{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T13:06:32Z","timestamp":1762866392091},"reference-count":21,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2014,3,27]],"date-time":"2014-03-27T00:00:00Z","timestamp":1395878400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2014,7]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Bisphosphonates are recommended in patients with osteolytic lesions secondary to multiple myeloma. We report on the safety of bisphosphonate therapy with long\u2010term follow\u2010up in the Medical Research Council Myeloma <jats:styled-content style=\"fixed-case\">IX<\/jats:styled-content> study. Patients with newly diagnosed multiple myeloma were randomised to zoledronic acid (<jats:styled-content style=\"fixed-case\">ZOL<\/jats:styled-content>; 4\u00a0mg intravenously every 21\u201328\u00a0d) or clodronate (<jats:styled-content style=\"fixed-case\">CLO<\/jats:styled-content>; 1600\u00a0mg\/d orally) plus chemotherapy. Among 1960 patients (5\u00b79\u2010year median follow\u2010up), both bisphosphonates were well tolerated. Acute renal failure events were similar between groups (<jats:styled-content style=\"fixed-case\">ZOL<\/jats:styled-content> 5\u00b72% vs. <jats:styled-content style=\"fixed-case\">CLO<\/jats:styled-content> 5\u00b78% at 2\u00a0years; incidence plateaued thereafter). The overall incidence of confirmed osteonecrosis of the jaw (<jats:styled-content style=\"fixed-case\">ONJ<\/jats:styled-content>) was low, but higher with <jats:styled-content style=\"fixed-case\">ZOL<\/jats:styled-content> (<jats:styled-content style=\"fixed-case\">ZOL<\/jats:styled-content> 3\u00b77% vs. <jats:styled-content style=\"fixed-case\">CLO<\/jats:styled-content> 0\u00b75%; <jats:italic>P\u00a0&lt;\u00a0<\/jats:italic>0\u00b70001). <jats:styled-content style=\"fixed-case\">ONJ<\/jats:styled-content> events were generally low grade and most occurred between 8 and 30\u00a0months (median time to <jats:styled-content style=\"fixed-case\">ONJ<\/jats:styled-content>, 23\u00b77\u00a0months). Among 10 patients with <jats:styled-content style=\"fixed-case\">ONJ<\/jats:styled-content> recovery data, four patients in the <jats:styled-content style=\"fixed-case\">ZOL<\/jats:styled-content> group completely recovered, two patients improved, and three patients experienced no improvement; one <jats:styled-content style=\"fixed-case\">CLO<\/jats:styled-content> patient experienced no improvement. Dental surgery or trauma preceded <jats:styled-content style=\"fixed-case\">ONJ<\/jats:styled-content> in six <jats:styled-content style=\"fixed-case\">ZOL<\/jats:styled-content> patients. The incidence of renal adverse events was similar for <jats:styled-content style=\"fixed-case\">ZOL<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">CLO<\/jats:styled-content>. <jats:styled-content style=\"fixed-case\">ONJ<\/jats:styled-content> incidence remained low and was lower with <jats:styled-content style=\"fixed-case\">CLO<\/jats:styled-content> compared to <jats:styled-content style=\"fixed-case\">ZOL<\/jats:styled-content>. We have seen no further <jats:styled-content style=\"fixed-case\">ONJ<\/jats:styled-content> cases to date.<\/jats:p>","DOI":"10.1111\/bjh.12861","type":"journal-article","created":{"date-parts":[[2014,3,27]],"date-time":"2014-03-27T10:06:34Z","timestamp":1395914794000},"page":"109-117","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Osteonecrosis of the jaw and renal safety in patients with newly diagnosed multiple myeloma: Medical Research Council Myeloma <scp>IX<\/scp> Study results"],"prefix":"10.1111","volume":"166","author":[{"given":"Graham H.","family":"Jackson","sequence":"first","affiliation":[{"name":"University of Newcastle Newcastle\u2010upon\u2010Tyne UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gareth J.","family":"Morgan","sequence":"additional","affiliation":[{"name":"Institute of Cancer Research Royal Marsden Hospital London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Faith E.","family":"Davies","sequence":"additional","affiliation":[{"name":"Institute of Cancer Research Royal Marsden Hospital London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ping","family":"Wu","sequence":"additional","affiliation":[{"name":"Institute of Cancer Research Royal Marsden Hospital London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Walter M.","family":"Gregory","sequence":"additional","affiliation":[{"name":"Clinical Trials Research Unit University of Leeds Leeds UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sue E.","family":"Bell","sequence":"additional","affiliation":[{"name":"Clinical Trials Research Unit University of Leeds Leeds UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander J.","family":"Szubert","sequence":"additional","affiliation":[{"name":"Clinical Trials Research Unit University of Leeds Leeds UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nuria","family":"Navarro Coy","sequence":"additional","affiliation":[{"name":"Clinical Trials Research Unit University of Leeds Leeds UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark T.","family":"Drayson","sequence":"additional","affiliation":[{"name":"University of Birmingham Birmingham UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roger G.","family":"Owen","sequence":"additional","affiliation":[{"name":"St James's University Hospital Leeds UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sylvia","family":"Feyler","sequence":"additional","affiliation":[{"name":"Calderdale and Huddersfield NHS Trust Huddersfield UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew J.","family":"Ashcroft","sequence":"additional","affiliation":[{"name":"Mid Yorkshire Hospitals NHS Trust Wakefield UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fiona M.","family":"Ross","sequence":"additional","affiliation":[{"name":"Wessex Regional Genetics Laboratory University of Southampton Salisbury UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer","family":"Byrne","sequence":"additional","affiliation":[{"name":"Nottingham University Hospitals Nottingham UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huw","family":"Roddie","sequence":"additional","affiliation":[{"name":"Western General Hospital Edinburgh UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudius","family":"Rudin","sequence":"additional","affiliation":[{"name":"Royal Devon and Exeter Hospital Exeter UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kevin D.","family":"Boyd","sequence":"additional","affiliation":[{"name":"Institute of Cancer Research Royal Marsden Hospital London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wendy L.","family":"Osborne","sequence":"additional","affiliation":[{"name":"Freeman Hospital Newcastle Newcastle\u2010upon\u2010Tyne UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gordon","family":"Cook","sequence":"additional","affiliation":[{"name":"St James's University Hospital Leeds UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. 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