After meta-analysis, 11 independent genetic signals showed suggestive evidence of an association with time to revision at p ≤ 5 x 10 with the largest association block comprising 174 correlated variants in chromosome 15 (lead signal rs10507055, p = 1.40 x 10). CONCLUSIONS: We explored the heritable biology of osteolysis at the whole genome level and identify several genetic loci that associate with susceptibility to osteolysis or with premature revision surgery. However, further studies are required to determine a causal association between the identified signals and osteolysis and their functional role in the disease. CLINICAL RELEVANCE: The identification of novel genetic risk loci for osteolysis enables new investigative avenues for clinical biomarker discovery and therapeutic intervention in this disease.
Assuntos
Artroplastia de Quadril/efeitos adversos , Artroplastia de Quadril/instrumentação , Loci Gênicos , Articulação do Quadril/cirurgia , Prótese de Quadril , Osteólise/genética , Falha de Prótese , Idoso , Distinções e Prêmios , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Articulação do Quadril/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Noruega , Osteólise/diagnóstico , Osteólise/fisiopatologia , Osteólise/cirurgia , Desenho de Prótese , Sistema de Registros , Reoperação , Fatores de Risco , Fatores de Tempo , Tempo para o Tratamento , Resultado do Tratamento , Reino UnidoRESUMO
BACKGROUND: Reverse total shoulder arthroplasty (RTSA) is now the most frequently performed form of shoulder arthroplasty. There is currently no consensus on recommended levels of activity and sport following RTSA. The aim of this review is to outline the current evidence and provide a guide for surgeons on what to advise their patients regarding activity level following RTSA. METHODS: A systematic review of the literature was performed using the Preferred Reporting for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The search was performed using the electronic databases PubMed and Medline. Included studies were of level 1 to 4 evidence in the English language evaluating complications and return to sport after RTSA. RESULTS: Eleven studies were selected and included a total of 621 patients (67% female) with a mean age of 73 years (range 22-92). All of the included patients participated in sports prior to RTSA. The rate of return to sport ranged from 60 to 86% and varied with the level of sport activity. Mean time to return to sport after surgery varied greatly between studies. CONCLUSIONS: Return to sport is tolerated following RTSA; however, studies are short to medium term only and although the reported complication rate is low, the studies did not include radiographic evaluation. Longer term studies with subgroup analysis evaluating common recreational activities after RTSA are required, particularly in the younger population, in order to establish clear post-operative guidelines.
RESUMO
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 (2007-11), 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.
RESUMO
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.