title: Longitudinal assessment of bone density and structure in childhood survivors of acute lymphoblastic leukemia without cranial radiation.
abstract: OBJECTIVE
  Children with acute lymphoblastic leukemia (ALL) are at risk for impaired bone accrual. This peripheral quantitative computed tomography study assessed changes in bone mineral density (BMD) and structure after completion of ALL treatment.
  
  
  METHODS
  Fifty ALL participants, ages 5-22 yr, were enrolled within 2 yr (median 0.8 yr) after completing ALL therapy. Tibia peripheral quantitative computed tomography scans were performed at enrollment and 12 months later. Age-, sex-, and race-specific Z-scores for trabecular BMD (TrabBMD), cortical BMD (CortBMD), and cortical area (CortArea) were generated based on more than 650 reference participants. Multivariable linear regression models examined determinants of changes in Z-scores.
  
  
  RESULTS
  At enrollment, mean TrabBMD (-1.03±1.34) and CortBMD (-0.84±1.05) Z-scores were low (both P<0.001) compared with reference participants. TrabBMD and CortBMD Z-scores increased to -0.58±1.41 and -0.51±0.91 over 1 yr, respectively (both P<0.001). Changes in cortical outcomes varied according to the interval since completion of therapy. Among those enrolled less than 6 months after therapy, CortArea Z-scores increased and CortBMD Z-scores decreased (both P<0.01). Among those enrolled 6 months or more after therapy, CortArea Z-scores did not change and CortBMD Z-scores increased (P<0.01). Changes in CortArea and CortBMD Z-scores were inversely associated (r=-0.32, P<0.001). Cumulative glucocorticoid exposure, leukemia risk status, and antimetabolite chemotherapy were not associated with outcomes.
  
  
  CONCLUSIONS
  TrabBMD was low after completion of ALL therapy and improved significantly. Early increases in cortical dimensions were associated with declines in CortBMD; however, participants further from ALL therapy demonstrated stable cortical dimensions and increases in CortBMD, potentially reflecting the time necessary to mineralize newly formed bone.
authors.affiliation: Department of Pediatrics, The Children's Hospital of Philadelphia, and Department of Biostatistics and Epidemiology, The University of Pennsylvania Perelman School of Medicine, 3535 Market Street, Philadelphia, Pennsylvania 19104, USA. moab@email.chop.edu
authors.forename: Sogol
authors.initials: S
authors.lastname: Mostoufi-Moab
authors.forename: Jill
authors.initials: J
authors.lastname: Brodsky
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Isaacoff
authors.forename: Anne
authors.initials: A
authors.lastname: Tsampalieros
authors.forename: Jill P
authors.initials: JP
authors.lastname: Ginsberg
authors.forename: Babette
authors.initials: B
authors.lastname: Zemel
authors.forename: Justine
authors.initials: J
authors.lastname: Shults
authors.forename: Mary B
authors.initials: MB
authors.lastname: Leonard
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000502:physiology; D000293:Adolescent; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001827:Body Height / Q000187:drug effects / Q000502:physiology; D015519:Bone Density / Q000187:drug effects* / Q000502:physiology*; D001842:Bone and Bones / Q000187:drug effects / Q000502:physiology; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D050723:Fractures, Bone / Q000453:epidemiology / Q000503:physiopathology; D006801:Humans; D015994:Incidence; D008137:Longitudinal Studies; D008297:Male; D015999:Multivariate Analysis; D018482:Muscle, Skeletal / Q000187:drug effects / Q000502:physiology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000453:epidemiology / Q000503:physiopathology*; D017741:Survivors / Q000706:statistics & numerical data; D014807:Vitamin D / Q000008:administration & dosage; D014815:Vitamins / Q000008:administration & dosage; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D014815:Vitamins; D014807:Vitamin D