title: Osteoprotegerin serum levels in children with type 1 diabetes: a potential modulating role in bone status.
abstract: OBJECTIVE
  Children and adolescents with type 1 (insulin-dependent) diabetes mellitus (T1DM) show several impairment of bone metabolism and structure, resulting in a higher risk of decreased bone mass and its related complications later in life. Alterations of the nuclear factor-kappaB ligand (RANKL)/osteoprotegerin (OPG) system have been implicated in several metabolic bone diseases characterized by increased osteoclast differentiation and activation and enhanced bone resorption.
  
  
  METHODS
  We aimed to assess OPG levels and to investigate the possible relation between OPG levels, bone status and glycemic control in a group of prepubertal children with T1DM without microvascular complications.
  
  
  METHODS
  Twenty-six prepubertal T1DM children (median age 9.9 years, range 4.1-13.1 years) were studied. In all patients, serum OPG, hemoglobin (Hb)A1c, parathyroid hormone (PTH) and 25-dihy-droxyvitamin D (25-D) levels were evaluated. Bone quality was determined by measuring the attenuation of ultrasound waves by bone (broadband ultrasound attenuation (BUA)) at the calcaneal site. The data were compared with those of a group of 45 age-, sex-and body-size-matched healthy children.
  
  
  RESULTS
  Children with T1DM showed a reduced Z-score BUA in comparison with the control group (Student's t-test, P < 0.0001). Plasma OPG levels were significantly higher in diabetic children than in controls (Student's t-test, P < 0.0001). In T1DM children, Z-score BUA values displayed a significant correlation with OPG (Student's t-test, r = -0.62; P = 0.001), and HbA1c (r = -0.59; P = 0.007). OPG levels were significantly correlated with HbA1c (r = 0.56; P = 0.008). In a multiple regression analysis including age, duration of diabetes, physical activity, calcium intake, mean HbA1c and Z-score BUA, only HbA1c significantly predicted serum OPG levels (beta 0.67; P = 0.003).
  
  
  CONCLUSIONS
  Prepubertal children with T1DM have a significant increase of OPG levels. OPG serum concentrations are correlated to calcaneal BUA and HbA1c values. OPG could be a new marker of reduced bone mass in children with T1DM.
authors.affiliation: Department of Paediatrics, A Meyer Children's Hospital,Via Luca Giordano 13, 50132 Florence, Italy.
authors.forename: Fiorella
authors.initials: F
authors.lastname: Galluzzi
authors.forename: Stefano
authors.initials: S
authors.lastname: Stagi
authors.forename: Roberto
authors.initials: R
authors.lastname: Salti
authors.forename: Sonia
authors.initials: S
authors.lastname: Toni
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Piscitelli
authors.forename: Gabriele
authors.initials: G
authors.lastname: Simonini
authors.forename: Fernanda
authors.initials: F
authors.lastname: Falcini
authors.forename: Francesco
authors.initials: F
authors.lastname: Chiarelli
mesh_terms: D000293:Adolescent; D015519:Bone Density / Q000187:drug effects; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000097:blood*; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006023:Glycoproteins / Q000097:blood*; D006801:Humans; D008297:Male; D053244:Osteoprotegerin; D018160:Receptors, Cytoplasmic and Nuclear / Q000097:blood*; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood*; D014463:Ultrasonography
chemical_list: D006442:Glycated Hemoglobin; D006023:Glycoproteins; D053244:Osteoprotegerin; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C506030:TNFRSF11B protein, human