Serum osteoprotegerin, RANKL, and Dkk-1 levels in adults with Langerhans cell histiocytosis.

CONTEXT 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. DESIGN This was a cross-sectional study in an adult LCH cohort followed for 12.2 ± 2.1 yr. SETTING The study was conducted in an outpatient clinic. SUBJECTS Twenty-five adult patients with a definitive LCH diagnosis and 50 matched controls participated in the study. INTERVENTIONS Early morning, fasting, venous sampling was conducted in all subjects. MAIN OUTCOME MEASURE 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.