{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T14:54:35Z","timestamp":1791125675262,"version":"4.1.0"},"reference-count":20,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2004,10,28]],"date-time":"2004-10-28T00:00:00Z","timestamp":1098921600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pediatric Blood &amp; Cancer"],"published-print":{"date-parts":[[2005,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Osteonecrosis (ON) as a complication during treatment of acute lymphoblastic leukemia (ALL) has gained rising attention over the past decade. Corticosteroids, representing an essential element of antileukemic therapy, are known to induce ON, which in turn may cause significant morbidity. Due to spontaneous reporting of affected patients with ON, a group\u2010wide evaluation was performed to determine incidence, risk factors, and morbidity for ON.<\/jats:p><\/jats:sec><jats:sec><jats:title>Procedure<\/jats:title><jats:p>Patients were identified via spontaneous reporting to the study center and via questionnaire, addressing all 64 participating centers. We retrospectively analyzed 1,951 patients below 18 years of age who were treated according to trial ALL\u2010BFM 95 between 01.01.1996 and 30.06.2000.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Thirty\u2010one patients (14 male, 17 female) affected by ON were identified. The overall 5\u2010year cumulative incidence for ON is 1.8%. The incidence for patients &lt;10 years is 0.2%, whereas for patients \u226510 years it is 8.9% (<jats:italic>P<\/jats:italic>\u2009=\u20090.00) and 16.7% (<jats:italic>P<\/jats:italic>\u2009=\u20090.003) for patients \u226515 years. The majority (n\u2009=\u200920) showed ON in two or more joints, and the joints most commonly affected were knees (14 patients, 24 affected knees) and hips (11 patients, 20 affected joints). Thirteen out of 31 patients had to undergo surgery in the course of their disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Symptomatic ON is a rare event in patients treated with BFM\u2010type chemotherapy with an overall 5\u2010year cumulative incidence of 1.8%. The age group \u226510 years, and particularly adolescents \u226515 years have a significantly higher risk of developing ON. \u00a9 2004 Wiley\u2010Liss, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pbc.20244","type":"journal-article","created":{"date-parts":[[2004,11,7]],"date-time":"2004-11-07T22:54:43Z","timestamp":1099868083000},"page":"220-225","source":"Crossref","is-referenced-by-count":129,"title":["Osteonecrosis: A treatment related toxicity in childhood acute lymphoblastic leukemia (ALL)\u2014experiences from trial ALL\u2010BFM 95"],"prefix":"10.1002","volume":"44","author":[{"given":"Britta","family":"B\u00fcrger","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rita","family":"Beier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Zimmermann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f6rn D.","family":"Beck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfred","family":"Reiter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Schrappe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2004,10,28]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2000.18.18.3262"},{"key":"e_1_2_6_3_2","doi-asserted-by":"crossref","first-page":"3066","DOI":"10.1200\/JCO.2001.19.12.3066","article-title":"Bony morbidity in children treated for acute lymphoblastic leukemia","volume":"12","author":"Strauss AJ","year":"2001","journal-title":"J Clin Oncol"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(19900415)65:8<1717::AID-CNCR2820650809>3.0.CO;2-B"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-911X(199901)32:1<11::AID-MPO4>3.0.CO;2-F"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199205283262206"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-2001-12883"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1097\/00003086-199912000-00033"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.85.8.2907"},{"key":"e_1_2_6_10_2","first-page":"2166","article-title":"Apoptotic cell death in steroid induced osteonecrosis: An experimental study in rabbits","volume":"27","author":"Kabata T","year":"2000","journal-title":"J Rheumatol"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1097\/00003086-200103000-00025"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1053\/sarh.2002.33724b"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4615-4811-9_66"},{"key":"e_1_2_6_14_2","first-page":"3310","article-title":"Improved outcome in childhood acute lymphoblastic leukemia despite reduced use of anthracyclines and cranial radiotherapy: Results of trial ALL\u2010BFM 90","volume":"95","author":"Schrappe M","year":"2000","journal-title":"Blood"},{"key":"e_1_2_6_15_2","first-page":"163","volume-title":"The statistical analysis of failure time data","author":"Kalbfleisch JD","year":"1980"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1214\/aos\/1176350951"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.3109\/17453679209154813"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1136\/adc.82.5.385"},{"key":"e_1_2_6_19_2","first-page":"747","article-title":"Osteonecrosis: An emerging complication of intensive chemotherapy for childhood acute lymphoblastic leukemia","volume":"88","author":"Arico M","year":"2003","journal-title":"Hematologica"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2402139"},{"key":"e_1_2_6_21_2","first-page":"1459","volume-title":"The pharmacological basis of therapeutics","author":"Haynes RC","year":"1985"}],"container-title":["Pediatric Blood &amp; 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