title: Aggravated bone density decline following symptomatic osteonecrosis in children with acute lymphoblastic leukemia.
abstract: Osteonecrosis and decline of bone density are serious side effects during and after treatment of childhood acute lymphoblastic leukemia. It is unknown whether osteonecrosis and low bone density occur together in the same patients, or whether these two osteogenic side-effects can mutually influence each other's development. Bone density and the incidence of symptomatic osteonecrosis were prospectively assessed in a national cohort of 466 patients with acute lymphoblastic leukemia (4-18 years of age) who were treated according to the dexamethasone-based Dutch Child Oncology Group-ALL9 protocol. Bone mineral density of the lumbar spine (BMDLS) (n=466) and of the total body (BMDTB) (n=106) was measured by dual X-ray absorptiometry. Bone density was expressed as age- and gender-matched standard deviation scores. Thirty patients (6.4%) suffered from symptomatic osteonecrosis. At baseline, BMDLS and BMDTB did not differ between patients who did or did not develop osteonecrosis. At cessation of treatment, patients with osteonecrosis had lower mean BMDLS and BMDTB than patients without osteonecrosis (respectively, with osteonecrosis: -2.16 versus without osteonecrosis: -1.21, P<0.01 and with osteonecrosis: -1.73 versus without osteonecrosis: -0.57, P<0.01). Multivariate linear models showed that patients with osteonecrosis had steeper BMDLS and BMDTB declines during follow-up than patients without osteonecrosis (interaction group time, P<0.01 and P<0.01). We conclude that bone density status at the diagnosis of acute lymphoblastic leukemia does not seem to influence the occurrence of symptomatic osteonecrosis. Bone density declines from the time that osteonecrosis is diagnosed; this suggests that the already existing decrease in bone density during acute lymphoblastic leukemia therapy is further aggravated by factors such as restriction of weight-bearing activities and destruction of bone architecture due to osteonecrosis. Osteonecrosis can, therefore, be considered a risk factor for low bone density in children with acute lymphoblastic leukemia.
authors.affiliation: Department of Pediatric Oncology/ Hematology, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands Princess Maxima Center, Utrecht, The Netherlands.
authors.forename: Marissa A H
authors.initials: MA
authors.lastname: den Hoed
authors.affiliation: Department of Pediatric Oncology/ Hematology, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands Princess Maxima Center, Utrecht, The Netherlands.
authors.forename: Saskia M F
authors.initials: SM
authors.lastname: Pluijm
authors.affiliation: Department of Pediatric Oncology/ Hematology, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands.
authors.forename: Mariël L
authors.initials: ML
authors.lastname: te Winkel
authors.affiliation: Dutch Childhood Oncology Group, The Hague, The Netherlands.
authors.forename: Hester A
authors.initials: HA
authors.lastname: de Groot-Kruseman
authors.affiliation: Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Utrecht, The Netherlands.
authors.forename: Martha
authors.initials: M
authors.lastname: Fiocco
authors.affiliation: Department of Pediatric Hemato-Oncology, Radboud University Medical Center Nijmegen, Utrecht, The Netherlands.
authors.forename: Peter
authors.initials: P
authors.lastname: Hoogerbrugge
authors.affiliation: Dutch Childhood Oncology Group, The Hague, The Netherlands Beatrix Children's Hospital, University of Groningen, Utrecht, The Netherlands.
authors.forename: Jan A
authors.initials: JA
authors.lastname: Leeuw
authors.affiliation: Dutch Childhood Oncology Group, The Hague, The Netherlands University Medical Center, Utrecht, The Netherlands.
authors.forename: Marrie C A
authors.initials: MC
authors.lastname: Bruin
authors.affiliation: Department of Pediatric Oncology/ Hematology, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands.
authors.forename: Inge M
authors.initials: IM
authors.lastname: van der Sluis
authors.affiliation: Dutch Childhood Oncology Group, The Hague, The Netherlands Leiden University Medical Center, Utrecht, The Netherlands.
authors.forename: Dorien
authors.initials: D
authors.lastname: Bresters
authors.affiliation: Department of Radiology, University Medical Center, Utrecht, The Netherlands.
authors.forename: Maarten H
authors.initials: MH
authors.lastname: Lequin
authors.affiliation: Vrije Universiteit Medical Center, Amsterdam, The Netherlands.
authors.forename: Jan C
authors.initials: JC
authors.lastname: Roos
authors.affiliation: Dutch Childhood Oncology Group, The Hague, The Netherlands Vrije Universiteit Medical Center, Amsterdam, The Netherlands.
authors.forename: Anjo J P
authors.initials: AJ
authors.lastname: Veerman
authors.affiliation: Princess Maxima Center, Utrecht, The Netherlands.
authors.forename: Rob
authors.initials: R
authors.lastname: Pieters
authors.affiliation: Dutch Childhood Oncology Group, The Hague, The Netherlands Princess Maxima Center, Utrecht, The Netherlands m.m.vandenheuvel-eibrink@prinsesmaximacentrum.nl.
authors.forename: Marry M
authors.initials: MM
authors.lastname: van den Heuvel-Eibrink
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000037:antagonists & inhibitors; D015519:Bone Density / Q000187:drug effects*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D008297:Male; D010020:Osteonecrosis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011446:Prospective Studies