title: Adipokines and C-reactive protein in relation to bone mineralization in pediatric nonalcoholic fatty liver disease.
abstract: OBJECTIVE
  To investigate bone mineral density (BMD) in obese children with and without nonalcoholic fatty liver disease (NAFLD); and the association between BMD and serum adipokines, and high-sensitivity C-reactive protein (HSCRP).
  
  
  METHODS
  A case-control study was performed. Cases were 44 obese children with NAFLD. The diagnosis of NAFLD was based on magnetic resonance imaging (MRI) with high hepatic fat fraction (≥ 5%). Other causes of chronic liver disease were ruled out. Controls were selected from obese children with normal levels of aminotransferases, and without MRI evidence of fatty liver as well as of other causes of chronic liver diseases. Controls were matched (1- to 1-basis) with the cases on age, gender, pubertal stage and as closely as possible on body mass index-SD score. All participants underwent clinical examination, laboratory tests, and whole body (WB) and lumbar spine (LS) BMD by dual energy X-ray absorptiometry. BMD Z-scores were calculated using race and gender specific LMS curves.
  
  
  RESULTS
  Obese children with NAFLD had a significantly lower LS BMD Z-score than those without NAFLD [mean, 0.55 (95%CI: 0.23-0.86) vs 1.29 (95%CI: 0.95-1.63); P < 0.01]. WB BMD Z-score was also decreased in obese children with NAFLD compared to obese children with no NAFLD, though borderline significance was observed [1.55 (95%CI: 1.23-1.87) vs 1.95 (95%CI: 1.67-2.10); P = 0.06]. Children with NAFLD had significantly higher HSCRP, lower adiponectin, but similar leptin levels. Thirty five of the 44 children with MRI-diagnosed NAFLD underwent liver biopsy. Among the children with biopsy-proven NAFLD, 20 (57%) had nonalcoholic steatohepatitis (NASH), while 15 (43%) no NASH. Compared to children without NASH, those with NASH had a significantly lower LS BMD Z-score [mean, 0.27 (95%CI: -0.17-0.71) vs 0.75 (95%CI: 0.13-1.39); P < 0.05] as well as a significantly lower WB BMD Z-score [1.38 (95%CI: 0.89-1.17) vs 1.93 (95%CI: 1.32-2.36); P < 0.05]. In multiple regression analysis, NASH (standardized β coefficient, -0.272; P < 0.01) and HSCRP (standardized β coefficient, -0.192; P < 0.05) were significantly and independently associated with LS BMD Z-score. Similar results were obtained when NAFLD (instead of NASH) was included in the model. WB BMD Z-scores were significantly and independently associated with NASH (standardized β coefficient, -0.248; P < 0.05) and fat mass (standardized β coefficient, -0.224; P < 0.05).
  
  
  CONCLUSIONS
  This study reveals that NAFLD is associated with low BMD in obese children, and that systemic, low-grade inflammation may accelerate loss of bone mass in patients with NAFLD.
authors.affiliation: Department of Pediatrics, Sapienza University of Rome, 00161 Rome, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Pacifico
authors.forename: Mario
authors.initials: M
authors.lastname: Bezzi
authors.forename: Concetta Valentina
authors.initials: CV
authors.lastname: Lombardo
authors.forename: Sara
authors.initials: S
authors.lastname: Romaggioli
authors.forename: Flavia
authors.initials: F
authors.lastname: Ferraro
authors.forename: Stefano
authors.initials: S
authors.lastname: Bascetta
authors.forename: Claudio
authors.initials: C
authors.lastname: Chiesa
mesh_terms: D015502:Absorptiometry, Photon; D054392:Adipokines / Q000097:blood*; D052242:Adiponectin / Q000097:blood; D000293:Adolescent; D001706:Biopsy; D015519:Bone Density / Q000502:physiology*; D002097:C-Reactive Protein / Q000378:metabolism*; D016022:Case-Control Studies; D002648:Child; D015897:Comorbidity; D005234:Fatty Liver / Q000097:blood* / Q000453:epidemiology / Q000503:physiopathology*; D005260:Female; D006801:Humans; D020738:Leptin / Q000097:blood; D008099:Liver / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D065626:Non-alcoholic Fatty Liver Disease; D009765:Obesity / Q000097:blood / Q000453:epidemiology / Q000503:physiopathology
chemical_list: D054392:Adipokines; D052242:Adiponectin; D020738:Leptin; D002097:C-Reactive Protein
keywords: Adipokines; Bone mineralization; C-reactive protein; Children; Dual energy X-ray absorptiometry; Nonalcoholic fatty liver disease