{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:47:59Z","timestamp":1786978079944,"version":"build-2736575974"},"reference-count":37,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2014,11,16]],"date-time":"2014-11-16T00:00:00Z","timestamp":1416096000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Internal departmental funding"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Orthopaedic Research"],"published-print":{"date-parts":[[2015,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>\n                      Wear particle\u2010induced 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\u2010stage case\u2010control 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\u2010SNP tagging using a 2\u2010stage association analysis approach. In the discovery cohort four SNPs within RANK, and one each within\n                      <jats:italic>KREMEN2<\/jats:italic>\n                      ,\n                      <jats:italic>OPG<\/jats:italic>\n                      ,\n                      <jats:italic>SFRP1<\/jats:italic>\n                      , and\n                      <jats:italic>TIRAP<\/jats:italic>\n                      (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05) were associated with osteolysis susceptibility. Two SNPs within\n                      <jats:italic>LRP6<\/jats:italic>\n                      , and one each within\n                      <jats:italic>LRP5<\/jats:italic>\n                      ,\n                      <jats:italic>NOD2, SOST, SQSTM1, TIRAP<\/jats:italic>\n                      , and\n                      <jats:italic>TRAM<\/jats:italic>\n                      associated with time to implant failure (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05). Meta\u2010analysis of the two cohorts identified four SNPs within\n                      <jats:italic>RANK<\/jats:italic>\n                      , and one each within\n                      <jats:italic>KREMEN2<\/jats:italic>\n                      , OPG,\n                      <jats:italic>SFRP1<\/jats:italic>\n                      , and\n                      <jats:italic>TIRAP<\/jats:italic>\n                      associated with osteolysis susceptibility (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05). Genetic variation within inflammatory signaling and bone turnover pathways may play a role in susceptibility to osteolysis. \u00a9 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:193\u2013198, 2015.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jor.22755","type":"journal-article","created":{"date-parts":[[2014,11,16]],"date-time":"2014-11-16T23:53:04Z","timestamp":1416181984000},"page":"193-198","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Genetic variation in inflammatory and bone turnover pathways and risk of osteolytic responses to prosthetic materials"],"prefix":"10.1002","volume":"33","author":[{"given":"Scott J.","family":"MacInnes","sequence":"first","affiliation":[{"name":"Department of Human Metabolism University of Sheffield Sheffield United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena Del","family":"Vescovo","sequence":"additional","affiliation":[{"name":"Department of Human Metabolism University of Sheffield Sheffield United 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