title: Risk factors and surveillance for reduced bone mineral density in pediatric cancer survivors.
abstract: BACKGROUND
  Pediatric cancer survivors are at increased risk of developing low bone mineral density (BMD) due to cancer treatment. This study assessed the yield of screening for low BMD in pediatric-aged cancer survivors as per the Children's Oncology Group Long-Term Follow-Up (COG-LTFU) Guidelines, which recommend screening survivors who received steroids, methotrexate, or hematopoietic cell transplant (HCT).
  
  
  METHODS
  This is a retrospective cohort study of 475 pediatric blood cancer and noncentral nervous system solid tumor survivors screened for low BMD with dual-energy X-ray absorptiometry (DXA) as per the COG-LTFU Guidelines from 2003 to 2010. Risk factors for low BMD (DXA Z-score ≤-2) were evaluated by univariate and multivariate analysis.
  
  
  RESULTS
  The mean DXA Z-score was -0.1 for both whole body and lumbar spine measurements. Among at-risk survivors, 8.2% (39/475) had low BMD. Multivariate analysis of survivors with low BMD showed significant association with male gender (odds ratio [OR] 3.4, 95% confidence interval [CI], 1.3-9.0), exposure to total body irradiation (TBI), cranial, or craniospinal radiation (OR 5.2, 95% CI, 1.8-14.9), and gonadal dysfunction (OR 4.3, 95% CI, 1.4-13.0). Methotrexate exposure was not significantly associated with low BMD. Survivors receiving HCT had a reduced risk of low BMD (OR 0.2, 95% CI, 0.1-0.9).
  
  
  CONCLUSIONS
  The highest risk factors for low BMD were male gender, exposure to TBI, cranial, or craniospinal radiation, and gonadal dysfunction. Survivors receiving methotrexate or HCT therapy have the lowest risk for low BMD among those screened. Future studies should investigate risk of low BMD for survivors receiving HCT without radiation exposure.
authors.affiliation: Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Atlanta, Georgia.|Department of Pediatrics, Emory University, Atlanta, Georgia.
authors.forename: David A
authors.initials: DA
authors.lastname: Siegel
authors.affiliation: Department of Community Health and Preventive Medicine, Morehouse School of Medicine, Atlanta, Georgia.
authors.forename: Mechelle
authors.initials: M
authors.lastname: Claridy
authors.affiliation: Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Atlanta, Georgia.|Department of Pediatrics, Emory University, Atlanta, Georgia.
authors.forename: Ann
authors.initials: A
authors.lastname: Mertens
authors.affiliation: Center for Outcomes Research and Evaluation, Yale New Haven Hospital, New Haven, Connecticut.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: George
authors.affiliation: IS&T, Business Intelligence, Children's Healthcare of Atlanta, Atlanta, Georgia.
authors.forename: Kristen
authors.initials: K
authors.lastname: Vangile
authors.affiliation: Department of Pediatrics, Emory University, Atlanta, Georgia.|Department of Radiology and Imaging Sciences, Children's Healthcare of Atlanta, Atlanta, Georgia.
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Simoneaux
authors.affiliation: Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Atlanta, Georgia.|Department of Pediatrics, Emory University, Atlanta, Georgia.
authors.forename: Lillian R
authors.initials: LR
authors.lastname: Meacham
authors.affiliation: Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Atlanta, Georgia.|Department of Pediatrics, Emory University, Atlanta, Georgia.
authors.forename: Karen
authors.initials: K
authors.lastname: Wasilewski-Masker
mesh_terms: D015502:Absorptiometry, Photon; D000293:Adolescent; D015519:Bone Density; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008403:Mass Screening; D015999:Multivariate Analysis; D009369:Neoplasms / Q000628:therapy*; D011878:Radiotherapy / Q000009:adverse effects; D012189:Retrospective Studies; D017741:Survivors
keywords: bone mineral density; late effects; pediatric cancer survivors