title: Advanced bone age and hyperinsulinemia in overweight and obese children.
abstract: OBJECTIVE
  In obese children, bone age (BA) tends to significantly exceed chronological age (CA). In vitro studies in mice suggest that insulin may directly modulate skeletal growth. We investigated whether there is an association between fasting insulin and BA maturation in obese children.
  
  
  METHODS
  The study cohort comprised 74 overweight and obese children ages 4 to 13 years. BA divided by CA was used as an index for bone advancement. Participants were classified into tertiles based on their BA:CA ratio. Advanced BA maturation was defined as the third tertile, with BA:CA > 1.21. Components of the metabolic syndrome, including fasting insulin, fasting glucose, triglycerides, and high-density lipoprotein (HDL) levels, were measured.
  
  
  RESULTS
  Children with advanced BA were significantly younger, had a higher body mass index (BMI)-Z score (BMI-Z), and were taller than children with bone advancement in the lower tertiles. Females had a 4.7-fold increased risk for advanced BA compared with males (95% confidence interval [CI], 1.29-17.1; P = .02). Children with a BMI-Z ≥ 1.96 and fasting insulin ≤ 30 μU/L had a 3.6-fold increased risk of advanced BA (95% CI, 1.00-12.8; P = 0.05). Moreover, hyperinsulinemia (fasting insulin > 30 μU/L) was associated with a 6.8-fold increased risk for advanced BA, independent of the degree of obesity (95% CI, 1.45-32.1; P = .01).
  
  
  CONCLUSIONS
  Marked hyperinsulinemia is associated with advanced BA in obese children. Insulin appears to modulate skeletal growth in humans.
authors.affiliation: Pediatric Endocrinology and Diabetes Unit, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel Hashomer, Israel Sackler School of Medicine, Tel-Aviv University, Israel.
authors.forename: Orit
authors.initials: O
authors.lastname: Pinhas-Hamiel
authors.affiliation: Pediatric Endocrinology and Diabetes Unit, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel Hashomer, Israel.
authors.forename: Doreen
authors.initials: D
authors.lastname: Benary
authors.affiliation: Pediatric Endocrinology and Diabetes Unit, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel Hashomer, Israel Sackler School of Medicine, Tel-Aviv University, Israel.
authors.forename: Kineret
authors.initials: K
authors.lastname: Mazor-Aronovich
authors.affiliation: Pediatric Endocrinology and Diabetes Unit, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel Hashomer, Israel Sackler School of Medicine, Tel-Aviv University, Israel.
authors.forename: Michal
authors.initials: M
authors.lastname: Ben-Ami
authors.affiliation: Pediatric Endocrinology and Diabetes Unit, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel Hashomer, Israel Sackler School of Medicine, Tel-Aviv University, Israel.
authors.forename: Yael
authors.initials: Y
authors.lastname: Levy-Shraga
authors.affiliation: Women and Children's Health Research Unit, Gertner Institute.
authors.forename: Valentina
authors.initials: V
authors.lastname: Boyko
authors.affiliation: Pediatric Endocrinology and Diabetes Unit, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel Hashomer, Israel Sackler School of Medicine, Tel-Aviv University, Israel.
authors.forename: Dalit
authors.initials: D
authors.lastname: Modan-Moses
authors.affiliation: Sackler School of Medicine, Tel-Aviv University, Israel Women and Children's Health Research Unit, Gertner Institute.
authors.forename: Liat
authors.initials: L
authors.lastname: Lerner-Geva
mesh_terms: D000293:Adolescent; D000365:Age Determination by Skeleton; D015992:Body Mass Index; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D006946:Hyperinsulinism / Q000503:physiopathology*; D008297:Male; D009765:Obesity / Q000503:physiopathology*; D050177:Overweight / Q000503:physiopathology*