title: Bone deficits in parenteral nutrition-dependent infants and children with intestinal failure are attenuated when accounting for slower growth.
abstract: OBJECTIVE
  The aim of the present study was to determine whether bone mineral content (BMC) and density (BMD) of infants and children with parenteral nutrition (PN)-dependent intestinal failure (IF) is lower than healthy controls, and investigate potential causes of lower BMC and BMD.
  
  
  METHODS
  We performed a cross-sectional study comparing infants and children with PN-dependent IF with duos of age-, sex-, and race-matched controls. Lumbar spine BMC and BMD were measured by dual-energy x-ray absorptiometry, and serum cytokines, aluminum, insulin-like growth factor-1 (IGF-1), IGF-binding protein 3 (IGF-BP3), parathyroid hormone, 25-hydroxy vitamin D, and 1,25-dihydroxy vitamin D were measured. Generalized estimating equation models accounting for matching were used for comparisons.
  
  
  RESULTS
  BMC was 15% and BMD was 12% lower in IF participants than in controls (P ≤ 0.004). Group differences were attenuated to 3% and 7% and were not statistically significant (P = 0.40 and P = 0.07) when adjusted for length and weight; length- and weight-for-age were lower in IF than in control participants (12.5% vs 63%; 29.5% vs 54%, P ≤ 0.03). IF participants had higher serum aluminum (23 vs 7 μg/L, P < 0.0001), IGF-1 (97 vs 64 ng/mL, P = 0.04), and 25-hydroxy vitamin D concentrations (40 vs 30 ng/mL, P = 0.0005), and lower IGF-BP3 (1418 vs 1812 ng/mL, P < 0.0001) and parathyroid hormone concentrations (51 vs 98 pg/mL, P = 0.0002) than controls. There was no difference in serum cytokine concentrations (P ≥ 0.09).
  
  
  CONCLUSIONS
  Growth retardation is a significant problem for patients with PN-dependent IF. Additional investigation is needed to elucidate the cause and its effect on bone mass and density, especially the role of IGF-1 resistance and aluminum toxicity.
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH 45229, USA. slsimo@gwu.edu
authors.forename: Stephanie S
authors.initials: SS
authors.lastname: Appleman
authors.forename: Heidi J
authors.initials: HJ
authors.lastname: Kalkwarf
authors.forename: Alok
authors.initials: A
authors.lastname: Dwivedi
authors.forename: James E
authors.initials: JE
authors.lastname: Heubi
mesh_terms: D015652:25-Hydroxyvitamin D 2 / Q000097:blood / Q000378:metabolism; D000535:Aluminum / Q000009:adverse effects / Q000097:blood; D015519:Bone Density; D001846:Bone Development; D001847:Bone Diseases / Q000209:etiology* / Q000517:prevention & control; D002112:Calcifediol / Q000097:blood / Q000378:metabolism; D002648:Child; D002657:Child Development; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D005260:Female; D006130:Growth Disorders / Q000209:etiology* / Q000517:prevention & control; D006801:Humans; D007223:Infant; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000378:metabolism; D007410:Intestinal Diseases / Q000097:blood / Q000378:metabolism / Q000503:physiopathology* / Q000628:therapy; D007422:Intestines / Q000503:physiopathology*; D008297:Male; D010281:Parathyroid Hormone / Q000097:blood / Q000378:metabolism; D010288:Parenteral Nutrition / Q000009:adverse effects
chemical_list: C583557:IGF1 protein, human; C470125:PTH protein, human; D010281:Parathyroid Hormone; D015652:25-Hydroxyvitamin D 2; D007334:Insulin-Like Growth Factor I; D000535:Aluminum; D002112:Calcifediol