title: Sclerostin distribution in children and adolescents with type 1 diabetes mellitus and correlation with bone metabolism and bone mineral density.
abstract: Sclerostin is an inhibitor of the Wnt/beta-catenin bone metabolic pathway. Increased sclerostin levels and reduced bone mineral density (BMD) have been documented in adult patients with diabetes mellitus (DM), predominantly in those with type 2 diabetes mellitus (T2DM). No relative data exist on childhood type 1 diabetes mellitus (T1DM). Our objective was to study plasma sclerostin in T1DM children and adolescents and controls and its correlations with metabolic bone markers and BMD.
  
  
  
  This was a cross-sectional study that was conducted at an outpatient clinical center. Forty T1DM children and adolescents were evaluated (mean ± SD age: 13.04 ± 3.53 yr, T1DM duration: 5.15 ± 3.33 yr), along with 40 healthy matched controls (age 12.99 ± 3.3 yr). Sclerostin, soluble receptor activator of nuclear factor-kappaB ligand (s-RANKL), osteoprotegerin, osteocalcin, C-telopeptide crosslinks, electrolytes, parathyroid hormone (PTH), and total 25(OH)D were measured. Lumbar and subcranial total body BMD were evaluated with dual energy X-ray absorptiometry (DXA).
  
  
  
  Sclerostin levels demonstrated a Gaussian distribution, with no significant difference between patients and controls (51.56 ± 12.05 vs. 50.98 ± 13.55 pmol/L, p = 0.84). Significantly lower values were found in girls and prepubertal children. Sclerostin values were significantly and gradually increased in children through pubertal Tanner stages 1-3, were reduced at stage 4 and increased again at pubertal stage 5. Sclerostin levels were positively correlated with logCTX (logarithm of C-terminal telopeptide crosslinks of type I collagen), logOsteocalcin (logarithm of Osteocalcin), magnesium, total body, and L1-L4 BMD z-score.
  
  
  
  T1DM patients had similar levels of sclerostin with controls. Sclerostin correlated with bone resorption and formation markers and also with bone mass indices, gender, and pubertal stage. The decrease in sclerostin values observed in pubertal stage 4 adolescents coincides with the concurrent growth spurt, and is consistent with sclerostin physiology as an inhibiting signal.
authors.affiliation: Diabetic Clinic, 2nd Department of Pediatrics, Athens University Medical School, 'P&A Kyriakou' Children's Hospital, Athens, Greece.
authors.forename: Charalampos
authors.initials: C
authors.lastname: Tsentidis
authors.affiliation: Laboratory of Clinical Biochemistry - Molecular Diagnostics, 2nd Department of Pediatrics, Athens University Medical School, 'P & A Kyriakou' Children's Hospital, Athens, Greece.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Gourgiotis
authors.affiliation: Diabetic Clinic, 2nd Department of Pediatrics, Athens University Medical School, 'P&A Kyriakou' Children's Hospital, Athens, Greece.
authors.forename: Lydia
authors.initials: L
authors.lastname: Kossiva
authors.affiliation: Laboratory of Clinical Biochemistry - Molecular Diagnostics, 2nd Department of Pediatrics, Athens University Medical School, 'P & A Kyriakou' Children's Hospital, Athens, Greece.
authors.forename: Antonios
authors.initials: A
authors.lastname: Marmarinos
authors.affiliation: Department of Bone and Mineral Metabolism, Institute of Child Health, 'Aghia Sophia' Children's Hospital, Athens, Greece.
authors.forename: Artemis
authors.initials: A
authors.lastname: Doulgeraki
authors.affiliation: Diabetic Clinic, 2nd Department of Pediatrics, Athens University Medical School, 'P&A Kyriakou' Children's Hospital, Athens, Greece.
authors.forename: Kyriaki
authors.initials: K
authors.lastname: Karavanaki
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000293:Adolescent; D041923:Adolescent Development; D015519:Bone Density; D001846:Bone Development; D019485:Bone Morphogenetic Proteins / Q000097:blood*; D001862:Bone Resorption; D016022:Case-Control Studies; D002648:Child; D003430:Cross-Sectional Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood*; D005260:Female; D005819:Genetic Markers; D006801:Humans; D008297:Male; D010012:Osteogenesis; D060449:Wnt Signaling Pathway
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D019485:Bone Morphogenetic Proteins; D005819:Genetic Markers; C422903:SOST protein, human
keywords: adolescents; bone metabolism; children; osteopenia; sclerostin; type 1 diabetes