Selected pro-inflammatory cytokines, bone metabolism, osteoprotegerin, and receptor activator of nuclear factor-κB ligand in girls with anorexia nervosa

Introduction: It has been indicated that disturbances in the production of certain pro-inflammatory cytokines might contribute to the development of osteoporosis in girls with anorexia nervosa (AN). The aim of the study was to determine whether girls with AN exhibited a relationship between IL-1 beta, IL-6, TNF-alpha, bone turnover markers (OC and CTx), OPG, sRANKL, and the OPG/sRANKL ratio. Material and methods: Serum IL-1 beta, IL-6, TNF-alpha, OC, CTx, OPG, and sRANKL were determined by ELISA in 59 girls with AN and in 17 healthy counterparts, aged 13 to 17 years. Results: Girls with AN showed significant reduction in body weight, BMI, BMI-SDS, and Cole index compared to the controls. These changes were associated with a significant increase in IL-1 beta, IL-6, TNF-alpha, OPG, and sRANKL concentrations and a decrease in bone markers and the OPG/sRANKL ratio. Significant negative correlations were found between BMI, the Cole index and CTx, OPG (girls with AN); between BMI and OC, CTx as well as the Cole index and CTx (the control group - C); between BMI, the Cole index and IL-beta 1, IL-6, TNF-alpha, CTx in all study participants (group AN+C). The combined group AN+C also exhibited positive correlation between BMI, the Cole index, and the OPG/sRANKL ratio. Girls with AN showed positive correlations between IL-1 beta, IL-6, and CTx as well as between TNF-alpha and sRANKL whereas the correlation between TNF-alpha and the OPG/sRANKL ratio was negative (IL-6 and IL-1 beta were identified to be independent predictors of CTx, TNF-alpha and IL-6 independently predicted sRANKL while TNF-alpha, IL-6, and IL-1 beta were independent predictors of the OPG/sRANKL ratio). The control participants exhibited negative correlations between IL-1 beta and OPG and positive correlations between IL-1 beta and sRANKL (IL-1 beta was found to be an independent predictor of OPG and sRANKL). In the AN+C group, IL-1 beta correlated negatively with OC and OPG and positively with sRANKL, while IL-6 and TNF-alpha positively correlated with CTx (IL-6 and TNF-alpha turned out to be independent predictors of CTx, IL-1 beta of OPG while IL-6, TNF-alpha, and IL-1 beta were independent predictors of sRANKL and the OPG/sRANKL ratio). Conclusions: The relationship between the nutritional status and IL-1 beta, IL-6, and TNF-alpha concentrations as well as bone status indicators seems to indicate that abnormalities observed regarding the concentrations of pro-inflammatory cytokines and bone remodelling in girls with AN might result from malnutrition. Correlations between IL-1 beta, IL-6, TNF-alpha, bone markers, OPG, its ligand sRANKL, and/or the OPG/sRANKL ratio suggest potential involvement of these cytokines in the mechanism underlying the lack of the expected bone mineral density increase in adolescent girls.