title: Serum osteoprotegerin, RANKL, and Dkk-1 levels in adults with Langerhans cell histiocytosis.
abstract: BACKGROUND
  Langerhans cell histiocytosis (LCH) is a rare disease of unknown etiology with a strong evidence of immunological dysfunction secondary to cytokine dysregulation.
  
  
  OBJECTIVE
  This study aimed to evaluate serum receptor activator of nuclear factor κB ligand (RANKL), osteoprotegerin (OPG), and Dickkopf-1 (Dkk-1) levels in adult patients with LCH at various stages of the disease.
  
  
  METHODS
  This was a cross-sectional study in an adult LCH cohort followed for 12.2 ± 2.1 yr.
  
  
  METHODS
  The study was conducted in an outpatient clinic.
  
  
  METHODS
  Twenty-five adult patients with a definitive LCH diagnosis and 50 matched controls participated in the study.
  
  
  METHODS
  Early morning, fasting, venous sampling was conducted in all subjects.
  
  
  METHODS
  We compared RANKL, OPG, and Dkk-1 serum levels between patients and controls, as well as their association with disease parameters.
  
  
  RESULTS
  Serum OPG levels were significantly higher (3.0 ± 0.2 vs. 1.7 ± 0.1 pmol/liter; P < 0.001), whereas RANKL/OPG ratio was significantly lower (0.201 ± 0.041 vs. 0.471 ± 0.072; P = 0.02) in LCH patients compared to controls. Both higher OPG (adjusted odds ratio, 3.431; 95% confidence interval, 1.329-8.924) and lower RANKL (adjusted odds ratio, 0.144; 95% confidence interval, 0.034-0.605) levels were independently associated with LCH in logistic regression analysis, after adjustment for all other parameters. Dkk-1 did not differ among patients and controls.
  
  
  CONCLUSIONS
  Adults with LCH have high serum OPG levels and low serum RANKL levels. In contrast with other disorders involving the skeleton, serum Dkk-1 levels are similar between LCH patients and controls.
authors.affiliation: Department of Endocrinology and Diabetes, 251 Hellenic Air Force and Veterans General Hospital, 3 Kanellopoulou st, 115 25 Goudi, Athens, Greece. makras@internet.gr
authors.forename: Polyzois
authors.initials: P
authors.lastname: Makras
authors.forename: Stergios A
authors.initials: SA
authors.lastname: Polyzos
authors.forename: Athanasios D
authors.initials: AD
authors.lastname: Anastasilakis
authors.forename: Evangelos
authors.initials: E
authors.lastname: Terpos
authors.forename: George
authors.initials: G
authors.lastname: Kanakis
authors.forename: Marian
authors.initials: M
authors.lastname: Schini
authors.forename: Athanasios
authors.initials: A
authors.lastname: Papatheodorou
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Kaltsas
mesh_terms: D000328:Adult; D000368:Aged; D000465:Algorithms; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D005500:Follow-Up Studies; D006646:Histiocytosis, Langerhans-Cell / Q000097:blood* / Q000503:physiopathology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D053244:Osteoprotegerin / Q000097:blood*; D010044:Outpatient Clinics, Hospital; D053245:RANK Ligand / Q000097:blood*; D012008:Recurrence; D012075:Remission, Spontaneous; D055815:Young Adult
chemical_list: D015415:Biomarkers; C501126:DKK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D053244:Osteoprotegerin; D053245:RANK Ligand; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human