title: Long-term inflammation and glucocorticoid therapy impair skeletal modeling during growth in childhood Crohn disease.
abstract: BACKGROUND
  Glucocorticoids and inflammation inhibit bone formation; however, the impact on skeletal modeling is unknown.
  
  
  OBJECTIVE
  The objectives of the study were to examine changes in bone mineral density (BMD) and cortical structure after Crohn disease (CD) diagnosis and identify associations with growth, glucocorticoids, and disease activity.
  
  
  METHODS
  This was a prospective cohort study among 76 CD participants, aged 5-21 years. Tibia quantitative computed tomography trabecular BMD and cortical dimensions were obtained at diagnosis and 6 and 12 and a median of 42 months later; 51 completed the final visit.
  
  
  RESULTS
  Sex, race, and age-specific Z-scores were generated for outcomes based on more than 650 reference participants, and cortical dimension Z-scores were further adjusted for tibia length. Generalized estimating equations were used to model changes in Z-scores.
  
  
  RESULTS
  Disease activity improved over the study interval (P < .001). Trabecular BMD Z-scores improved over the first 6 months; increases were associated with improved disease activity (P < .001), younger age (P = .005), and increases in vitamin D levels (P = .02). Greater increases in tibia length were associated with greater increases in cortical area Z-scores (P < .001). Greater glucocorticoid doses and disease activity were significantly associated with failure to accrue cortical area and were more pronounced with greater linear growth (interaction P < .05). Mean (±SD) trabecular BMD (-1.0 ± 1.21) and cortical area (-0.57 ± 1.10) Z-scores at the final visit were significantly reduced.
  
  
  CONCLUSIONS
  CD was associated with persistent deficits in trabecular BMD, although younger participants demonstrated a greater potential for recovery. In addition, greater linear growth was associated with a greater recovery of cortical dimensions, especially among participants with less glucocorticoid exposure and inflammation. These data suggest that younger age and concurrent growth provide a window of opportunity for skeletal recovery.
authors.affiliation: Department of Pediatrics, Children's Hospital of Eastern Ontario, Ontario, Canada K1H 8L6.
authors.forename: Anne
authors.initials: A
authors.lastname: Tsampalieros
authors.forename: Carol K L
authors.initials: CK
authors.lastname: Lam
authors.forename: Jenna C
authors.initials: JC
authors.lastname: Spencer
authors.forename: Meena
authors.initials: M
authors.lastname: Thayu
authors.forename: Justine
authors.initials: J
authors.lastname: Shults
authors.forename: Babette S
authors.initials: BS
authors.lastname: Zemel
authors.forename: Rita M
authors.initials: RM
authors.lastname: Herskovitz
authors.forename: Robert N
authors.initials: RN
authors.lastname: Baldassano
authors.forename: Mary B
authors.initials: MB
authors.lastname: Leonard
mesh_terms: D000293:Adolescent; D000328:Adult; D015519:Bone Density; D001846:Bone Development / Q000187:drug effects*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003424:Crohn Disease / Q000150:complications* / Q000188:drug therapy / Q000503:physiopathology; D005260:Female; D005938:Glucocorticoids / Q000009:adverse effects*; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D008297:Male; D011446:Prospective Studies; D013997:Time Factors
chemical_list: D005938:Glucocorticoids