{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T01:01:46Z","timestamp":1777942906916,"version":"3.51.4"},"reference-count":38,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T00:00:00Z","timestamp":1774915200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T00:00:00Z","timestamp":1774915200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Blood &amp;amp; Cancer"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Osteonecrosis (ON) is a debilitating complication of acute lymphoblastic leukemia (ALL) therapy. While numerous studies have explored its incidence and associated risk factors, investigations using large\u2010scale cohorts remain important to characterize ON across heterogeneous populations. Objectives were to describe the incidence and risk factors of ON among Canadian pediatric patients with ALL.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>This nationwide retrospective cohort study included children &lt;19 years diagnosed with de novo ALL between 2001 and 2021 from the Cancer in Young People\u2010Canada registry. The primary outcome was time to serious ON, defined as the time between ALL diagnosis and ON grade \u2265 3 as per CTCAE. Cumulative incidence was estimated using competing risk analysis, and risk factors were evaluated using Cox proportional hazard regression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Result<\/jats:title>\n                    <jats:p>Among 2514 patients, 41 were diagnosed with serious ON, yielding a 5\u2010year cumulative incidence of 1.73 \u00b1 0.27%. Age \u226510 years, female sex, T\u2010cell immunophenotype, high\u2010risk ALL, corticosteroid type (prednisone vs. dexamethasone or combined), and hematopoietic stem cell transplant (HSCT) were significantly associated with serious ON in univariate analysis, while age \u226510 years (adjusted hazard ratio [aHR] = 7.40, 95% confidence interval [CI] = 3.29\u201316.69) and female sex (aHR = 2.69, 95% CI = 1.42\u20135.09) remained independently associated with serious ON in multivariable analysis. Asparaginase formulation, race, obesity, and thrombotic events were not associated with serious ON.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Nearly 2% of children with ALL developed serious ON. Children older than 10 years and females were at the highest risk. Understanding these risk factors is crucial for identifying high\u2010risk patients, though optimal preventive interventions remain to be established.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/1545-5017.70271","type":"journal-article","created":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T10:39:09Z","timestamp":1774953549000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Incidence and Risk Factors of Serious Osteonecrosis in Pediatric Acute Lymphoblastic Leukemia: A\u00a0CYP\u2010C Population\u2010Based Study"],"prefix":"10.1002","volume":"73","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-4359-743X","authenticated-orcid":false,"given":"No\u00e9mie","family":"de Villiers","sequence":"first","affiliation":[{"name":"Faculty of Medicine Universit\u00e9 Laval  Quebec City Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chantal","family":"\u00c9thier","sequence":"additional","affiliation":[{"name":"Centre de Recherche du CHU de Qu\u00e9bec\u2014Universit\u00e9 Laval  Quebec City Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caroline","family":"Laverdi\u00e8re","sequence":"additional","affiliation":[{"name":"Department of Pediatrics CHU Sainte\u2010Justine\u2014Universit\u00e9 de Montr\u00e9al  Montreal Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nathalie","family":"Alos","sequence":"additional","affiliation":[{"name":"Department of Pediatrics CHU Sainte\u2010Justine\u2014Universit\u00e9 de Montr\u00e9al  Montreal Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8712-6233","authenticated-orcid":false,"given":"Thai Hoa","family":"Tran","sequence":"additional","affiliation":[{"name":"Department of Pediatrics CHU Sainte\u2010Justine\u2014Universit\u00e9 de Montr\u00e9al  Montreal Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marie\u2010Claude","family":"Pelland\u2010Marcotte","sequence":"additional","affiliation":[{"name":"Centre de Recherche du CHU de Qu\u00e9bec\u2014Universit\u00e9 Laval  Quebec City Canada"},{"name":"Department of Pediatrics CHU de Qu\u00e9bec\u2014Centre M\u00e8re\u2010Enfant Soleil  Quebec City Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,3,31]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1400972"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3026(21)00136-8"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1182\/asheducation-2014.1.190"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-10-117150"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejcped.2023.100121"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2016.147595"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.5762"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjpo-2017-000122"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0151433"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.18093"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375\u2010023\u201002099\u20101"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-10-311969"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2006.06.2539"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2012.081265"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1097\/HS9.0000000000000544"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.25553"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm11092489"},{"key":"e_1_2_10_19_1","unstructured":"U.S. National Cancer Institute \"Cancer Therapy Evaluation Program Common Terminology Criteria for Adverse Events (CTCAE) v5.0.\" (2017):100."},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V120.21.665.665"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2011.37.3217"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.27300"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.15511"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2010.03.008"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(12)70274-7"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2013.095562"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2011.84"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.12956"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0033-1358723"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.29033"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0216328"},{"key":"e_1_2_10_32_1","unstructured":"P.Miettunen C.Stephenson andS.Haider \u201cUse of Intravenous Pamidronate in Pediatric Leukemia Patients with Osteonecrosis Results in Reduced Pain and May Halt Osteonecrosis Progression \u201dAbstract presented at the 2020 Pediatric Rheumatology Symposium. American College of Rheumatology72(suppl4). (2020)."},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1200\/JGO.17.00083"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.29183"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41408-025-01239-3"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.30968"},{"key":"e_1_2_10_37_1","first-page":"2095","article-title":"Fenofibrate Reduces Osteonecrosis Without Affecting Antileukemic Efficacy in Dexamethasone\u2010Treated Mice","volume":"106","author":"Payton M. A.","year":"2021","journal-title":"Haematologica"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.30683"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1097\/BPO.0000000000002919"}],"container-title":["Pediatric Blood &amp; Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/1545-5017.70271","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/1545-5017.70271","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/1545-5017.70271","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T07:10:21Z","timestamp":1777705821000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/1545-5017.70271"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,31]]},"references-count":38,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,6]]}},"alternative-id":["10.1002\/1545-5017.70271"],"URL":"https:\/\/doi.org\/10.1002\/1545-5017.70271","archive":["Portico"],"relation":{},"ISSN":["1545-5009","1545-5017"],"issn-type":[{"value":"1545-5009","type":"print"},{"value":"1545-5017","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,31]]},"assertion":[{"value":"2025-11-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-08","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-31","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70271"}}