High Dickkopf-1 levels are associated with chronic inflammation in children with sickle cell disease

Objectives: Sickle bone disease (SBD) is a chronic complication of sickle cell disease (SCD) whose pathogenesis is not completely understood. Chronic inflammation associated with SCD could alter bone remodeling. Our aim was to analyze the serum levels of bone remodeling markers in a group of SCD children to evaluate their involvement in the SBD. Methods: We enrolled 26 SCD subjects and 26 age-matched controls, who lived in the same geographic area. DKK-1, sclerostin, RANKL, and OPG serum levels were evaluated. Neutrophil-lymphocyte ratio (NLR) was also evaluated as a marker of inflammation. Results: The analysis of bone remodeling markers did not show any significant difference between the two groups except for DKK-1 levels that were significantly higher in the patients than controls (p < .05). A significant direct correlation between NLR and DKK-1 (p = .004) was found. An inverse correlation between NLR and osteocalcin (p = .01) has also been observed. Conclusions: The chronic inflammation, which represents a peculiar characteristic in SCD patients, would represent the primary causal agent of the activation of osteoblastogenesis inhibitors responsible of bone impairment in these subjects. Further studies will be needed to better explain the role of these inhibitors in SCD, to prevent or treat bone damage in this population.